Faculty Bibliography

Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed

The ability to specify differential predictions is a mark of a scientific models' value. State regulation deficits (SRD) and delay aversion (DAv) have both been hypothesized as context-dependent dynamic dysfunctions in ADHD. However, to date there has been no systematic comparison of their common and unique elements. Here we review these hypotheses-and describe the core and secondary manifestations of the two constructs and review evidence in support of them. Second, we focus on what are seen as the hallmark indicators of the two deficits-preference of small immediate over large delayed rewards for DAv and the slow event rate effect for SRD. We describe the overlap between these two manifestations and then explore how experimental manipulations and the analysis of neuropsychological and physiological mediators of effects can allow us to differentiate these two patterns of neuropsychological dysfunction on the basis of specific predictions. Finally, we highlight the implications of neuropsychological heterogeneity for the practical implementation of tests of DAv and SRD

BACKGROUND: Irritability is prevalent and impairing in pediatric bipolar disorder (BD) but has been minimally studied using neuroimaging techniques. We used magnetoencephalography (MEG) to study theta band oscillations in the anterior cingulate cortex (ACC) during frustration in BD youth. ACC theta power is associated with attention to emotional stimuli, and the ACC may mediate responses to frustrating stimuli. METHODS: We used the affective Posner task, an attention paradigm that uses rigged feedback to induce frustration, to compare 20 medicated BD youth (14.9+/-2.0 years; 45% male) and 20 healthy controls (14.7+/-1.7 years; 45% male). MEG measured neuronal activity after negative and positive feedback; we also compared groups on reaction time, response accuracy, and self-reported affect. Patients met strict DSM-IV BD criteria and were euthymic. Controls had no psychiatric history. RESULTS: BD youth reported more negative affective responses than controls. After negative feedback, BD subjects, relative to controls, displayed greater theta power in the right ACC and bilateral parietal lobe. After positive feedback, BD subjects displayed lower theta power in the left ACC than did controls. Correlations between MEG, behavior, and affect were nonsignificant. CONCLUSION: In this first MEG study of BD youth, BD youth displayed patterns of theta oscillations in the ACC and parietal lobe in response to frustration-inducing negative feedback that differed from healthy controls. These data suggest that BD youth may display heightened processing of negative feedback and exaggerated self-monitoring after frustrating emotional stimuli. Future studies are needed with unmedicated bipolar youth, and comparison ADHD and anxiety groups.

Severe psychological stress in the first trimester of pregnancy increases the risk of schizophrenia in the offspring. To begin to investigate the role of glucocorticoid receptors in this association, we determined the effects of the glucocorticoid dexamethasone (2 mg/kg), administered to pregnant rats on gestation days 6-8, on maternal behaviors and schizophrenia-relevant behaviors in the offspring. Dams receiving dexamethasone exhibited increased milk ejection bouts during nursing. Offspring of dexamethasone-treated dams (DEX) showed decreased juvenile social play and a blunted acoustic startle reflex in adolescence and adulthood, effects that were predicted by frequency of milk ejections in the dams. DEX offspring also showed increased prepulse inhibition of startle and reduced amphetamine-induced motor activity, effects not correlated with maternal behavior. It is postulated that over-stimulation of receptors targeted by glucocorticoids in the placenta or other maternal tissues during early gestation can lead to psychomotor and social behavioral deficits in the offspring. Moreover, some of these deficits may be mediated by alterations in postnatal maternal behavior and physiology produced by early gestational exposure to excess glucocorticoids. (c) 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:121-132, 2010

OBJECTIVE: To document prospective weight and anthropometric changes in children and adolescents during the first 12 weeks of treatment with risperidone and evaluate metabolic outcomes including plasma leptin levels. METHOD: Eight patients with psychotic disorders (ages 11-17) who had started risperidone (mean: 1.80 mg/day; sd = 1.04) in the prior 4 weeks participated in this observational study. Fasting morning blood samples were obtained at baseline and week 8 to assess glucose, leptin, cortisol, insulin, and triglycerides. Measures of body mass index (BMI), weight, waist and hip circumference, blood pressure, and heart rate were obtained weekly. RESULTS: Participants increased in mean weight (4.16 kg; sd = 4.36; p = 0.03) and BMI (1.47 kg/m(2); sd = 1.53; p = 0.03) with five out of eight gaining at least 7% of baseline body weight. They had a 4.03 cm (sd = 3.82; p = 0.02) increase in waist circumference and a 5.17 cm (sd = 3.68; p = 0.01) increase in hip circumference. Leptin trended higher, but did not reach statistical significance. There were no significant changes in glucose, insulin, cortisol, blood pressure, or heart rate. CONCLUSION: Subjects experienced significant increases in weight, BMI, hip and waist circumference during the first 3 months of treatment. Better powered research with more advanced anthropometric assessment is warranted to further elucidate mechanisms of antipsychotic associated weight gain in youth

BACKGROUND: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. METHODS: Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. RESULTS: In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. LIMITATIONS: The small sample size may have affected our ability to detect additional group differences. CONCLUSION: When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD

Aggressive patients often target psychiatrists and psychiatric residents, yet most clinicians are insufficiently trained in violence risk assessment and management. Consequently, many clinicians are reluctant to diagnose and treat aggressive and assaultive features in psychiatric patients and instead focus attention on other axis I mental disorders with proven pharmacological treatment in the hope that this approach will reduce the aggressive behavior. Unclear or nonexistent reporting policies or feelings of self-blame may impede clinicians from reporting assaults, thus limiting our knowledge of the impact of, and best response to, aggression in psychiatric patients. The authors pre-sent the case of a young adult inpatient with a long history of antisocial and assaultive behavior who struck and injured a psychiatric resident. With this case in mind, the authors discuss the diagnostic complexities related to violent patients, the importance of assessing violence risk when initially evaluating a patient, and the relevance of risk assessment for treatment considerations and future management. This report illustrates common deficiencies in the prevention of violence on inpatient psychiatric units and in the reporting and response to an assault, and has implications for residency and clinician training

Historical and psychophysical literature has demonstrated a perceptual interplay between olfactory and auditory stimuli-the neural mechanisms of which are not understood. Here, we report novel findings revealing that the early olfactory code is subjected to auditory cross-modal influences. In vivo extracellular recordings from the olfactory tubercle, a trilaminar structure within the basal forebrain, of anesthetized mice revealed that olfactory tubercle single units selectively respond to odors-with 65% of units showing significant odor-evoked activity. Remarkably, 19% of olfactory tubercle single units also showed robust responses to an auditory tone. Furthermore, 29% of single units tested displayed supraadditive or suppressive responses to the simultaneous presentation of odor and tone, suggesting cross-modal modulation. In contrast, olfactory bulb units did not show significant responses to tone presentation nor modulation of odor-evoked activity by tone-suggesting a lack of olfactory-auditory convergence upstream from the olfactory tubercle. Thus, the tubercle presents itself as a source for direct multimodal convergence within an early stage of odor processing and may serve as a seat for psychophysical interactions between smells and sounds