Faculty Bibliography

Although it is believed that different types of memories are localized in discreet regions of the brain, concrete experimental evidence of the existence of such engrams is often elusive. Despite being one of the best characterized memory systems of the brain, the question of where fear memories are localized in the brain remains a hotly debated issue. Here, we combine site-specific behavioral pharmacology with multisite electrophysiological recording techniques to show that the lateral nucleus of the amygdala, long thought to be critical for the acquisition of fear memories, is also an essential locus of fear memory storage

Research on the neural systems underlying emotion in animal models over the past two decades has implicated the amygdala in fear and other emotional processes. This work stimulated interest in pursuing the brain mechanisms of emotion in humans. Here, we review research on the role of the amygdala in emotional processes in both animal models and humans. The review is not exhaustive, but it highlights five major research topics that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory, emotional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation

BACKGROUND: Emotion-related perturbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral measures of modulation of response errors. METHODS: A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescents. Performance accuracy, saccade latency, and peak velocity of incorrect responses were analyzed. RESULTS: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However, modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions (saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups. CONCLUSIONS: These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional interference on directed action in adolescents with mood and anxiety disorders. Furthermore, neural mechanisms can now be examined by using this task paired with functional neuroimaging.

BACKGROUND: The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) among adults by using drug-placebo response curve methods. METHODS: We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. RESULTS: Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. CONCLUSION: From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently comorbid and overlapping diagnoses. To move beyond diagnosis toward unique pathophysiology, we evaluated both ADHD and BPD children for neurologic examination abnormalities (NEAs) in comparison with normal control (NC) children. METHODS: We performed the Revised Physical and Neurological Examination for Soft Signs in three groups (ADHD, BPD, NC). Then, a rater blind to diagnosis evaluated their motor performance. Results were analyzed with a multiple analysis of covariance. RESULTS: Subjects with ADHD were impaired on repetitive task reaction time. In contrast, pediatric BPD subjects, both with and without comorbid ADHD, were impaired on sequential task reaction time. CONCLUSIONS: This differential pattern of NEAs by diagnosis suggests pathophysiologic differences between ADHD and BPD in children. Repetitive motor performance requires inhibition of nonrelevant movements; ADHD subjects' impairment in this domain supports the hypothesis that ADHD involves a core deficit of fronto-striato-basal ganglia neurocircuitry. In contrast, BPD subjects' impaired sequential motor performance is consistent with behavioral data showing impaired attentional set-shifting and reversal learning in BPD subjects. Further study, going beyond symptom description to determine pathophysiologic differences, is required to refine neuronal models of these often comorbid diagnoses

BACKGROUND: Theories in affective neuroscience suggest that mood disorders involve perturbations in attention-emotion interactions. We tested the hypothesis that frustration adversely impacts attention and behavior in children with bipolar disorder (BPD). METHODS: Thirty-five children with BPD and 26 normal control subjects completed: 1) a Posner attention task with feedback but no contingencies; 2) an affective Posner with contingencies; and 3) an affective Posner that used rigged feedback to induce frustration. Reaction time (RT) and event-related potential (ERP) data were collected. RESULTS: At baseline (task 1), there were no between-group differences in behavior or ERPs. Children with BPD exhibited reduced parietal P3 amplitude on task 3 only. On trials occurring after negative feedback, control subjects showed decreased RT when contingencies were introduced (task 2), whereas BPD subjects did not. CONCLUSIONS: The introduction of contingencies was associated with impaired performance of children with BPD, suggesting deficits in their ability to adapt to changing contingencies. In addition, frustration was associated with disrupted attention allocation in children with BPD. We hypothesize that children with BPD inappropriately deployed attention to their internal frustration rather than to the task, causing impaired performance.

PURPOSE AND BACKGROUND: Intersex cortical and functional asymmetry is an ongoing topic of investigation. In this pilot study, we sought to determine the influence of acoustic scanner noise and sex on auditory and language cortical activation patterns of the dominant hemisphere. MATERIALS AND METHODS: Echoplanar functional MR imaging (fMRI; 1.5T) was performed on 12 healthy right-handed subjects (6 men and 6 women). Passive text listening tasks were employed in 2 different background acoustic scanner noise conditions (12 sections/2 seconds TR [6 Hz] and 4 sections/2 seconds TR [2 Hz]), with the first 4 sections in identical locations in the left hemisphere. Cross-correlation analysis was used to construct activation maps in subregions of auditory and language relevant cortex of the dominant (left) hemisphere, and activation areas were calculated by using coefficient thresholds of 0.5, 0.6, and 0.7. RESULTS: Text listening caused robust activation in anatomically defined auditory cortex, and weaker activation in language relevant cortex of all 12 individuals. As a whole, there was no significant difference in regional cortical activation between the 2 background acoustic scanner noise conditions. When sex was considered, men showed a significantly (P < .01) greater change in left hemisphere activation during the high scanner noise rate condition than did women. This effect was significant (P < .05) in the left superior temporal gyrus, the posterior aspect of the left middle temporal gyrus and superior temporal sulcus, and the left inferior frontal gyrus. CONCLUSION: Increase in the rate of background acoustic scanner noise caused increased activation in auditory and language relevant cortex of the dominant hemisphere in men compared with women where no such change in activation was observed. Our preliminary data suggest possible methodologic confounds of fMRI research and calls for larger investigations to substantiate our findings and further characterize sex-based influences on hemispheric activation patterns

OBJECTIVE: To review recent progress in child and adolescent psychiatric epidemiology in the area of prevalence and burden. METHOD: The literature published in the past decade was reviewed under two headings: methods and findings. RESULTS: Methods for assessing the prevalence and community burden of child and adolescent psychiatric disorders have improved dramatically in the past decade. There are now available a broad range of interviews that generate DSM and ICD diagnoses with good reliability and validity. Clinicians and researchers can choose among interview styles (respondent based, interviewer based, best estimate) and methods of data collection (paper and pencil, computer assisted, interviewer or self-completion) that best meet their needs. Work is also in progress to develop brief screens to identify children in need of more detailed assessment, for use by teachers, pediatricians, and other professionals. The median prevalence estimate of functionally impairing child and adolescent psychiatric disorders is 12%, although the range of estimates is wide. Disorders that often appear first in childhood or adolescence are among those ranked highest in the World Health Organization's estimates of the global burden of disease. CONCLUSIONS: There is mounting evidence that many, if not most, lifetime psychiatric disorders will first appear in childhood or adolescence. Methods are now available to monitor youths and to make early intervention feasible.

OBJECTIVE: Patients with bipolar disorder become hyperhedonic when manic and anhedonic when depressed; therefore, it is important to test whether patients with bipolar disorder show deficits on behavioral paradigms exploring reward/punishment mechanisms. METHOD: A probabilistic response-reversal task was administered to 24 bipolar children and 25 comparison subjects. RESULTS: Patients made more errors during probabilistic reversal, took longer to learn the new reward object, and were less likely to meet the learning criterion. CONCLUSIONS: Children with bipolar disorder may have a reversal learning deficit.