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Psychological and Physiological Trauma Research
Seize Your Journeys
_______________________ Traumatic stress is found in many competent, healthy, strong, good people. No one can completely protect themselves from traumatic experiences. Many people have long-lasting problems following exposure to trauma. Up to 8% of persons will have PTSD at some time in their lives. People who react to traumas are not going crazy. What is happening to them is part of a set of common symptoms and problems that are connected with being in a traumatic situation, and thus, is a normal reaction to abnormal events and experiences. Having symptoms after a traumatic event is NOT a sign of personal weakness. Given exposure to a trauma that is bad enough, probably all people would develop PTSD. By understanding trauma symptoms better, a person can become less fearful of them and better able to manage them. By recognizing the effects of trauma and knowing more about symptoms, a person will be better able to decide about getting treatment. _______________________
FUNCTIONAL NEUROANATOMY In order to best understand this atlas it is important to have a sense of the functional neuroanatomy of the brain. Over the next several pages there is a brief summary of the 5 major brain systems that relate to behavior, along with the general location seen on SPECT of these areas.
The Deep Limbic System
Functions
Problems
The Basal Ganglia System
Functions
Problems
The Prefrontal Cortex
Functions
Problems
The Cingulate Gyrus
Problems
The Temporal Lobes
Functions
Problems
Non-dominant Side (usually the right)
Secure Attachments as a Defense Against Trauma “All people mature and thrive in a social context that has profound effects on how they cope with life’s stresses. Particularly early in life, the social context plays a critical role in fuffering an individual against stressful situations, and in building the psychological and biological capacities to deal with further stresses. The primary function of parents can be thought of as helping children modulate their arousal by attuned and well-timed provision of playing, feeding, comforting, touching, looking, cleaning, and resting—in short, by teaching them skills that will gradually help them modulate their own arousal. Secure attachment bonds serve as primary defenses against trauma-induced psychopathology in both children and adults (Finkelhor & Browne, 1984). In children who have been exposed to severe stressors, the quality of the parental bond is probably the single most important determinant of long-term damage (McFarlane, 1988).” van der Kolk, Bessel, Alexander C. McFarlane, and Lars Weisaeth, eds. 1996. Traumatic stress: The effects of overwhelming experience on mind, body, and society. New York and London: Guilford Press. .p. 185 _______________________
Sleep Disorders
“The sleep disorders are organized into four major sections according to presumed etiology. Primary Sleep Disorders are those in which none of the etiologies listed below (i.e., another mental disorder, a general medical condition, or a substance) is responsible. Primary Sleep Disorders are presumed to arise from endogenous abnormalities in sleep-wake generating or timing mechanisms, often complicated by conditioning factors. Primary Sleep Disorders in turn are divided into Dyssomnias (characterized by abnormalities in the amount, quality, or timing of sleep) and Parasomnias (characterized by abnormal behavioral or physiological events occurring in association with sleep, specific sleep stages, or sleep-awake transitions). Sleep Disorder Related to Another Mental Disorder involves a prominent complaint of sleep disturbance that results from a diagnosable mental disorder (often a Mood Disorder or Anxiety Disorder) but that is sufficiently severe to warrant independent clinical attention. Presumably, the pathophysiological mechanisms responsible for the mental disorder also affect sleep-awake regulation. Sleep Disorder Due to a General Medical Condition involves a prominent complaint of sleep disturbance that results from the direct physiological effects of a general medical condition on the sleep-wake system. Substance-Induced Sleep Disorder involves prominent complaints of sleep disturbance that result from the concurrent use, or recent discontinuation of use, of a substance (including medications). That systematic assessment in individuals who present with prominent complaints of sleep disturbance includes an evaluation of the specific type of sleep complaint and a consideration of concurrent mental disorders, general medical conditions, and substance (including medication) use that may be responsible for the sleep disturbance. Five distinct sleep stages can be measured by polysomnography: rapid eye movement (REM) sleep and four stages of non-rapid eye movement (NREM) sleep (stages 1, 2, 3, and 4). Stage 1 NREM sleep is a transition from wakefulness to sleep and occupies about 5% of time spent asleep in healthy adults. Stage 2 NREM sleep, which is characterized by specific EEG waveforms (sleep spindles and K complexes), occupies about 50% of time spent asleep. Stages 3 and 4 NREM sleep (also known collectively as slow-wave sleep) are the deepest levels of sleep and occupy about 10%-20% of sleep time. REM sleep, during which the majority of typical storylike dreams occur, occupies about 20%-25% of total sleep. These sleep stages have a characteristic temporal organization across the night. NREM stages 3 and 4 tend to occur in the first one-third to one-half of the night and increase in duration in response to sleep deprivation. REM sleep occurs cyclically throughout the night, alternating with NREM sleep about every 80-100 minutes. REM sleep periods increase in duration toward the morning. Human sleep also varies characteristically across the life span. After relative stability with large amounts of slow-wave sleep in childhood and early adolescence, sleep continuity and depth deteriorate across the adult age range. This deterioration is reflected by increased wakefulness and stage 1 sleep and decreased stages 3 and 4 sleep. Because of this, age must be considered in the diagnosis of a Sleep Disorder in any individual. Polysomnography is the monitoring of multiple electrophysiological parameters during sleep and generally includes measurement of EEG activity, electroculographic activity, and electromyographic activity. Additional polysomnographic measures may include oral or nasal airflow, respiratory effort, chest and abdominal wall movement, oxyhemoglobin saturation, or exhaled carbon dioxide concentration; these measures are used to monitor respiration during sleep and to detect the presence and severity of sleep apnea. Measurement of peripheral electromyographic activity may be used to detect abnormal movements during sleep. Most polysomnographic studies are conducted during the person’s usual sleeping hours—that is, at night. However, daytime polysomnographic studies also are used to quantify daytime sleepiness. The most common daytime procedure is the Multiple Sleep Latency Test (MSLT), in which the individual is instructed to lie down in a dark room and not resist falling asleep; this protocol is repeated fives times during the day. Sleep latency (the amount of time required to fall asleep) is measured on each trial and is used as an index of physiological sleepiness. The converse of the MSLT is also used: In the Repeated Test of Sustained Wakefulness (RTSW), the individual is placed in a quiet, dimly lit room and instructed to remain awake; this protocol is repeated several times during the day. Again, sleep latency is measured, but is it used here as an index of the individual’s ability to maintain wakefulness. Standard terminology for polysomnographic measures is used throughout the test in this section. Sleep continuity refers to the overall balance of sleep and wakefulness during a night of sleep. “Better” sleep continuity indicates consolidated sleep and wakefulness; “worse” sleep continuity indicates disrupted sleep with more wakefulness. Specific sleep continuity measures include sleep latency—the amount of time required to fall asleep (expressed in minutes); intermittent wakefulness—the amount of awake time after initial sleep onset (expressed in minutes); and sleep efficiency—the ratio of actual time spent asleep to time spent in bed (expressed as a percentage, with higher numbers indicating better sleep continuity). Sleep architecture refers to the amount and distribution of specific sleep stages. Sleep architecture measures include absolute amount of REM sleep and each NREM sleep stage (in minutes), relative amount of REM seep and NREM sleep stages (expressed as a percentage of total sleep time), and latency between sleep onset and the first REM period (REM latency). The text for each of the Sleep Disorders contains a section describing its relationship to corresponding disorders in The International Classification of Sleep Disorders: (ICSD) diagnostic and Coding Manual, published in 1990 by the American Sleep Disorders Association. _________________
Substance Dependence “Features The essential feature of Substance Dependence is a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues use of the substance despite significant substance-related problems. There is a pattern of repeated self-administration that can result in tolerance, withdrawal, and compulsive drug-taking behavior. A diagnosis of Substance Dependence can be applied to every class of substances except caffeine. The symptoms of Dependence are similar across the various categories of substances, but for certain classes some symptoms are less salient, and in a few instances not all symptoms apply (e.g., withdrawal symptoms are not specified for Hallucinogenic Dependence). Although not specifically listed as a criterion item, “craving” (a strong subjective drive to use the substance) is likely to be experienced by most (if not all) individuals with Substance Dependence. Dependence is defined as a cluster of three or more of the symptoms listed below occurring at any time in the same 12-month-period. Tolerance (Criterion 1) is the need for greatly increased amounts of the substance to achieve intoxication (or the desired effect) or a markedly diminished effect with continued use of the same amount of the substance. The degree to which tolerance develops varies greatly across substances. Furthermore, for a specific drug, varied degrees of tolerance may develop for its different central nervous system effects. For example, for opioids, tolerance to respiratory depression and tolerance to analgesia develop at different rates. Individuals with heavy use of opioids and stimulants can develop substantial (e.g., 10-f0ld) levels of tolerance, often to a dosage that would be lethal to a nonuser. Alcohol tolerance can also be pronounced, but is usually less extreme than for amphetamine. Many individuals who smoke cigarettes consume more than 20 cigarettes a day, an amount that would have produced symptoms of toxicity when they first started smoking. Individuals with heavy use of cannabis or phencyclidine (PCP) are generally not aware of having developed tolerance (although it has been demonstrated in animal studies and in some individuals). Tolerance may be difficult to determine by history alone when the substance used is illegal and perhaps mixed with various diluents or with other substances. In such situations, laboratory tests may be helpful (e.g., high blood levels of the substance coupled with little evidence of intoxication suggest that tolerance is likely). Tolerance must also be distinguished from individual variability in the initial sensitivity to the effects of particular substances. For example, some first-time drinkers show very little evidence of intoxication with three or four drink, whereas others of similar weight and drinking histories had slurred speech and incoordination. Withdrawal (Criterion 2a) is a maladaptive behavioral change, with physiological and cognitive concomitants, that occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance. After developing unpleasant withdrawal symptoms, the persons is likely to take the substance to relieve or to avoid those symptoms (Criterion 2b), typically using the substance throughout the day beginning soon after awakening. Withdrawal symptoms, which are generally the opposite of the acute effects of the substance, vary greatly across the calluses of substances, and separate criteria sets for Withdrawal are provided for most of the classes. Marked and generally easily measured physiological signs of withdrawal are common with alcohol, opioids, and sedatives, hypnotics, and anxiolytics. Withdrawal signs and symptoms are often present, but may be less apparent, with stimulants such as amphetamines and cocaine, as well as with nicotine and cannabis. No significant withdrawal is seen even after repeated use of hallucinogens. Withdrawal from phencyclidine and related substances has not yet been described in humans (although it has been demonstrated in animals). Neither tolerance nor withdrawal is necessary or sufficient for a diagnosis of Substance Dependence. However, for most classes of substances, a past history of tolerance or withdrawals is associated with a more severe clinical course (i.e., an earlier onset of Dependence, higher levels of substance intake, and a greater number of substance-related problems). Some individuals (e.g., those with Cannabis Dependence) show a pattern of compulsive use without obvious signs of tolerance or withdrawal. Conversely, some general medical and postsurgical patients without Opioid Dependence may develop a tolerance to prescribed opioids and experience withdrawal symptoms without showing any signs of compulsive use. The specifiers With Physiological Dependence and Without Physiological Dependence are provided to indicate the presence or absence of tolerance or withdrawal. The following items describe the pattern of compulsive substance use that is characteristic of Dependence. The individual may take the substance in larger amounts or over a longer period than was originally intended (e.g., continuing to drink until severely intoxicated despite having set a limit of only one drink) (Criterion 3). The individual may express a persistent desire to cut down or regulate substance use. Often, there have been many unsuccessful efforts to decrease or discontinue use (Criterion 4). The individual may spend a great deal of time obtaining the substance, using the substance, or recovering from its effects (Criterion 5). In some instances of Substance Dependence, virtually all of the person’s daily activities revolve around the substance. Important social, occupational, ore recreational activities may be given up or reduced because of substance use (Criterion 6). The individual may withdraw from family activities and hobbies in order to use the substance in private or to spend more time with substance-using friends. Despite recognizing the contributing role of the substance to a psychological or physical problem (e.g., sever depressive symptoms or damage to organ systems), the person continues to use the substance (Criterion 7). The key issue in evaluating this criterion is not eh existence of the problem, but rather the individual’s failure to abstain from using the substance despite having evidence of the difficulty it is causing.
Specifiers Tolerance and withdrawal may be associated with a higher risk for immediate general medical problems and a higher relapse rate. Specifiers are provided to note their presence or absence: With Physiological Dependence. This specifier should be used when Substance Dependence is accompanied by evidence of tolerance (Criterion 1) or withdrawal (Criterion 2). Without Physiological Dependence. This specifier should be used when there is no evidence of tolerance (Criterion 1) or withdrawal (Criterion 2). In these individuals, Substance Dependence is characterized by a pattern of compulsive use (at least three items from Criteria 3-7).”
Diagnostic and Statistical Manual of Mental Disorders. 2000. 4th ed. Washington, D.C.: American Psychiatric Association. P. 193-195.
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PTSD, DID, and EMDR Posttraumatic Stress Disorder "The essential feature of Posttraumatic Stress Disorder us the development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an event that involves actual or threatened death or serious injury, or other threat to one's physical integrity; or witnessing an event that involves death, injury, or a threat to the physical integrity of another person; or learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or other close associate (Criteria A1). The person's response to the event must involve intense fear, helplessness, or horror (or in children, the response must involve disorganized or agitated behavior) (Criterion A2). The characteristic symptoms resulting from the exposure to the extreme trauma include persistent reexperiencing of the traumatic event (Criterion E), and the disturbance must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion F). Traumatic events that are experienced directly include, but are not limited to, military combat, violent personal assault (sexual assault, physical attack, robbery, mugging), being kidnapped, being taken hostage, terrorist attack, torture, incarceration as a prisoner of war or in a concentration camp, natural or manmade disasters, severe automobile accidents, or being diagnosed with a life-threatening illness. For children, sexually traumatic events may include developmentally inappropriate sexual experiences without threatened or actual violence or injury. Witnessed events include, but are not limited to, observing the serious injury or unnatural death of another person due to violent assault, accident, war, or disaster or unexpectedly witnessing a dead body or body parts. Events experienced by others that are learned about include, but are not limited to, violent personal assault, serious accident, or serious injury experienced y a family member or a close friend; learning about the sudden, unexpected death of a family member or a close friend; or learning that one's child has a life threatening disease. The disorder may be especially sever or long lasting when the stressor is of human design (e.g., torture, rape). the likelihood of developing this disorder may increase as the intensity of and physical proximity to the stressor increase. The traumatic event can be reexperienced in various ways. Commonly the person has recurrent and intrusive recollections of the event (Criterion B1) or recurrent distressing dreams during which the event can be replayed or otherwise represented (Criterion B2). In rare instances, the person experiences dissociative states that last from a few seconds to several hours, or even days, during which components of the event are relived and the person behaves as though experiencing the event at that moment (Criterion B3). These episodes, often referred to as "flashbacks," are typically brief but can be associated with prolonged distress and heightened arousal. Intense psychological distress (Criterion B4) or physiological reactivity (Criterion B5) often occurs when the person is exposed to triggering events that resemble or symbolize an aspect of the traumatic event (e.g., anniversaries of the traumatic event; cold, snowy weather or uniformed guards for survivors of death camps in cold climates; hot, humid weather for combat veterans of the South Pacific; entering any elevator for an woman who was reaped in an elevator). Stimuli associated with the trauma are persistently avoided. The person commonly makes deliberate efforts to avoid thoughts, feelings, or conversations about the traumatic event (Criterion C1) and to avoid activities, situations, or people who around recollections of it (Criterion C2). This avoidance of reminders may include amnesia for an important aspect of the traumatic event (Criterion C3). Diminished responsiveness to the external work, referred to as "psychic numbing" or "emotional anesthesia," usually begins soon after the traumatic event. The individual may complain of having markedly diminished interest or participation in previously enjoyed activities (Criterion C4), of feeling detached or estranged from other people (Criterion C5), or of having markedly reduced ability to feel emotions (especially those associated with intimacy, tenderness and sexuality) (Criterion C6). The individual may have a sense of a foreshortened future (e.g., not expecting to have a career, marriage, children, or a normal life span) (Criterion C7). The individual has persistent symptoms of anxiety or increased arousal that were not present before the trauma. these symptoms may include difficulty falling or staying asleep that may be to recurrent nightmares during which the traumatic event is relived (Criterion D1), hypervigilance (Criterion D4), and exaggerated startle response (Criterion D5). Some individuals report irritability or outburst of anger (Criterion D2) or difficulty concentrating or completing tasks (Criterion D3)."
Dissociative Identity Disorder (DID) "The essential feature of Dissociative identity Disorder is the presence of two or more distinct identities or personality states (Criterion A) that recurrently take control of behavior (Criterion B). There is an inability to recall important personal information, the extent of which is too great to be explained by ordinary forgetfulness (Criterion C). The disturbance is not due tot eh direct physiological effects of a substance or a general medical condition (Condition D.). In children, the symptoms cannot be attributed to imaginary playmates or other fantasy play. Dissociative Identity Disorder reflects a failure to integrate various aspects of identity, memory, and consciousness. Each personality state may be experienced as if it has a distinct personal history, self-image, and identity, including a separate name. Usually there is a primary identity that carries the individual's given name and is passive, dependent, guilty, and depressed. The alternate identities frequently have different names and characteristics that contrast with the primary identity (e.g., are hostile, controlling, and self-destructive). Particular identities may emerge in specific circumstances and may differ in reported age and gender, vocabulary, general knowledge, or predominant affect. Alternate identities are experienced as taking control in sequence, ore at the expense of the other, and may deny knowledge of one another, be critical of one another, or appear to be in open conflict. Occasionally, one or more powerful identities allocate time to the others. Aggressive or hostile identities may at times interrupt activities or place the others in uncomfortable situations. Individuals with this disorder experience frequent gaps in memory for personal history, both remote and recent. The amnesia is frequently asymmetrical. The more passive identities tend to have more constricted memories, whereas the more hostile, controlling, or "protector" identities have more complete memories. An identity that is not in control may nonetheless gain access to consciousness by producing auditory or visual hallucinations (e.g., a voice giving instructions). Evidence of amnesia may be uncovered by reports from others who have witnessed behavior that is disavowed by the individual or by the individual's own discoveries (e.g., finding items of clothing at home that the individual cannot remember having bought). There may be loss of memory not only for recurrent periods of time, but also an overall loss of biographical memory for some extended period of childhood, adolescence, or even adulthood. Transitions among identities are often triggered by psychosocial stress. The time required to switch from one identity to another is usually a matter of seconds, but, less frequently, may b gradual. Behavior that may be frequently associated with identity switches include rapid blinking, facial changes, changes in voice or demeanor, or disruption in the individual's train of thoughts. The number of identities reported ranges from 2 to more than 100. Half of reported cases include the individuals with 10 or fewer identities." Diagnostic and Statistical Manual of Mental Disorders. 2000. 4th ed. Washington, D.C.: American Psychiatric Association. EMDR Eye Movement Desensitization and Reprocessing "Eye Movement Desensitization and Reprocessing (EMDR)1 integrates elements of many effective psychotherapies in structured protocols that are designed to maximize treatment effects. These include psychodynamic, cognitive behavioral, interpersonal, experiential, and body-centered therapies2. EMDR is an information processing therapy and uses an eight phase approach. During EMDR1 the client attends to past and present experiences in brief sequential doses while simultaneously focusing on an external stimulus. Then the client is instructed to let new material become the focus of the next set of dual attention. This sequence of dual attention and personal association is repeated many times in the session. Eight Phases of Treatment The first phase is a history taking session during which the therapist assesses the client's readiness for EMDR and develops a treatment plan. Client and therapist identify possible targets for EMDR processing. These include recent distressing events, current situations that elicit emotional disturbance, related historical incidents, and the development of specific skills and behaviors that will be needed by the client in future situations. During the second phase of treatment, the therapist ensures that the client has adequate methods of handling emotional distress and good coping skills, and that the client is in a relatively stable state. If further stabilization is required, or if additional skills are needed, therapy focuses on providing these. The client is then able to use stress reducing techniques whenever necessary, during or between sessions. However, one goal is not to need these techniques once therapy is complete. In phase three through six, a target is identified and processed using EMDR procedures. These involve the client identifying the most vivid visual image related to the memory (if available), a negative belief about self, related emotions and body sensations. The client also identifies a preferred positive belief. The validity of the positive belief is rated, as is the intensity of the negative emotions. After this, the client is instructed to focus on the image, negative thought, and body sensations while simultaneously moving his/her eyes back and forth following the therapist's fingers as they move across his/her field of vision for 20-30 seconds or more, depending upon the need of the client. Athough eye movements are the most commonly used external stimulus, therapists often use auditory tones, tapping, or other types of tactile stimulation. The kind of dual attention and the length of each set is customized to the need of the client. The client is instructed to just notice whatever happens. After this, the clinician instructs the client to let his/her mind go blank and to notice whatever thought, feeling, image, memory, or sensation comes to mind. Depending upon the client's report the clinician will facilitate the next focus of attention. In most cases a client-directed association process is encouraged. This is repeated numerous times throughout the session. If the client becomes distressed or has difficulty with the process, the therapist follows established procedures to help the client resume processing. When the client reports no distress related to the targeted memory, the clinician asks him/her to think of the preferred positive belief that was identified at the beginning of the session, or a better one if it has emerged, and to focus on the incident, while simultaneously engaging in the eye movements. After several sets, clients generally report increased confidence in this positive belief. The therapist checks with the client regarding body sensations. If there are negative sensations, these are processed as above. If there are positive sensations, they are further enhanced. In phase seven, closure, the therapist asks the client to keep a journal during the week to document any related material that may arise and reminds the client of the self-calming activities that were mastered in phase two. The next session begins with phase eight, re-evaluation of the previous work, and of progress since the previous session. EMDR treatment ensures processing of all related historical events, current incidents that elicit distress, and future scenarios that will require different responses. The overall goal is produce the most comprehensive and profound treatment effects in the shortest period of time, while simultaneously maintaining a stable client within a balanced system. After EMDR processing, clients generally report that the emotional distress related to the memory has been eliminated, or greatly decreased, and that they have gained important cognitive insights. Importantly, these emotional and cognitive changes usually result in spontaneous behavioral and personal change, which are further enhanced with standard EMDR procedures." www.emdr.com __________________ Major Depressive Disorder “Diagnostic Features The essential feature of Major Depressive Disorder is a clinical course that is characterized by one or more Major Depressive Episodes without a history of Manic, Mixed, or Hypomanic Episodes (Criteria A and C). Episodes of Substance-Induced Mood Disorder (due to the direct physiological effects of a drug of abuse, a medication, or toxin exposure) or of Mood Disorder Due to a General Medical Condition do not count toward a diagnosis of Major Depressive Disorder. In addition, the episodes must not be better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified (Criterion B). The fourth digit in the diagnostic code for Major Depressive Disorder indicates whether it is a Single Episode (used only for first episodes) or Recurrent. It is sometimes difficult to distinguish between a single episode with waxing and waning symptoms and two separate episodes. For purposes of this manual, an episode is considered to have ended when the full criteria for eh Major Depressive Episode have not been met for at least 2 consecutive months. During this 2-month period, there is either complete resolution of symptoms or the presence of depressive symptoms that no longer meet the full criteria for a Major Depressive Episode (In Partial Remission). The fifth digit in the diagnostic code for Major Depressive Disorder indicates the current state of the disturbance. If the criteria for a Major Depressive Disorder are met, the severity of the episode is notes as Mild, Moderate, Severe Without Psychotic Features, or Severe With Psychotic Features. If the criteria for a Major Depressive Episode are not currently met, the fifth digit is used to indicate whether the disorder is In Partial Remission or In Full Remission. If Manic, Mixed, or Hypomanic Episodes develop in the course of Major Depressive Disorder, the diagnosis is changed to a Bipolar Disorder. However, if manic or hypomanic symptoms occur as a direct effect of antidepressant treatment, use of other medications, substance use, or toxin exposure, the diagnosis of Major Depressive Disorder remains appropriate and an addition diagnosis of Substance-induced Mood Disorder, With Manic features (or With Mixed Features), should be noted. Similarly, if manic or hypomanic symptoms occur as a direct effect of a general medical condition, the diagnosis of Major Depressive Disorder remains appropriate and an additional diagnosis of Mood Disorder Due to a General Medical Condition, With Manic Features (or With Mixed Features), should be noted.” p. 369 “Course Major Depressive Disorder may begin at any age, with an average age at onset in the mid-20s. Epidemiological data suggest that the age at onset is decreasing for those born more recently. The course of Major Depressive Disorder, Recurrent, is variable. Some people have isolated episodes that are separated by many years without any depressive symptoms, whereas others have clusters of episodes, and still others have increasingly frequent episodes as they grow older. Some evidence suggests that the periods of remission generally last longer early in the course of the disorder. The number of prior episodes predicts the likelihood of developing a subsequent Major Depressive Episode. At least 60% of individuals with Major Depresssive Disorder, Single Episode, can be expected to have a second episode. Individuals who have had tow episodes have a 70% chance of having a third, and individuals who have had three episodes have a 90% chance of having a fourth. About 5%-10% of individuals with Major Depressive Disorder, single Episode, subsequently develop a Manic Episode (i.e., develop Bipolar I Disorder). Major Depressive Episodes may end completely (in about two-thirds of cases), or only partially or not at all (in about one-third of cases). For individuals who have only partial remission, there is a greater likelihood of developing additional episodes and of continuing the pattern of partial interepisode recovery. The longitudinal course specifiers With Full Interepisode Recovery and Without Full Interepisode Recovery may therefore have prognostic value. A number of individuals have pre-existing Dysthymic Disorder prior to the onset of Major Depressive Disorder, single Episode. Some evidence suggests that these individuals are more likely to have additional Major Depressive Episodes, have poorer interepisode recovery, and may require additional acute-phase treatment and a longer period of continuing treatment to attain and maintain a more thorough and longer-lasting euthymic state. Follow-up naturalistic studies suggested that 1 year after the diagnosis of a major Depressive Episode, 40% of individuals still have symptoms that are sufficiently severe to meet criteria for a full Major Depressive Episode, roughly 20% continue to have some symptoms that no longer meet full criteria for a Major Depressive Episode (i.e., major Depressive Disorder, In Partial Remission), and 40% have no Mood Disorder. The severity of the initial Major Depressive Episode appears to predict persistence. Chronic general medical conditions are also a risk factor for more persistent episodes. Episodes of Major Depressive Disorder often follow a severe psychosocial stressor, such as the death of a loved one or divorce. Studies suggest that psychosocial events 9stressors) may play a more significant role in the precipitation of the first or second episodes of Major Depressive Disorder and may play less of a role in the onset of subsequent episodes. Chronic general medical conditions and Substance Dependence (particularly Alcohol or Cocaine Dependence) may contribute to the onset or exacerbation of Major Depressive Disorder. It is difficult to predict whether the first episode of a Major Depressive Disorder in a young person will ultimately evolve into a Bipolar Disorder. Some data suggest that the acute onset of severe depression, especially with psychotic features and psychomotor retardation, in a young person without prepubertal psychopathology is more likely to predict a bipolar disorder. A family history of Bipolar Disorder may also be suggestive of subsequent development of Bipolar Disorder.” p. 372-373
Diagnostic and statistical manual of mental disorders. 2000. 4th ed. Washington, D.C.: American Psychiatric Association.
________________ Major Depressive Disorder “Diagnostic Features The essential feature of Major Depressive Disorder is a clinical course that is characterized by one or more Major Depressive Episodes without a history of Manic, Mixed, or Hypomanic Episodes (Criteria A and C). Episodes of Substance-Induced Mood Disorder (due to the direct physiological effects of a drug of abuse, a medication, or toxin exposure) or of Mood Disorder Due to a General Medical Condition do not count toward a diagnosis of Major Depressive Disorder. In addition, the episodes must not be better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified (Criterion B). The fourth digit in the diagnostic code for Major Depressive Disorder indicates whether it is a Single Episode (used only for first episodes) or Recurrent. It is sometimes difficult to distinguish between a single episode with waxing and waning symptoms and two separate episodes. For purposes of this manual, an episode is considered to have ended when the full criteria for eh Major Depressive Episode have not been met for at least 2 consecutive months. During this 2-month period, there is either complete resolution of symptoms or the presence of depressive symptoms that no longer meet the full criteria for a Major Depressive Episode (In Partial Remission). The fifth digit in the diagnostic code for Major Depressive Disorder indicates the current state of the disturbance. If the criteria for a Major Depressive Disorder are met, the severity of the episode is notes as Mild, Moderate, Severe Without Psychotic Features, or Severe With Psychotic Features. If the criteria for a Major Depressive Episode are not currently met, the fifth digit is used to indicate whether the disorder is In Partial Remission or In Full Remission. If Manic, Mixed, or Hypomanic Episodes develop in the course of Major Depressive Disorder, the diagnosis is changed to a Bipolar Disorder. However, if manic or hypomanic symptoms occur as a direct effect of antidepressant treatment, use of other medications, substance use, or toxin exposure, the diagnosis of Major Depressive Disorder remains appropriate and an addition diagnosis of Substance-induced Mood Disorder, With Manic features (or With Mixed Features), should be noted. Similarly, if manic or hypomanic symptoms occur as a direct effect of a general medical condition, the diagnosis of Major Depressive Disorder remains appropriate and an additional diagnosis of Mood Disorder Due to a General Medical Condition, With Manic Features (or With Mixed Features), should be noted.” p. 369 “Course Major Depressive Disorder may begin at any age, with an average age at onset in the mid-20s. Epidemiological data suggest that the age at onset is decreasing for those born more recently. The course of Major Depressive Disorder, Recurrent, is variable. Some people have isolated episodes that are separated by many years without any depressive symptoms, whereas others have clusters of episodes, and still others have increasingly frequent episodes as they grow older. Some evidence suggests that the periods of remission generally last longer early in the course of the disorder. The number of prior episodes predicts the likelihood of developing a subsequent Major Depressive Episode. At least 60% of individuals with Major Depresssive Disorder, Single Episode, can be expected to have a second episode. Individuals who have had tow episodes have a 70% chance of having a third, and individuals who have had three episodes have a 90% chance of having a fourth. About 5%-10% of individuals with Major Depressive Disorder, single Episode, subsequently develop a Manic Episode (i.e., develop Bipolar I Disorder). Major Depressive Episodes may end completely (in about two-thirds of cases), or only partially or not at all (in about one-third of cases). For individuals who have only partial remission, there is a greater likelihood of developing additional episodes and of continuing the pattern of partial interepisode recovery. The longitudinal course specifiers With Full Interepisode Recovery and Without Full Interepisode Recovery may therefore have prognostic value. A number of individuals have pre-existing Dysthymic Disorder prior to the onset of Major Depressive Disorder, single Episode. Some evidence suggests that these individuals are more likely to have additional Major Depressive Episodes, have poorer interepisode recovery, and may require additional acute-phase treatment and a longer period of continuing treatment to attain and maintain a more thorough and longer-lasting euthymic state. Follow-up naturalistic studies suggested that 1 year after the diagnosis of a major Depressive Episode, 40% of individuals still have symptoms that are sufficiently severe to meet criteria for a full Major Depressive Episode, roughly 20% continue to have some symptoms that no longer meet full criteria for a Major Depressive Episode (i.e., major Depressive Disorder, In Partial Remission), and 40% have no Mood Disorder. The severity of the initial Major Depressive Episode appears to predict persistence. Chronic general medical conditions are also a risk factor for more persistent episodes. Episodes of Major Depressive Disorder often follow a severe psychosocial stressor, such as the death of a loved one or divorce. Studies suggest that psychosocial events 9stressors) may play a more significant role in the precipitation of the first or second episodes of Major Depressive Disorder and may play less of a role in the onset of subsequent episodes. Chronic general medical conditions and Substance Dependence (particularly Alcohol or Cocaine Dependence) may contribute to the onset or exacerbation of Major Depressive Disorder. It is difficult to predict whether the first episode of a Major Depressive Disorder in a young person will ultimately evolve into a Bipolar Disorder. Some data suggest that the acute onset of severe depression, especially with psychotic features and psychomotor retardation, in a young person without prepubertal psychopathology is more likely to predict a bipolar disorder. A family history of Bipolar Disorder may also be suggestive of subsequent development of Bipolar Disorder.” p. 372-373 Diagnostic and statistical manual of mental disorders. 2000. 4th ed. Washington, D.C.: American Psychiatric Association. ________________ DID-PTSD-EMDR Dissociative Identity Disorder (DID) "The essential feature of Dissociative identity Disorder is the presence of two or more distinct identities or personality states (Criterion A) that recurrently take control of behavior (Criterion B). There is an inability to recall important personal information, the extent of which is too great to be explained by ordinary forgetfulness (Criterion C). The disturbance is not due tot eh direct physiological effects of a substance or a general medical condition (Condition D.). In children, the symptoms cannot be attributed to imaginary playmates or other fantasy play. Dissociative Identity Disorder reflects a failure to integrate various aspects of identity, memory, and consciousness. Each personality state may be experienced as if it has a distinct personal history, self-image, and identity, including a separate name. Usually there is a primary identity that carries the individual's given name and is passive, dependent, guilty, and depressed. The alternate identities frequently have different names and characteristics that contrast with the primary identity (e.g., are hostile, controlling, and self-destructive). Particular identities may emerge in specific circumstances and may differ in reported age and gender, vocabulary, general knowledge, or predominant affect. Alternate identities are experienced as taking control in sequence, ore at the expense of the other, and may deny knowledge of one another, be critical of one another, or appear to be in open conflict. Occasionally, one or more powerful identities allocate time to the others. Aggressive or hostile identities may at times interrupt activities or place the others in uncomfortable situations. Individuals with this disorder experience frequent gaps in memory for personal history, both remote and recent. The amnesia is frequently asymmetrical. The more passive identities tend to have more constricted memories, whereas the more hostile, controlling, or "protector" identities have more complete memories. An identity that is not in control may nonetheless gain access to consciousness by producing auditory or visual hallucinations (e.g., a voice giving instructions). Evidence of amnesia may be uncovered by reports from others who have witnessed behavior that is disavowed by the individual or by the individual's own discoveries (e.g., finding items of clothing at home that the individual cannot remember having bought). There may be loss of memory not only for recurrent periods of time, but also an overall loss of biographical memory for some extended period of childhood, adolescence, or even adulthood. Transitions among identities are often triggered by psychosocial stress. The time required to switch from one identity to another is usually a matter of seconds, but, less frequently, may b gradual. Behavior that may be frequently associated with identity switches include rapid blinking, facial changes, changes in voice or demeanor, or disruption in the individual's train of thoughts. The number of identities reported ranges from 2 to more than 100. Half of reported cases include the individuals with 10 or fewer identities." Diagnostic and Statistical Manual of Mental Disorders. 2000. 4th ed. Washington, D.C.: American Psychiatric Association. PTSD, DID, and EMDR Posttraumatic Stress Disorder "The essential feature of Posttraumatic Stress Disorder us the development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an event that involves actual or threatened death or serious injury, or other threat to one's physical integrity; or witnessing an event that involves death, injury, or a threat to the physical integrity of another person; or learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or other close associate (Criteria A1). The person's response to the event must involve intense fear, helplessness, or horror (or in children, the response must involve disorganized or agitated behavior) (Criterion A2). The characteristic symptoms resulting from the exposure to the extreme trauma include persistent reexperiencing of the traumatic event (Criterion E), and the disturbance must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion F). Traumatic events that are experienced directly include, but are not limited to, military combat, violent personal assault (sexual assault, physical attack, robbery, mugging), being kidnapped, being taken hostage, terrorist attack, torture, incarceration as a prisoner of war or in a concentration camp, natural or manmade disasters, severe automobile accidents, or being diagnosed with a life-threatening illness. For children, sexually traumatic events may include developmentally inappropriate sexual experiences without threatened or actual violence or injury. Witnessed events include, but are not limited to, observing the serious injury or unnatural death of another person due to violent assault, accident, war, or disaster or unexpectedly witnessing a dead body or body parts. Events experienced by others that are learned about include, but are not limited to, violent personal assault, serious accident, or serious injury experienced y a family member or a close friend; learning about the sudden, unexpected death of a family member or a close friend; or learning that one's child has a life threatening disease. The disorder may be especially sever or long lasting when the stressor is of human design (e.g., torture, rape). the likelihood of developing this disorder may increase as the intensity of and physical proximity to the stressor increase. The traumatic event can be reexperienced in various ways. Commonly the person has recurrent and intrusive recollections of the event (Criterion B1) or recurrent distressing dreams during which the event can be replayed or otherwise represented (Criterion B2). In rare instances, the person experiences dissociative states that last from a few seconds to several hours, or even days, during which components of the event are relived and the person behaves as though experiencing the event at that moment (Criterion B3). These episodes, often referred to as "flashbacks," are typically brief but can be associated with prolonged distress and heightened arousal. Intense psychological distress (Criterion B4) or physiological reactivity (Criterion B5) often occurs when the person is exposed to triggering events that resemble or symbolize an aspect of the traumatic event (e.g., anniversaries of the traumatic event; cold, snowy weather or uniformed guards for survivors of death camps in cold climates; hot, humid weather for combat veterans of the South Pacific; entering any elevator for an woman who was reaped in an elevator). Stimuli associated with the trauma are persistently avoided. The person commonly makes deliberate efforts to avoid thoughts, feelings, or conversations about the traumatic event (Criterion C1) and to avoid activities, situations, or people who around recollections of it (Criterion C2). This avoidance of reminders may include amnesia for an important aspect of the traumatic event (Criterion C3). Diminished responsiveness to the external work, referred to as "psychic numbing" or "emotional anesthesia," usually begins soon after the traumatic event. The individual may complain of having markedly diminished interest or participation in previously enjoyed activities (Criterion C4), of feeling detached or estranged from other people (Criterion C5), or of having markedly reduced ability to feel emotions (especially those associated with intimacy, tenderness and sexuality) (Criterion C6). The individual may have a sense of a foreshortened future (e.g., not expecting to have a career, marriage, children, or a normal life span) (Criterion C7). The individual has persistent symptoms of anxiety or increased arousal that were not present before the trauma. these symptoms may include difficulty falling or staying asleep that may be to recurrent nightmares during which the traumatic event is relived (Criterion D1), hypervigilance (Criterion D4), and exaggerated startle response (Criterion D5). Some individuals report irritability or outburst of anger (Criterion D2) or difficulty concentrating or completing tasks (Criterion D3)."
EMDR Eye Movement Desensitization and Reprocessing "Eye Movement Desensitization and Reprocessing (EMDR)1 integrates elements of many effective psychotherapies in structured protocols that are designed to maximize treatment effects. These include psychodynamic, cognitive behavioral, interpersonal, experiential, and body-centered therapies2. EMDR is an information processing therapy and uses an eight phase approach. During EMDR1 the client attends to past and present experiences in brief sequential doses while simultaneously focusing on an external stimulus. Then the client is instructed to let new material become the focus of the next set of dual attention. This sequence of dual attention and personal association is repeated many times in the session. Eight Phases of Treatment The first phase is a history taking session during which the therapist assesses the client's readiness for EMDR and develops a treatment plan. Client and therapist identify possible targets for EMDR processing. These include recent distressing events, current situations that elicit emotional disturbance, related historical incidents, and the development of specific skills and behaviors that will be needed by the client in future situations. During the second phase of treatment, the therapist ensures that the client has adequate methods of handling emotional distress and good coping skills, and that the client is in a relatively stable state. If further stabilization is required, or if additional skills are needed, therapy focuses on providing these. The client is then able to use stress reducing techniques whenever necessary, during or between sessions. However, one goal is not to need these techniques once therapy is complete. In phase three through six, a target is identified and processed using EMDR procedures. These involve the client identifying the most vivid visual image related to the memory (if available), a negative belief about self, related emotions and body sensations. The client also identifies a preferred positive belief. The validity of the positive belief is rated, as is the intensity of the negative emotions. After this, the client is instructed to focus on the image, negative thought, and body sensations while simultaneously moving his/her eyes back and forth following the therapist's fingers as they move across his/her field of vision for 20-30 seconds or more, depending upon the need of the client. Athough eye movements are the most commonly used external stimulus, therapists often use auditory tones, tapping, or other types of tactile stimulation. The kind of dual attention and the length of each set is customized to the need of the client. The client is instructed to just notice whatever happens. After this, the clinician instructs the client to let his/her mind go blank and to notice whatever thought, feeling, image, memory, or sensation comes to mind. Depending upon the client's report the clinician will facilitate the next focus of attention. In most cases a client-directed association process is encouraged. This is repeated numerous times throughout the session. If the client becomes distressed or has difficulty with the process, the therapist follows established procedures to help the client resume processing. When the client reports no distress related to the targeted memory, the clinician asks him/her to think of the preferred positive belief that was identified at the beginning of the session, or a better one if it has emerged, and to focus on the incident, while simultaneously engaging in the eye movements. After several sets, clients generally report increased confidence in this positive belief. The therapist checks with the client regarding body sensations. If there are negative sensations, these are processed as above. If there are positive sensations, they are further enhanced. In phase seven, closure, the therapist asks the client to keep a journal during the week to document any related material that may arise and reminds the client of the self-calming activities that were mastered in phase two. The next session begins with phase eight, re-evaluation of the previous work, and of progress since the previous session. EMDR treatment ensures processing of all related historical events, current incidents that elicit distress, and future scenarios that will require different responses. The overall goal is produce the most comprehensive and profound treatment effects in the shortest period of time, while simultaneously maintaining a stable client within a balanced system. After EMDR processing, clients generally report that the emotional distress related to the memory has been eliminated, or greatly decreased, and that they have gained important cognitive insights. Importantly, these emotional and cognitive changes usually result in spontaneous behavioral and personal change, which are further enhanced with standard EMDR procedures." www.emdr.com
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NeuroBiology of Trauma
Amygdala and Fear
Title: Amygdala Activation to Sad Pictures During High-Field (4 Tesla) Functional Magnetic Resonance Imaging. Author(s): Wang, Lihong, Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, US; McCarthy, Gregory, Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, US; Song, Allen W., Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, US; LaBar, Kevin S., Center for Cognitive Neuroscience, Duke University, Durham, NC, US, klabar@duke.edu Address: LaBar, Kevin S., Center for Cognitive Neuroscience, Duke University, Box 90999, Durham, NC, US, klabar@duke.edu Source: Emotion, Vol 5(1), Mar 2005. pp. 12-22. Publisher: US: American Psychological Assn Abstract: Fear-related processing in the amygdala has been well documented, but its role in signaling other emotions remains controversial. The authors recovered signal loss in the amygdala at high-field strength using an inward spiral pulse sequence and probed its response to pictures varying in their degree of portrayed sadness. These pictures were presented as intermittent task-irrelevant distractors during a concurrent visual oddball task. Relative to neutral distractors, sad distractors elicited greater activation along ventral brain regions, including the amygdala, fusiform gyrus, and inferior frontal gyrus. In contrast, oddball targets engaged dorsal sectors of frontal, parietal, and cingulate cortices. The amygdala's role in emotional evaluation thus extends to images of grief and despair as well as to those depicting violence and threat. _____
Title: Impaired Fear Memories Are Correlated With Subregion-Specific Deficits in Hippocampal and Amygdalar LTP. Author(s): Schimanski, Lesley A., Department of Physiology, University of Alberta, School of Medicine, Edmonton, AB, Canada; Nguyen, Peter V., Department of Physiology, University of Alberta, School of Medicine, Edmonton, AB, Canada, peter.nguyen@ualberta.ca Address: Nguyen, Peter V., Department of Physiology, University of Alberta School of Medicine, 7-14 Medical Sciences Building, Edmonton, AB, Canada, T6G 2H7, peter.nguyen@ualberta.ca Source: Behavioral Neuroscience, Vol 119(1), Feb 2005. pp. 38-54. Publisher: US: American Psychological Assn Abstract: Inbred mouse strains have different genetic backgrounds that likely influence memory and long-term potentiation (LTP). LTP, a form of synaptic plasticity, is a candidate cellular mechanism for some forms of learning and memory. Strains with impaired fear memory may have selective LTP deficits in different hippocampal subregions or in the amygdala. The authors assessed fear memory in 4 inbred strains: C57BL/6NCrlBR (B6), 129S1/SvImJ (129), C3H/HeJ (C3H), and DBA/2J (D2). The authors also measured LTP in the hippocampal Schaeffer collateral (SC) and medial perforant pathways (MPP) and in the basolateral amygdala. Contextual and cued fear memory, and SC and amygdalar LTP, were intact in B6 and 129, but all were impaired in C3H and D2. MPP LTP was similar in all 4 strains. Thus, SC, but not MPP, LTP correlates with hippocampus-dependent contextual memory expression, and amygdalar LTP correlates with amygdala-dependent cued memory expression, in these inbred strains. _____
Title: Perception of facial expressions and voices and of their combination in the human brain. Author(s): Pourtois, Gilles, Donders Laboratory for Cognitive and Affective Neuroscience, University of Tilburg, Tilburg, Netherlands, gilles.pourtois@medecine.unige.ch; de Gelder, Beatrice, Donders Laboratory for Cognitive and Affective Neuroscience, University of Tilburg, Tilburg, Netherlands; Bol, Anne, Positron Emission Tomography Laboratory, University of Louvain, Louvain-La-Neuve, Belgium; Crommelinck, Marc, Laboratory of Neurophysiology, University of Louvain, Brussels, Belgium Address: Pourtois, Gilles, Neurology and Imaging of Cognition, University Medical Center (CMU), Bat. A, Physiology, 7th floor, room 7042, 1 rue Michel-Servet, CH-1211, Geneva, Switzerland, gilles.pourtois@medecine.unige.ch Source: Cortex, Vol 41(1), Feb 2005. pp. 49-59. Publisher: Italy: Masson Italia Abstract: Using positron emission tomography we explored brain regions activated during the perception of face expressions, emotional voices and combined audio-visual pairs. A convergence region situated in the left lateral temporal cortex was more activated by bimodal stimuli than by either visual only or auditory only stimuli. Separate analyses for the emotions happiness and fear revealed supplementary convergence areas situated mainly anteriorly in the left hemisphere for happy pairings and in the right hemisphere for fear pairings indicating different neuro-anatomical substrates for multisensory integration of positive versus negative emotions. Activation in the right extended amygdala was obtained for fearful faces and fearful audio-visual pairs but not for fearful voices only. These results suggest that during the multisensory perception of emotion, affective information from face and voice converge in heteromodal regions of the human brain. _____
Title: The Neuroscience of Mammalian Associative Learning. Author(s): Fanselow, Michael S., Department of Psychology, University of California, Los Angeles, CA, US, fanselow@ucla.edu; Poulos, Andrew M., Neuroscience Program, University of Southern California, Los Angeles, CA, US, apoulos@neuro.usc.edu Address: Fanselow, Michael S., Department of Psychology, University of California, Los Angeles, CA, US, fanselow@ucla.edu Source: Annual Review of Psychology, Vol 56, 2005. pp. 207-234. Publisher: US: Annual Reviews Abstract: Mammalian associative learning is organized into separate anatomically defined functional systems. We illustrate the organization of two of these systems, Pavlovian fear conditioning and Pavlovian eyeblink conditioning, by describing studies using mutant mice, brain stimulation and recording, brain lesions and direct pharmacological manipulations of specific brain regions. The amygdala serves as the neuroanatomical hub of the former, whereas the cerebellum is the hub of the latter. Pathways that carry information about signals for biologically important events arrive at these hubs by circuitry that depends on stimulus modality and complexity. Within the amygdala and cerebellum, neural plasticity occurs because of convergence of these stimuli and the biologically important information they predict. This neural plasticity is the physical basis of associative memory formation, and although the intracellular mechanisms of plasticity within these structures share some similarities, they differ significantly. The last Annual Review of Psychology article to specifically tackle the question of mammalian associative learning (Lavond et al. 1993) persuasively argued that identifiable "essential" circuits encode memories formed during associative learning. The next dozen years saw breathtaking progress not only in detailing those essential circuits but also in identifying the essential processes occurring at the synapses (e.g., Bi & Poo 2001, Martinez & Derrick 1996) and within the neurons (e.g., Malinow & Malenka 2002, Murthy & De Camilli 2003) that make up those circuits. In this chapter, we describe the orientation that the neuroscience of learning has taken and review some of the progress made within that orientation. _____
Title: Have no fear, erythropoietin is here: Erythropoietin protects fear conditioning performances after functional inactivation of the amygdala. Author(s): Miu, Andrei C., Laboratory of Cognitive Neuroscience, Department of Psychology, Babes-Bolyai University, Cluj-Napoca, Romania, andreimiu@psychology.ro; Olteanu, Adrian I., Laboratory of Cognitive Neuroscience, Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Chis, Irina, Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, I Clinicilor, Cluj-Napoca, Romania; Heilman, Renata M., Neuroscience Research Nucleus, Department of Psychology, Babes-Bolyai University, Cluj-Napoca, Romania Address: Miu, Andrei C., Laboratory of Cognitive Neuroscience, Department of Psychology, Babes-Bolyai University, 37 Republicii, Cluj-Napoca, Romania, CJ 3400, andreimiu@hotmail.com Source: Behavioural Brain Research, Vol 155(2), Dec 2004. pp. 223-229. Publisher: Netherlands: Elsevier Science Abstract: This study investigated the capacity of erythropoietin (EPO) to protect fear conditioning performances against functional inactivation of the amygdala. We infused an excitotoxic dose of glutamate in the lateral nucleus of the amygdala (LA) of adult rats in order to block the output projections to brainstem areas controlling the expression of conditioned fear responses. Subsequently, animals with excitotoxic lesions in the LA displayed altered short and long-term fear conditioned responses, but the integrity of their general emotional reactivity was preserved, as indicated by their open-field behavior. EPO infused immediately after glutamate succeeded to protect the conditioned fear performances of rats. This effect was reliably represented on both short, and long-term memory tests of conditioned fear. This and other studies have supported the potent neuroprotective activity of EPO, discriminable both morphologically, and behaviorally. _____
Title: Omega-3 Status and Cerebrospinal Fluid Corticotrophin Releasing Hormone in Perpetrators of Domestic Violence. Author(s): Hibbeln, Joseph R., National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, US, jhibbeln@mail.nih.gov; Bissette, Garth, University of Mississippi Medical Center, Jackson, MS, US; Umhau, John C., National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, US; George, David T., National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, US Address: Hibbeln, Joseph R., Laboratory of Membrane Biophysics and Biochemistry, NIAAA, DICBR, 12420 Parklawn Drive, Room 1-14, Rockville, MD, US, jhibbeln@mail.nih.gov Source: Biological Psychiatry, Vol 56(11), Dec 2004. pp. 895-897. Publisher: Netherlands: Elsevier Science Abstract: Background: Elevated levels of corticotrophin-releasing hormone in the cortical-hippocampal-amygdala pathway increase fear and anxiety, which are components of defensive and violent behaviors. Prostaglandins E-sub-2 and F-sub(2α), which increase corticotrophin-releasing hormone RNA expression in this pathway, are reduced by dietary intakes of omega-3 fats. Methods: Among 21 perpetrators of domestic violence, cerebrospinal fluid and plasma were assessed for corticotrophin-releasing hormone and fatty acid compositions, respectively. Results: Lower plasma docosahexaenoic acid (wt% fatty acids) alone predicted greater cerebrospinal fluid corticotrophin-releasing hormone (pg/mL), in exponential (r = -.67, p < .006) and linear regressions (r = -0.68, p < .003 excluding four subjects with the highest docosahexaenate levels). Conclusions: In this small observational study, low plasma docosahexaenoic acid levels were correlated to higher cerebrospinal fluid corticotrophin-releasing hormone levels. Placebo controlled trials can determine if dietary omega-3 fatty acids can reduce excessive corticotrophin-releasing hormone levels in psychiatric illnesses. _____
Title: Perception of Emotion on Faces in Frontotemporal Dementia and Alzheimer's Disease: A Longitudinal Study. Author(s): Lavenu, I., Memory Disorders Unit, Department of Neurology, University Hospital of Lille, Lille, France; Pasquier, Florence, Memory Disorders Unit, Department of Neurology, University Hospital of Lille, Lille, France, pasquier@chru-lille.fr Address: Lavenu, I., Department of Neurology, University Hospital CHRU, FR-59037, Lille, France Source: Dementia & Geriatric Cognitive Disorders, Vol 19(1), Dec 2004. pp. 37-41. Publisher: Switzerland: Karger Abstract: Frontotemporal dementia (FTD) is a neurodegenerative disease characterised by behavioural disorders that suggest abnormalities of emotional processing. In a previous study, we showed that patients with Alzheimer's disease (AD) and with FTD were equally able to distinguish a face displaying affect from one not displaying affect. However, recognition of emotion was worse in patients with FTD than in patients with AD who did not differ significantly from controls. The aim of this study was to follow up the perception of emotions on faces in these patients. The poor perception of emotion could worsen differently in AD and in FTD, with the progression of atrophy of the amygdala, the anterior temporal cortex and the orbital frontal cortex, structures that are components of the brain's emotional processing systems. Methods: Patients with AD or with FTD had to recognise and point out the name of one of seven basic emotions (anger, disgust, happiness, fear, sadness, surprise and contempt) on a set of 28 faces presented on slides at the first visit and 3 years later. Results: Thirty-seven patients (AD = 19, FTD = 18) performed the tests initially. The two patient groups did not differ for age, sex and duration of the disease. During the follow-up, 12 patients died, 4 patients refused to perform the tests and 8 could not be tested because of the severity of the disease. Finally, 7 patients with AD and 6 patients with FTD performed the two tests at a mean delay of 40 months. All patients with AD had worse results at follow-up on the perception of emotion despite the prescription of inhibitors of cholinesterase in all patients and of selective serotonin reuptake inhibitors (SSRIs) in 4 patients. As a whole, patients with FTD had better results in the second than in the first assessment (however, 3 of them had worse results) independently of the prescription of trazodone (n = 2), other SSRIs (n = 2), or the absence of treatment (n = 2), and of possible cognitive change. Conclusions: Recognition of emotion on faces in AD decreases with the progression of dementia and could be related to the progression of the degeneration of the structures implicated in emotional processing systems. Inconsistency of the results in FTD may be related to impulsiveness, lack of consistency of the patients and to heterogeneity of the progression of the lesions. _____
Title: Fear and the Amygdala: Manipulation of Awareness Generates Differential Cerebral Responses to Phobic and Fear-Relevant (but Nonfeared) Stimuli. Author(s): Carlsson, Katrina, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Petersson, Karl Magnus, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Lundqvist, Daniel, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Karlsson, Andreas, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Ingvar, Martin, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Öhman, Arne, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, arne.ohman@cns.ki.se Address: Öhman, Arne, Department of Clinical Neuroscience, Karolinska Institute & Hospital, SE-171 76, Stockholm, Sweden, arne.ohman@cns.ki.se Source: Emotion, Vol 4(4), Dec 2004. pp. 340-353. Publisher: US: American Psychological Assn Abstract: Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing. _____
Title: Molecular mechanisms of neuroplasticity and pharmacological implications: The example of tianeptine. Author(s): McEwen, Bruce S., Harold and Margaret Milliken Hatch-Laboratory of Nenroendocrinology, Rockefeller University, New York, NY, US, mcewen@mail.rockefeller.edu; Chattarji, Sumantra, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India Address: McEwen, Bruce S., Harold and Margaret Milliken Hatch-Laboratory of Nenroendocrinology, Rockefeller University, New York, NY, US, mcewen@mail.rockefeller.edu Source: European Neuropsychopharmacology, Vol 14(Suppl5), Dec 2004. pp. S497-S502. Publisher: Netherlands: Elsevier Science Abstract: The hippocampal formation, which expresses high levels of adrenal steroid receptors, is a malleable brain structure that is important for certain types of learning and memory. This structure is also vulnerable to the effects of stress hormones which have been reported to be increased in depressed patients, particularly those with severe depression. The amygdala, a structure that plays a critical role in fear learning, is also an important target of anxiety and stress. Certain animal models of depression involve application of repeated stress. Repeated stress promotes behavioral changes that can be associated with these two brain structures such as impairment of hippocampus-dependent memory and enhancement of fear and aggression, which are likely to reflect amygdala function. At a cellular level, opposite responses in the hippocampus and amygdala are observed, namely, shrinkage of dendrites in hippocampus and growth of dendrites in the lateral amygdala, involving in both cases a remodeling of dendrites. Furthermore, stress-induced suppression of neurogenesis has been noted in dentate gyrus. At a molecular level, the effects of repeated stress in the hippocampus involve excitatory amino acids and the induction of the glial form of the glutamate transporter. Chronic treatment with the antidepressant tianeptine may prevent these effects in hippocampus and amygdala. _____
Title: Neurophysiological correlates of habituation during exposure in spider phobia. Author(s): Veltman, Dick J., Department of Psychiatry and Clinical PET Center, Vrije Universiteit Medical Center, Amsterdam, Netherlands, dj.veltman@vumc.nl; Tuinebreijer, Wim E., Department of Clinical Psychology, University of Amsterdam, Amsterdam, Netherlands; Winkelman, Daniël, Clinical PET Center, Vrije Universiteit Medical Center, Amsterdam, Netherlands; Lammertsma, Adriaan A., Clinical PET Center, Vrije Universiteit Medical Center, Amsterdam, Netherlands; Witter, Menno P., Department of Anatomy, Vrije Universiteit Medical Center, Amsterdam, Netherlands; Dolan, Raymond J., Wellcome Department of Cognitive Neurology, Institute of Neurology, London, United Kingdom; Emmelkamp, Paul M. G., Department of Clinical Psychology, University of Amsterdam, Amsterdam, Netherlands Address: Veltman, Dick J., Department of Psychiatry and Clinical PET Center, Vrije Universiteit Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB, Amsterdam, Netherlands, dj.veltman@vumc.nl Source: Psychiatry Research: Neuroimaging, Vol 132(2), Dec 2004. pp. 149-158. Publisher: Netherlands: Elsevier Science Abstract: Imaging studies using symptom-provocation paradigms in specific phobia have yielded contradictory results, possibly reflecting a failure to account for habituation processes. Given that a single session of exposure in vivo can result in significant improvement in specific phobia, we used prolonged exposure to phobic stimuli to identify CNS regions showing habituation. Eighteen subjects (12 with spider phobia, 6 healthy controls) underwent H-sub-2¹-sup-5O-positron emission tomography while being continuously presented with pictures of spiders or butterflies. Results showed main effects (spiders>butterflies) in the phobia group in the left fusiform gyrus (FG) and the right parahippocampal gyrus (PHG), with bilateral perirhinal cortex and right limbic areas approaching significance. Group x condition effects were found in the right amygdala and PHG. During spider scans, large habituation effects were observed in the anterior medial temporal lobe (MTL) bilaterally. Regression analyses demonstrated that state anxiety was correlated with activity in left amygdala, bilateral perirhinal cortex, right FG, and periaquaductal grey; by contrast, phobic fear was only associated with right-sided hippocampal activity. We conclude that prolonged exposure to phobic stimuli is associated with a significant decrease in bilateral anterior MTL regional cerebral blood flow. Right anterior MTL, identified when comparing phobic vs. neutral stimuli and habituation to phobic vs. neutral stimuli in the phobia group, implicates this region in phobic fear. Analyses of covariance suggest a further functional segregation with state anxiety being linked to enhanced activity in amygdala, perirhinal cortex, and tegmentum, and phobic fear with enhanced right hippocampal activity, suggesting a neuroanatomical differentiation between emotional-vegetative and cognitive aspects of (phobic) fear. _____
Title: Human Amygdala Responsivity to Masked Fearful Eye Whites. Author(s): Whalen, Paul J., Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US, pwhalen@wisc.edu; Kagan, Jerome, Department of Psychology, Harvard University, Cambridge, MA, US; Cook, Robert G., Department of Psychology, Tufts University, Medford, MA, US; Davis, F. Caroline, Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; Kim, Hackjin, Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; Polis, Sara, Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; McLaren, Donald C., Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; Somerville, Leah H., Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, US; McLean, Ashly A., Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; Maxwell, Jeffrey S., Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US; Johnstone, Tom, Department of Psychiatry, W. M. Keck Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, US Address: Whalen, Paul J., pwhalen@wisc.edu Source: Science, Vol 306(5704), Dec 2004. pp. 2061. Publisher: US: American Assn for the Advancement of Science Abstract: The human amygdala has been shown to be activated robustly by fearful facial expressions in neuroimaging studies, even when expressions are presented with backward masking techniques that decrease the temporal availability of facial expression information and mitigate subjective awareness of their presence. This efficiency in information processing could be consistent with the proposal that the amygdala can respond to crude representations of stimuli. On the basis of data showing that the eye region of the face is one of the key regions where expression information is extracted and data showing that the amygdala is responsive to the "wide-eyed" expressions of both fear and surprise, we hypothesized that the larger size of fearful eye whites (i.e., sclera) would be sufficient to modulate amygdala responsivity. To test this possibility, we modified standardized fearful and happy face stimuli by removing all information from the face but the eye whites. Because presentation of eye whites alone represents a noncanonical stimulus, we presented these stimuli in a backward masking paradigm to decrease subject's awareness of their presence and, in turn, of their aberrant nature. During functional magnetic resonance imaging, 20 subjects viewed neutral face mask presentations, half of which were preceded by fearful eye whites (larger) and half of which were preceded by happy eye whites (smaller). Signal intensity within the ventral amygdala was greater to fearful than to happy eye whites. _____
Title: Differential regulation of brain-derived neurotrophic factor transcripts during the consolidation of fear learning. Author(s): Rattiner, Lisa M., Emory University School of Medicine, Center for Behavioral Neurosdence, Yerkes Research Center, Atlanta, GA, US; Davis, Michael, Emory University School of Medicine, Center for Behavioral Neurosdence, Yerkes Research Center, Atlanta, GA, US; Ressler, Kerry J., Emory University School of Medicine, Center for Behavioral Neurosdence, Yerkes Research Center, Atlanta, GA, US, kressle@emory.edu Address: Ressler, Kerry J., Emory University School of Medicine, Center for Behavioral Neuroscience, Yerkes Research Center, Atlanta, GA, US, kressle@emory.edu Source: Learning & Memory, Vol 11(6), Nov-Dec 2004. pp. 727-731. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: Brain-derived neurotrophic factor (BDNF) has been implicated as a molecular mediator of learning and memory. The BDNF gene contains four differentially regulated promoters that generate four distinct mRNA transcripts, each containing a unique noncoding 5'-exon and a common 3'-coding exon. This study describes novel evidence for the differential usage of alternative BDNF promoters and 5'-exons during the consolidation of learning. We found a selective increase in BDNF transcripts containing exons I and III in the amygdala 2 h following fear conditioning, while mRNA levels of BDNF exons II and IV remained unchanged. These results provide the first evidence of differential splicing and/or differential BDNF promoter usage in response to a behaviorally relevant learning paradigm. _____
Title: Olfactory fear conditioning induces field potential potentiation in rat olfactory cortex and amygdala. Author(s): Sevelinges, Yannick, Institut des Sciences Cognitives, Unité Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Université Lyon 1, Institut Federatif des Neurosciences, Bron, France; Gervais, Rémi, Institut des Sciences Cognitives, Unité Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Université Lyon 1, Institut Federatif des Neurosciences, Bron, France; Messaoudi, Belkacem, Institut des Sciences Cognitives, Unité Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Université Lyon 1, Institut Federatif des Neurosciences, Bron, France; Granjon, Lionel, Institut des Sciences Cognitives, Unité Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Université Lyon 1, Institut Federatif des Neurosciences, Bron, France; Mouly, Anne-Marie, Institut des Sciences Cognitives, Unité Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Université Lyon 1, Institut Federatif des Neurosciences, Bron, France, mouly@isc.cnrs.fr Address: Mouly, Anne-Marie, Institut des Sciences Cognitives, Unite Mixte de Recherche (UMR) 5015, Centre National de la Recherche Scientifique, Universite Lyon 1, Institut Federatif des Neurosciences, (IFR 19), 69675, Bron, France, Cedex, mouly@isc.cnrs.fr Source: Learning & Memory, Vol 11(6), Nov-Dec 2004. pp. 761-769. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of plasticity in the olfactory pathway. Training consisted of a single training session including six pairings of an odor CS with a mild foot-shock unconditioned stimulus (US). Twenty-four hours later, the animals were tested for retention of the CS as assessed by the amount of freezing exhibited in the presence of the learned odor. Behavioral data showed that trained animals exhibited a significantly higher level of freezing in response to the CS than control animals. In the same animals, EFPs were recorded in parallel in the anterior piriform cortex (aPC), posterior piriform cortex (pPC), cortical nucleus of the amygdala (CoA), and basolateral nucleus of the amygdala (BLA) following electrical stimulation of the olfactory bulb. Specifically, EFPs recorded before (baseline) and after (during the retention test) training revealed that trained animals exhibited a lasting increase (present before and during presentation of the CS) in EFP amplitude in CoA, which is the first amygdaloid target of olfactory information. In addition, a transient increase was observed in pPC and BLA during presentation of the CS. These data indicate that the olfactory and auditory fear-conditioning neural networks have both similarities and differences, and suggest that the fear-related behaviors in each sensory system may have at least some distinct characteristics. _____
Title: An egr-1 (zif268) antisense oligodeoxynucleotide infused into the amygdala disrupts fear conditioning: Errata. Author(s): Malkani, Seema, Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Wallace, Karin J., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Donley, Melanie P., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Rosen, Jeffrey B., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US, jrosen@udel.edu Address: Rosen, Jeffrey B., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US, jrosen@udel.edu Source: Learning & Memory, Vol 11(6), Nov-Dec 2004. pp. 797. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: Reports an error in the original article by Malkani et al (Learning & Memory, 2004[Sep-Oct], Vol 11[5], 617-624). This article was mistakenly included in the Special Issue. It should have appeared in the November/December 2004 issue of Learning & Memory. (The following abstract of this article originally appeared in record 2004-19377-020.) Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, egr-1, is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that egr-1 and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To directly test this hypothesis, an egr-1 antisense Oligodeoxynucleotide (antisense-ODN) was injected bilaterally into the amygdala prior to contextual fear conditioning. The antisense-ODN reduced Egr-1 protein in the amygdala and interfered with fear conditioning. A 250-pmole dose produced an 11% decrease in Egr-1 protein and reduced long-term memory of fear as measured by freezing in a retention test 24 h after conditioning, but left shock-induced freezing intact. A larger 500-pmole dose produced a 25% reduction in Egr-1 protein and significantly decreased both freezing immediately following conditioning and freezing in the retention test. A nonsense-ODN had no effect on postshock or retention test freezing. In addition, 500 pmole of antisense-ODN infused prior to the retention test in previously trained rats did not reduce freezing, indicating that antisense-ODN did not suppress conditioned fear behavior. Finally, rats infused with 500 pmole of antisense-ODN displayed unconditioned fear to a predator odor, demonstrating that unconditioned freezing was unaffected by the antisense-ODN. The data indicate that the egr-1 antisense-ODN interferes with learning and memory processes of fear without affecting freezing behavior and suggests that the inducible transcription factor Egr-1 within the amygdala plays important functions in long-term learning and memory of fear. _____
Title: Neuronal signalling of fear memory. Author(s): Maren, Stephen, Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, MI, US, maren@umich.edu; Quirk, Gregory J., Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico, gjquirk@yahoo.com Address: Maren, Stephen, Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, MI, US, maren@umich.edu Source: Nature Reviews Neuroscience, Vol 5(11), Nov 2004. pp. 844-852. Publisher: United Kingdom: Nature Publishing Group Abstract: The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour. _____
Title: Understanding contextual fear conditioning: Insights from a two-process model. Author(s): Rudy, J. W., Department of Psychology, University of Colorado, Boulder, CO, US, rudy@psych.colorado.edu; Huff, N. C., Department of Psychology, University of Colorado, Boulder, CO, US; Matus-Amat, P., Department of Psychology, University of Colorado, Boulder, CO, US Address: Rudy, J. W., Department of Psychology, University of Colorado, Boulder, CO, US, rudy@psych.colorado.edu Source: Neuroscience & Biobehavioral Reviews, Vol 28(7), Nov 2004. Special issue: Neurobiology of Cognition in Laboratory Animals: Challenges and Opportunities. pp. 675-685. Publisher: Netherlands: Elsevier Science Abstract: Contextual fear conditioning is an important behavioral paradigm for studying the neurobiology of learning and memory and the mnemonic function of the hippocampus. We suggest that research in this domain can profit by a better theoretical understanding of the processes that contribute to this phenomenon. To facilitate this understanding, we describe a theory which assumes that physical elements of a conditioning context represented in the brain as either (a) a set of independent features or (b) features bound into a conjunctive representation by the hippocampus which supports pattern completion. Conditioning produced by shocking a rat in a particular context, in principle, can be produced by strengthening connections between the feature representations and/or the conjunctive representation and basolateral region of the amygdala. We illustrate how this theory clarifies some of the complexities associated with the existing literature and how it can be used to guide future empirical work. We also argue that the mechanisms (conjunctive representations and pattern completion) that mediate the contribution the hippocampus makes to contextual fear conditioning are the same ones that enable the hippocampus to support declarative memory in humans. _____
Title: Pretraining Inactivation of the Caudal Pontine Reticular Nucleus Impairs the Acquisition of Conditioned Fear-Potentiated Startle to an Odor, but Not a Light. Author(s): Weber, Marianne, University of New South Wales, Sydney, NSW, Australia; Richardson, Rick, University of New South Wales, Sydney, NSW, Australia, R.Richardson@unsw.edu.au Address: Richardson, Rick, School of Psychology, University of New South Wales, Sydney, NSW, Australia, 2052, R.Richardson@unsw.edu.au Source: Behavioral Neuroscience, Vol 118(5), Oct 2004. pp. 965-974. Publisher: US: American Psychological Assn Abstract: Recent data from developing rats suggest that structures downstream from the amygdala are involved in the acquisition of conditioned fear-potentiated startle (FPS). The authors tested this idea in adult rats by temporarily inactivating the structure critical for FPS, the caudal pontine reticular nucleus (PnC), during fear conditioning. When the conditioned stimulus (CS) was an odor, rats displayed freezing, but not FPS, at test. This effect was not due to a decrease in footshock sensitivity. Further, no savings were evident on retraining. When the CS was a light, inactivation of the PnC had no effect on the acquisition of FPS. Thus, the PnC may be crucial for the acquisition of conditioned FPS to an odor, but not a light. _____
Title: Environmental Enrichment Facilitates Amygdala Kindling but Reduces Kindling-Induced Fear in Male Rats. Author(s): Young, Nicole A., Dalhousie University, Halifax, NS, Canada; Wintink, Amanda J., Dalhousie University, Halifax, NS, Canada; Kalynchuk, Lisa E., Dalhousie University, Halifax, NS, Canada, lisa.kalynchuk@dal.ca Address: Kalynchuk, Lisa E., Department of Psychology, Dalhousie University, 1355 Oxford Street, Halifax, NS, Canada, B3H 4J1, lisa.kalynchuk@dal.ca Source: Behavioral Neuroscience, Vol 118(5), Oct 2004. pp. 1128-1133. Publisher: US: American Psychological Assn Abstract: The purpose of this experiment was to determine the effect of prior environmental enrichment on the acquisition of kindling and the expression of kindling-induced fear. Sixty male rats were housed either in an enriched environment or in isolation, starting immediately after weaning. As adults, they were subjected to either 50 amygdala-kindling stimulations or sham stimulations, followed by testing in an unfamiliar open field. The kindled-enriched rats acquired the kindled state more quickly than did the kindled-isolated rats, but they also showed less fear in the open field than did the kindled-isolated rats. These results suggest that environmental enrichment has differential effects on kindling acquisition and its behavioral consequences. _____
Title: The Development of Social Behavior Following Neonatal Amygdala Lesions in Rhesus Monkeys. Author(s): Bauman, M. D., University of California, Davis, CA, US; Lavenex, P., University of California, Davis, CA, US; Mason, W. A., University of California, Davis, CA, US; Capitanio, J. P., University of California, Davis, CA, US; Amaral, D. G., University of California, Davis, CA, US, dgamaral@ucdavis.edu Address: Amaral, D. G., M.I.N.D. Institute, University of California-Davis, 2825 50th Street, Sacramento, CA, US, dgamaral@ucdavis.edu Source: Journal of Cognitive Neuroscience, Vol 16(8), Oct 2004. Special issue: Special Issue on Developmental Cognitive Neuroscience. pp. 1388-1411. Publisher: US: MIT Press Abstract: We examined the role of the amygdala in the development of nonhuman primate social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid lesions of either the amygdala or the hippocampus or received a sham surgical procedure at 2 weeks of age. Subjects were reared with their mothers and were provided daily access to social rearing cohorts. The subjects were weaned at 6 months of age and then observed while paired with familiar conspeciflcs at 6 and 9 months of age and with unfamiliar conspecifics at 1 year of age. The subjects were also observed during daily cohort socialization periods. Neither amygdala nor hippocampus lesions altered fundamental aspects of social behavior development. All subjects, regardless of lesion condition, developed a species-typical repertoire of social behavior and displayed interest in conspeciflcs during social encounters. The amygdala lesions, however, clearly affected behaviors related to fear processing. The amygdala-lesioned subjects produced more fear behaviors during social encounters than did control or hippocampus-lesioned subjects. Although the heightened fear response of the amygdala-lesioned subjects was consistent across different testing paradigms and was observed with both familiar and novel partners, it did not preclude social interactions. In fact, the amygdala-lesioned subjects displayed particular social behaviors, such as following, cooing, grunting, presenting to be groomed, and presenting to be mounted more frequently than either control or hippocampus-lesioned subjects. These findings are consistent with the view that the amygdala is not needed to develop fundamental aspects of social behavior and may be more related to the detection and avoidance of environmental dangers. _____
Title: Increased fear learning coincides with neuronal dysinhibition and facilitated LTP in the basolateral amygdala following benzodiazepine withdrawal in rats. Author(s): Isoardi, Nora A., Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina; Martijena, Irene D., Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina; Carrer, Hugo F., Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Córdoba, Argentina; Molina, Víctor A., Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina, vmolina@fcq.unc.edu.ar Address: Molina, Víctor A., Departamento de Farmacologia, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Ciudad Universitaria, Haya de la Torre esq. Medina Allende, 5016, Cordoba, Argentina, vmolina@fcq.unc.edu.ar Source: Neuropsychopharmacology, Vol 29(10), Oct 2004. pp. 1852-1864. Publisher: United Kingdom: Nature Publishing Abstract: Animals chronically administered with diazepam (DZM--2 mg/kg/day i.p.) or vehicle (VEH) for 21 days were tested in a fear-conditioning paradigm 4 days after the last administration. Increased freezing was observed in DZM withdrawn rats as compared to VEH injected control rats in both associative and nonassociative context and this increase was greatest for the DZM withdrawal group in the paired context. In animals anesthetized with urethane, single pulses in the medial prefrontal cortex evoked a field potential including a population spike (PS) in the basolateral complex of the amygdala (BLA) of control animals, whereas in DZM withdrawn animals multiple PSs were evoked. In brain slices from control rats, stimulation of the external capsule evoked a field potential including a PS in the BLA, whereas in DZM withdrawn rats multiple PSs were evoked. The amplitude of the PS was smaller in slices obtained from DZM withdrawn rats than from control rats, and paired pulse inhibition was significantly less in the former. Perfusion with DZM 2 μM of slices obtained from DZM withdrawn rats eliminated repetitive spiking. GABAergic blockade with 50 μM picrotoxin in control rats resulted in the appearance of multiple secondary PSs. In slices from DZM withdrawn rats high-frequency stimulation induced a highly significant potentiation that lasted at least 2h (LTP), whereas in control rats the same stimulation did not induce LTP. Neuronal hyperexcitability leading to facilitated LTP observed in BLA of DZM withdrawn rats could be due to depressed GABAergic activity (dysinhibition). The increased synaptic plasticity may be at the root of the increased fear learning observed in withdrawn animals. _____
Title: Reduced sensitivity to others' fearful expressions in psychopathic individuals. Author(s): Blair, R. J. R., Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institute of Health, Bethesda, MD, US, blairj@intra.nimh.nih.gov; Mitchell, D. G. V., Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institute of Health, Bethesda, MD, US; Peschardt, K. S., Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institute of Health, Bethesda, MD, US; Colledge, E., SGDP Research Center, Institute of Psychiatry, King's College, United Kingdom; Leonard, R. A., HMP Wormwood Scrubs, United Kingdom; Shine, J. H., Department of Psychology, HMP Grendon and Springhill, United Kingdom; Murray, L. K., School of Psychology, University of St. Andrews, St. Andrews, United Kingdom; Perrett, D. I., School of Psychology, University of St. Andrews, St. Andrews, United Kingdom Address: Blair, R. J. R., Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institute of Health, 15K North Drive, Room 206, MSC 2760, Bethesda, MD, US, blairj@intra.nimh.nih.gov Source: Personality & Individual Differences, Vol 37(6), Oct 2004. pp. 1111-1122. Publisher: Netherlands: Elsevier Science Abstract: This study investigates the ability of psychopathic individuals to process facial emotional expressions. Psychopathic and comparison individuals, as denned by the Hare Psychopathy Checklist Revised (PCL-R), were presented with a standardized set of facial expressions depicting six emotions: happy, surprised, disgusted, angry, sad and fearful. Participants observed as these facial expressions slowly evolved through 20 successive frames of increasing intensity. The dependent variables were latency in responding as measured by frame and number of errors. The psychopathic individuals showed selective impairment for the recognition of fearful expressions. The results are interpreted with reference to the Violence Inhibition Mechanism model of psychopathy and the suggestion that psychopathic individuals present with amygdala dysfunction. _____
Title: The dynamics of cortico-amygdala and autonomic activity over the experimental time course of fear perception. Author(s): Williams, Leanne M., Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia, lea@psych.usyd.edu.au; Brown, Kerri J., Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia; Das, Pritha, Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia; Boucsein, Wolfram, Department of Physiological Psychology, University of Wuppertal, Wuppertal, Germany; Sokolov, Evgeni N., Department of Psychophysiology, Moscow State University, Moscow, Russia; Brammer, Michael J., Department of Biostatistics and Computing, Institute of Psychiatry, London, United Kingdom; Olivieri, Gloria, Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia; Peduto, Anthony, Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia; Gordon, Evian, Brain Dynamics Centre, Westmead Hospital, Westmead, NSW, Australia Address: Williams, Leanne M., Brain Dynamics Centre, Westmead Hospital, Acacia House, Westmead, NSW, Australia, lea@psych.usyd.edu.au Source: Cognitive Brain Research, Vol 21(1), Sep 2004. pp. 114-123. Publisher: Netherlands: Elsevier Science Abstract: Human neuroimaging studies implicate the amygdala, medial prefrontal and somatosensory-related cortices as key neural components in the perception of facial fear signals. Yet, their temporal sequence and interaction with autonomic arousal is not known. We used simultaneous functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording in 22 healthy subjects to examine central and autonomic responses to repeated fearful expressions. Phasic SCRs followed a U-shape pattern across early, middle and late presentations of fear stimuli. fMRI data revealed a concomitant temporal sequence of preferential somatosensory insula, dorsomedial prefrontal cortex and left amygdala engagement. These findings suggest that sustained cortico-amygdala and autonomic responses may serve to prime the emotional content of fear signals, and differentiate them from initial stimulus novelty. _____
Title: Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Author(s): Knight, David C., University of Wisconsin, Milwaukee, WI, US; Smith, Christine N., University of Wisconsin, Milwaukee, WI, US; Cheng, Dominic T., University of Wisconsin, Milwaukee, WI, US; Stein, Elliot A., Medical College of Wisconsin, Milwaukee, WI, US; Helmstetter, Fred J., University of Wisconsin, Milwaukee, WI, US, fjh@uwm.edu Address: Helmstetter, Fred J., Department of Psychology, University of Wisconsin, P.O. Box 413, Milwaukee, WI, US, fjh@uwm.edu Source: Cognitive, Affective & Behavioral Neuroscience, Vol 4(3), Sep 2004. pp. 317-325. Publisher: US: Psychonomic Society Abstract: Previous functional magnetic resonance imaging (fMRI) studies have characterized brain systems involved in conditional response acquisition during Pavlovian fear conditioning. However, the functional neuroanatomy underlying the extinction of human conditional fear remains largely undetermined. The present study used fMRI to examine brain activity during acquisition and extinction of fear conditioning. During the acquisition phase, participants were either exposed to light (CS) presentations that signaled a brief electrical stimulation (paired group) or received light presentations that did not serve as a warning signal (control group). During the extinction phase, half of the paired group subjects continued to receive the same treatment, whereas the remainder received light alone. Control subjects also received light alone during the extinction phase. Changes in metabolic activity within the amygdala and hippocampus support the involvement of these regions in each of the procedural phases of fear conditioning. Hippocampal activity developed during acquisition of the fear response. Amygdala activity increased whenever experimental contingencies were altered, suggesting that this region is involved in processing changes in environmental relationships. The present data show learning-related amygdala and hippocampal activity during human Pavlovian fear conditioning and suggest that the amygdala is particularly important for forming new associations as relationships between stimuli change. _____
Title: Patterns of neural activation associated with exposure to odors from a familiar winner in male golden hamsters. Author(s): Lai, Wen-Sung, Department of Psychology, Cornell University, Ithaca, NY, US, wl2120@columbia.edu; Chen, Aiyin, Department of Psychology, Cornell University, Ithaca, NY, US; Johnston, Robert E., Department of Psychology, Cornell University, Ithaca, NY, US, rej1@cornell.edu Address: Johnston, Robert E., Department of Psychology, Cornell University, 286 Uris Hall, Ithaca, NY, US, rej1@cornell.edu Source: Hormones & Behavior, Vol 46(3), Sep 2004. Special issue: Olfaction, Sex, and Behavior. pp. 319-329. Publisher: Netherlands: Elsevier Science Abstract: The neural mechanisms underlying recognition of familiar individuals and responses appropriate to them are not well known. Previous studies with male golden hamsters have shown that, after a series of brief aggressive encounters, a loser selectively avoids his own, familiar winner but does not avoid other males. Using this paradigm, we investigated activity in 20 areas of the brain using immunohistochemistry for c-Fos and Egr-1 during exposure to a familiar winner compared to control groups not exposed to another male. Behavioral data showed that 1 day after fights males that lost avoided the familiar winner, suggesting that they recognized this individual. The c-Fos and Egr-1 immunohistochemistry showed that the losers exposed to familiar winners had a greater density of stained cells in the basolateral amygdala, the CA1 region of anterior dorsal hippocampus and the dorsal subiculum than control groups had in these areas. These results suggest that these brain areas may be involved in the memory for other males, the learned fear of familiar winners, or related processes. _____
Title: Context-dependent deactivation of the amygdala during pain. Author(s): Petrovic, Predrag, Karolinska Institute/Karolinska Hospital, Stockholm, Sweden; Carlsson, Katrina, Karolinska Institute/Karolinska Hospital, Stockholm, Sweden; Petersson, Karl Magnus, Karolinska Institute/Karolinska Hospital, Stockholm, Sweden; Hansson, Per, Karolinska Institute/Karolinska Hospital, Stockholm, Sweden; Ingvar, Martin, Karolinska Institute/Karolinska Hospital, Stockholm, Sweden, martin@ingvar.com Address: Ingvar, Martin, MR-centrum, Department of Clinical Neuroscience, Karolinska Hospital, 171 76, Stockholm, Sweden, martin@ingvar.com Source: Journal of Cognitive Neuroscience, Vol 16(7), Sep 2004. pp. 1289-1301. Publisher: US: MIT Press Abstract: The amygdala has been implicated in fundamental functions for the survival of the organism, such as fear and pain. In accord with this, several studies have shown increased amygdala activity during fear conditioning and the processing of fear-relevant material in human subjects. In contrast, functional neuroimaging studies of pain have shown a decreased amygdala activity. It has previously been proposed that the observed deactivations of the amygdala in these studies indicate a cognitive strategy to adapt to a distressful but in the experimental setting unavoidable painful event. In this positron emission tomography study, we show that a simple contextual manipulation, immediately preceding a painful stimulation, that increases the anticipated duration of the painful event leads to a decrease in amygdala activity and modulates the autonomic response during the noxious stimulation. On a behavioral level, 7 of the 10 subjects reported that they used coping strategies more intensely in this context. We suggest that the altered activity in the amygdala may be part of a mechanism to attenuate pain-related stress responses in a context that is perceived as being more aversive. The study also showed an increased activity in the rostral part of anterior cingulate cortex in the same context in which the amygdala activity decreased, further supporting the idea that this part of the cingulate cortex is involved in the modulation of emotional and pain networks. _____
Title: Emotional perseveration: An update on prefrontal-amygdala interactions in fear extinction. Author(s): Sotres-Bayon, Francisco, Center for Neural Science, New York University, New York, NY, US, fsotres@cns.nyu.edu; Bush, David E. A., Center for Neural Science, New York University, New York, NY, US; LeDoux, Joseph E., Center for Neural Science, New York University, New York, NY, US Address: Sotres-Bayon, Francisco, Center for Neural Science, New York University, New York, NY, US, fsotres@cns.nyu.edu Source: Learning & Memory, Vol 11(5), Sep-Oct 2004. pp. 525-535. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously learned fear. This process involves a gradual reduction in the capacity of a fear-conditioned stimulus to elicit fear by presenting the conditioned stimulus repeatedly on its own. Fear extinction is context-dependent and is generally considered to involve the establishment of inhibitory control of the prefrontal cortex over amygdala-based fear processes. In this paper, we review research progress on the neural basis of fear extinction with a focus on the role of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for how the medial prefrontal cortex inhibits amygdala output. In addition, we present new findings showing that lesions of the basal amygdala do not affect fear extinction. Based on this result, we propose an updated model for integrating hippocampal-based contextual information with prefrontal-amygdala circuitry. _____
Title: An egr-1 (zif268) antisense oligodeoxynucleotide infused into the amygdala disrupts fear conditioning. Author(s): Malkani, Seema, Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Wallace, Karin J., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Donley, Melanie P., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US; Rosen, Jeffrey B., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US, jrosen@udel.edu Address: Rosen, Jeffrey B., Program in Behavioral Neuroscience, Department of Psychology, University of Delaware, Newark, DE, US, jrosen@udel.edu Source: Learning & Memory, Vol 11(5), Sep-Oct 2004. pp. 617-624. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, egr-1, is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that egr-1 and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To directly test this hypothesis, an egr-1 antisense Oligodeoxynucleotide (antisense-ODN) was injected bilaterally into the amygdala prior to contextual fear conditioning. The antisense-ODN reduced Egr-1 protein in the amygdala and interfered with fear conditioning. A 250-pmole dose produced an 11% decrease in Egr-1 protein and reduced long-term memory of fear as measured by freezing in a retention test 24 h after conditioning, but left shock-induced freezing intact. A larger 500-pmole dose produced a 25% reduction in Egr-1 protein and significantly decreased both freezing immediately following conditioning and freezing in the retention test. A nonsense-ODN had no effect on postshock or retention test freezing. In addition, 500 pmole of antisense-ODN infused prior to the retention test in previously trained rats did not reduce freezing, indicating that antisense-ODN did not suppress conditioned fear behavior. Finally, rats infused with 500 pmole of antisense-ODN displayed unconditioned fear to a predator odor, demonstrating that unconditioned freezing was unaffected by the antisense-ODN. The data indicate that the egr-1 antisense-ODN interferes with learning and memory processes of fear without affecting freezing behavior and suggests that the inducible transcription factor Egr-1 within the amygdala plays important functions in long-term learning and memory of fear. _____
Title: CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Author(s): Cannich, Astrid, Group of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, Munich, Germany; Wotjak, Carsten T., Group of Neuronal Plasticity/Mouse Behavior, Max Planck Institute of Psychiatry, Munich, Germany; Kamprath, Kornelia, Group of Neuronal Plasticity/Mouse Behavior, Max Planck Institute of Psychiatry, Munich, Germany; Hermann, Heike, Group of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, Munich, Germany; Lutz, Beat, Group of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, Munich, Germany; Marsicano, Giovanni, Group of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, Munich, Germany, giovanni@mpipsykl.mpg.de Address: Marsicano, Giovanni, Group of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry, 80804, Munich, Germany, giovanni@mpipsykl.mpg.de Source: Learning & Memory, Vol 11(5), Sep-Oct 2004. pp. 625-632. Publisher: US: Cold Spring Harbor Laboratory Press Abstract: Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory. The molecular mechanisms underlying this function remain to be clarified. Several studies indicated extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase with its downstream effector AKT, and the phosphatase calcineurin as potential molecular substrates of extinction behavior. To test the involvement of these kinase and phosphatase activities in CBl-dependent extinction of conditioned fear behavior, conditioned CBI-deficient mice (CB1-super(-/-)) and wild-type littermates (CB1-super(+/+)) were sacrificed 30 min after recall of fear memory, and activation of ERKs, AKT, and calcineurin was examined by Western blot analysis in different brain regions. As compared with CB1-super(+/+), the nonreinforced tone presentation 24 h after auditory-cued fear conditioning led to lower levels of phosphorylated ERKs and/or calcineurin in the basolateral amygdala complex, ventromedial prefrontal cortex, dorsal hippocampus, and ventral hippocampus of CB1-super(-/-). In contrast, higher levels of phosphorylated p44 ERK and calcineurin were observed in the central nucleus of the amygdala of CB1-super(-/-). Phosphorylation of AKT was more pronounced in the basolateral amygdala complex and the dorsal hippocampus of CB1-super(-/-). We propose that the endogenous cannabinoid system modulates extinction of aversive memories, at least in part via regulation of the activity of kinases and phosphatases in a brain structure-dependent manner. _____
Title: Synaptic Gating and ADHD: A Biological Theory of Comorbidity of ADHD and Anxiety. Author(s): Levy, Florence, School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Randwick, NSW, Australia, f.levy@unsw.edu.au Address: Levy, Florence, School of Psychiatry, University of New South Wales, Prince of Wales Hospital, Randwick, NSW, Australia, 2031, f.levy@unsw.edu.au Source: Neuropsychopharmacology, Vol 29(9), Sep 2004. pp. 1589-1596. Publisher: United Kingdom: Nature Publishing Abstract: Attempted to derive a biologically based theory of comorbidity in Attention Deficit Hyperactivity Disorder (ADHD). Theoretical concepts and empirical studies were reviewed to determine whether the behavioral inhibition concept provided an understanding of biological processes involved in comorbidity in ADHD. Empirical studies of ADHD have shown comorbidity of ADHD and anxiety, while studies of behavioral inhibition tend to suggest independent disruptive and anxiety traits. This paradox can be resolved by an understanding of the dynamics of mesolimbic dopamine (DA) systems, where reward and delay of reinforcement are determined by tonic/phasic DA relationships, resulting in impulsive 'fearless' responses when impaired. On the other hand, comorbid anxiety is related to impaired synaptic processes, which selectively gate fear (or aggressive) responses from the amygdala at the accumbens. Monosynaptic convergence between prefrontal, hippocampal, and amygdala projection neurons at the accumbens allows the operation of a synaptic gating mechanism between prefrontal cortex (PFC), hippocampus, and amygdala. Impairment of this mechanism by lowered PFC inhibition allows greater amygdala input, and anxiety-related processes more impact, over the accumbens. In conclusion, a dual theory incorporating long-term tonic/phasic mesolimbic DA relationships and secondly impairment of PFC and hippocampal inputs to synaptic gating of anxiety at the accumbens has implications for comorbidity in ADHD, as well as for possible pharmacological interventions, utilizing either stimulant or axiolytic interventions. The use of DA partial agonists may also be of interest. _____
Title: Corticotropin-Releasing Factor Inhibits Maternal Aggression in Mice. Author(s): Gammie, Stephen C., Neuroscience Training Program, Department of Zoology, University of Wisconsin-Madison, Madison, WI, US, scgammie@wisc.edu; Negron, Alejandro, Neuroscience Training Program, Department of Zoology, University of Wisconsin-Madison, Madison, WI, US; Newman, Sarah M., Neuroscience Training Program, Department of Zoology, University of Wisconsin-Madison, Madison, WI, US; Rhodes, Justin S., Neuroscience Training Program, Department of Zoology, University of Wisconsin-Madison, Madison, WI, US Address: Gammie, Stephen C., Department of Zoology, University of Wisconsin, 1117 West Johnson Street, Madison, WI, US, scgammie@wisc.edu Source: Behavioral Neuroscience, Vol 118(4), Aug 2004. pp. 805-814. Publisher: US: American Psychological Assn Abstract: Lactating females that fiercely protect offspring exhibit decreased fear and anxiety. The authors tested whether decreased corticotropin-releasing factor (CRF), an activator of fear and anxiety, plays a functional role in maternal aggression. Intracerebroventricular (icv) injections of CRF (1.0 and 0.2 μg, but not 0.02 μg) significantly inhibited maternal aggression but not other maternal behaviors. The CRF antagonist D-Phe-CRF-sub(12-41) had no effect. Maternal aggression and icv CRF (0.2 μg) induced Fos in 11 of the same regions, including the lateral and medial septum, the bed nucleus of the stria terminalis, the medial and central amygdala, the periaqueductal gray, the dorsal raphe, and the locus coeruleus. These findings suggest that decreased CRF is necessary for maternal aggression and may act by altering brain activity in response to an intruder. _____
Title: Effects of Cyclic Adenosine Monophosphate Response Element Binding Protein Overexpression in the Basolateral Amygdala on Behavioral Models of Depression and Anxiety. Author(s): Wallace, Tanya L., Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, US; Stellitano, Kathryn E., Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, US; Neve, Rachael L., Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, US; Duman, Ronald S., Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, US Address: Duman, Ronald S., 34 Park Street, New Haven, CT, US Source: Biological Psychiatry, Vol 56(3), Aug 2004. pp. 151-160. Publisher: Netherlands: Elsevier Science Abstract: Background: Chronic antidepressant administration increases the cyclic adenosine monophosphate response element binding protein (CREB) in the amygdala, a critical neural substrate involved in the physiologic responses to stress, fear, and anxiety. Methods: To determine the role of CREB in the amygdala in animal models of depression and anxiety, a viral gene transfer approach was used to selectively express CREB in this region of the rat brain. Results: In the learned helplessness model of depression, induction of CREB in the basolateral amygdala after training decreased the number of escape failures, an antidepressant response. However, expression of CREB before training increased escape failures, and increased immobility in the forced swim test, depressive effects. Expression of CREB in the basolateral amygdala also increased behavioral measures of anxiety in both the open field test and the elevated plus maze, and enhanced cued fear conditioning. Conclusions: Taken together, these data demonstrate that CREB expression in the basolateral amygdala influences behavior in models of depression, anxiety, and fear. Moreover, in the basolateral amygdala, the temporal expression of CREB in relation to learned helplessness training, determines the qualitative outcome in this animal model of depression. _____
Title: Regulation of affect by the lateral septum: Implications for neuropsychiatry. Author(s): Sheehan, Teige P., Department of Psychology, Brown University, Providence, RI, US, teige_sheehan@brown.edu; Chambers, R. Andrew, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Inidanapolis, IN, US; Russell, David S., Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, US Address: Sheehan, Teige P., Department of Psychology, Brown University, P.O. Box 1853, Providence, RI, US, teige_sheehan@brown.edu Source: Brain Research Reviews, Vol 46(1), Aug 2004. pp. 71-117. Publisher: Netherlands: Elsevier Science Abstract: Substantial evidence indicates that the lateral septum (LS) plays a critical role in regulating processes related to mood and motivation. This review presents findings from the basic neuroscience literature and from some clinically oriented research, drawing from behavioral, neuroanatomical, electrophysiological, and molecular studies in support of such a role, and articulates models and hypotheses intended to advance our understanding of these functions. Neuroanatomically, the LS is connected with numerous regions known to regulate affect, such as the hippocampus, amygdala, and hypothalamus. Through its connections with the mesocorticolimbic dopamine system, the LS regulates motivation, both by stimulating the activity of midbrain dopamine neurons and regulating the consequences of this activity on the ventral striatum. Evidence that LS function could impact processes related to schizophrenia and other psychotic spectrum disorders, such as alterations in LS function following administration of antipsychotics and psychotomimetics in animals, will also be presented. The LS can also diminish or enable fear responding when its neural activity is stimulated or inhibited, respectively, perhaps through its projections to the hypothalamus. It also regulates behavioral manifestations of depression, with antidepressants stimulating the activity of LS neurons, and depression-like phenotypes corresponding to blunted activity of LS neurons; serotonin likely plays a key role in modulating these functions by influencing the responsiveness of the LS to hippocampal input. In conclusion, a better understanding of the LS may provide important and useful information in the pursuit of better treatments for a wide range of psychiatric conditions typified by disregulation of affective functions. _____
Title: Developmental Aspects of Addiction. Author(s): Booze, Rosemarie M., Department of Psychology, University of South Carolina, Columbia, SC, US, booze@sc.edu Address: Booze, Rosemarie M., Department of Psychology, University of South Carolina, 1512 Pendelton Street, Columbia, SC, US, booze@sc.edu Source: International Journal of Developmental Neuroscience, Vol 22(5-6), Aug-Oct 2004. Special issue: Developmental aspects of addiction. pp. 241-245. Publisher: Netherlands: Elsevier Science Abstract: In this special issue of the "International Journal of Developmental Neuroscience," the research programs of 15 groups are represented. All of this research utilizes animal models or isolated cells and tissue in an attempt to address fundamental biological processes that are otherwise difficult in humans. The specific compounds represented include the common illicit stimulants such as 3,4- methylenedioxymethamphetamine (MDMA), methamphetamine, and cocaine, as well as the widely abused licit substances, nicotine and alcohol. The focus of the first three articles is on two of the more commonly abused 'Club Drugs', 3,4-methylenedioxymethamphetamine and methamphetamine (MA). In contrast to the neonatal exposure modeling that characterizes the research on substituted amphetamines, the second set of four articles exemplify animal models that employ the prenatal exposure approach to address the developmental effects of cocaine and/or crack. The third segment of studies is focused on the more common licit drugs of nicotine and alcohol and showcases research encompassing prenatal through adolescent exposure periods. A fourth set of studies is focused on important developmental transitions in receptor development, sensitivities to reuptake inhibitors, and the functional emergence of the amygdala and the development of fear. _____
Title: Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups. Author(s): Moriceau, Stephanie, Department of Zoology, University of Oklahoma, Norman, OK, US, smoriceau@ou.edu; Roth, Tania L., Department of Zoology, University of Oklahoma, Norman, OK, US; Okotoghaide, Terri, Department of Zoology, University of Oklahoma, Norman, OK, US; Sullivan, Regina M., Department of Zoology, University of Oklahoma, Norman, OK, US Address: Moriceau, Stephanie, Department of Zoology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK, US, smoriceau@ou.edu Source: International Journal of Developmental Neuroscience, Vol 22(5-6), Aug-Oct 2004. Special issue: Developmental aspects of addiction. pp. 415-422. Publisher: Netherlands: Elsevier Science Abstract: In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN 12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control. _____
Title: Role of the Basolateral Amygdala in the Storage of Fear Memories across the Adult Lifetime of Rats. Author(s): Gale, Greg D., Department of Psychology, University of California, Los Angeles, CA, US, gale@psych.uda.edu; Anagnostaras, Stephan G., Department of Neurobiology, University of California, Los Angeles, CA, US; Godsil, Bill P., Department of Psychology, University of California, Los Angeles, CA, US; Mitchell, Shawn, Department of Psychology, University of California, Los Angeles, CA, US; Nozawa, Takashi, Department of Psychology, University of California, Los Angeles, CA, US; Sage, Jennifer R., Department of Psychology, University of California, Los Angeles, CA, US; Wiltgen, Brian, Department of Psychology, University of California, Los Angeles, CA, US; Fanselow, Michael S., Department of Psychology, University of California, Los Angeles, CA, US Address: Gale, Greg D., Department of Psychology, University of California, 405 Hilgard Avenue, Los Angeles, CA, US, gale@psych.uda.edu Source: Journal of Neuroscience, Vol 24(15), Aug 2004. pp. 3810-3815. Publisher: US: Society for Neuroscience Abstract: The basolateral amygdala (BLA) is intimately involved in the development of conditional fear. Converging lines of evidence support a role for this region in the storage of fear memory but do not rule out a time-limited role in the memory consolidation. To examine this issue, we assessed the stability of BLA contribution to fear memories acquired across the adult lifetime of rats. Fear conditioning consisted of 10 tone-shock pairings in one context (remote memory), followed 16 months later by 10 additional tone-shock pairings with a novel tone in a novel context (recent memory). Twenty-four hours after recent training, rats were given NMDA or sham lesions of the BLA. Contextual and tone freezing were independently assessed in individual test sessions. Sham-lesioned rats showed high and comparable levels of freezing across all context and tone tests. In contrast, BLA-lesioned rats displayed robust freezing deficits across both recent and remote tests. Subsequent open-field testing revealed no effects of BLA lesions on activity patterns in a dark open field or during bright light exposure. Lesioned rats were able to reacquire normal levels of context-specific freezing after an overtraining procedure (76 unsignaled shocks). Together, these findings indicate that BLA lesions do not disrupt freezing behavior by producing hyperactivity, an inability to suppress behavior, or an inability to freeze. Rather, the consistent pattern of freezing deficits at both training-to-lesion intervals supports a role for the BLA in the permanent storage of fear memory. _____
Title: Opioid Receptors in the Midbrain Periaqueductal Gray Regulate Extinction of Pavlovian Fear Conditioning. Author(s): McNally, Gavan P., School of Psychology, University of New South Wales, Sydney, NSW, Australia, g.mcnally@unsw.edu.au; Pigg, Michael, School of Psychology, University of New South Wales, Sydney, NSW, Australia; Weidemann, Gabrielle, School of Psychology, University of New South Wales, Sydney, NSW, Australia Address: McNally, Gavan P., School of Psychology, University of New South Wales, Sydney, NSW, Australia, 2052, g.mcnally@unsw.edu.au Source: Journal of Neuroscience, Vol 24(31), Aug 2004. pp. 6912-6919. Publisher: US: Society for Neuroscience Abstract: Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via nonreinforced presentations of the CS. Microinjection of the opioid receptor antagonist naloxone into the ventrolateral PAG (vlPAG) before nonreinforced CS presentations impaired development of extinction, but such microinjections at the end of extinction did not reinstate an already extinguished freezing CR. This role for opioid receptors in fear extinction was specific to the vlPAG because infusions of naloxone into the dorsal PAG did not impair fear extinction. Finally, the impairment of fear extinction produced by vlPAG infusions of naloxone was dose-dependent. These results show for the first time that the midbrain PAG contributes to fear extinction and specifically identify a role for vlPAG opioid receptors in the acquisition but not the expression of such extinction. Taken together with our previous findings, we suggest that, during fear conditioning, activation of vlPAG opioid receptors contributes to detection of the discrepancy between the actual and expected outcome of the conditioning trial. vlPAG opioid receptors regulate the learning that accrues to the CS and other stimuli present on a trial because they instantiate an associative error correction process influencing US information reaching the site of CS-US convergence in the amygdala. During nonreinforcement, this vlPAG opioid receptor contribution signals extinction. _____
Title: Neurobiological Bases of Individual Differences in Emotional and Stress Responsiveness: High responders--low responders model. Author(s): Kabbaj, Mohamed, Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, US, Mohamed.Kabbaj@med.fsu.edu Address: Kabbaj, Mohamed, Department of Biomedical Sciences, College of Medicine, Florida State University, 520 Building 127, Tallahassee, FL, US, Mohamed.Kabbaj@med.fsu.edu Source: Archives of Neurology, Vol 61(7), Jul 2004. pp. 1009-1012. Publisher: US: American Medical Assn Abstract: Emotion, as defined by psychologists, is a strong and complex feeling state that is consciously perceived, like anger, fear, happiness, or love. Although we do not have direct animal models of emotions, we have the tools to study in animals some of the variables that represent components of these human traits, including emotional responsiveness and stress reactivity. It is believed that animal differences in emotional reactivity involve some of the same neuronal circuitry that is relevant in humans. This circuitry includes the paraventricular nucleus of the hypothalamus (PVN), monoaminergic nuclei in the midbrain, amygdala, prefrontal cortex, hippocampus, and other limbic and limbic-associated areas. This circuitry determines how an individual perceives a stress and copes with it. It is a disruption of this circuitry that is responsible for why some individuals develop anxiety and major depressive disorders. In this article we describe what is known about this emotional circuitry among animals that differ in emotional reactivity and stress responsiveness. _____
Title: Axonal connections from posterior paralaminar thalamic neurons to basomedial amygdaloid projection neurons to the lateral entorhinal cortex in rats. Author(s): Linke, R., Institut für Anatomic, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany, ruediger.linke@medizin.uni-magdeburg.de; Faber-Zuschratter, H., Institut für Anatomic, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany; Seidenbecher, T., Institut für Physiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany; Pape, H. -C., Institut für Physiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany Address: Linke, R., Institut fur Anatomic, Otto-von-Guericke Universitat Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany, ruediger.linke@medizin.uni-magdeburg.de Source: Brain Research Bulletin, Vol 63(6), Jul 2004. pp. 461-469. Publisher: Netherlands: Elsevier Science Abstract: Stimulation of amygdaloid nuclei and emotionally relevant stimuli are known to influence the induction and maintenance of long-term potentiation in the hippocampal formation and the formation of long-term declarative memories. Because the thalamic projection from the posterior paralaminar thalamic nuclei is an important sensory afferent projection to amygdaloid nuclei mediating the fast acquisition of fear-potentiated behavior, we were interested in verifying whether this projection establishes synaptic contacts on amygdala neurons that project to the hippocampal formation. Thalamic afferents were labeled with the anterograde tracer Phaseolus vulgaris leucoagglutinin and amygdalo-hippocampal neurons were identified by injection of the retrograde tracer Fluorogold into the lateral entorhinal cortex. A massive overlap of both projection systems was observed especially in the anterior basomedial nucleus of the amygdala. Light microscopic examination revealed that single anterogradely labeled boutons were in close apposition to retrogradely labeled neurons suggesting synaptic contacts. The occurrence of such synaptic contacts was confirmed with electron microscopy. However, despite the massive overlap of anterogradely labeled axons and retrogradely labeled neurons observed at the light microscopic level, electron microscopy revealed that only 10% of all labeled profiles make direct contacts on each other; anterogradely labeled boutons predominantly contacted unlabeled profiles but synapses with direct contact between labeled profiles were rare. Altogether the findings demonstrate that the thalamic connection with the basomedial nucleus of the amygdala may represent an anatomical substrate for modulating amygdala output to the hippocampal formation. _____
Title: NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala. Author(s): Goosens, Ki A., Department of Psychology, University of Michigan, Ann Arbor, MI, US; Maren, Stephen, Department of Psychology, University of Michigan, Ann Arbor, MI, US, maren@umich.edu Address: Maren, Stephen, Department of Psychology, University of Michigan, Ann Arbor, MI, US, maren@umich.edu Source: European Journal of Neuroscience, Vol 20(2), Jul 2004. pp. 537-548. Publisher: United Kingdom: Blackwell Publishing Abstract: We examined the contribution of N-methyl-D-aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist ±-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.
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