Faculty Bibliography

N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction

Infant rats learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver to receive protection and food. With maturity, a more 'adult-like' learning system emerges that includes the amygdala and avoidance/fear learning. The attachment and 'adult-like' systems appear to co-exist in older pups with maternal presence engaging the attachment system by lowering corticosterone (CORT). Specifically, odor-shock conditioning (11 odor-0.5 mA shock trials) in 12-day-old pups results in an odor aversion, although an odor preference is learned if the mother is present during conditioning. Here, we propose a mechanism to explain pups ability to 'switch' between the dual learning systems by exploring the effect of maternal presence on hypothalamic paraventricular nucleus (PVN) neural activity, norepinephrine (NE) levels and learning. Maternal presence attenuates both PVN neural activity and PVN NE levels during odor-shock conditioning. Intra-PVN NE receptor antagonist infusion blocked the odor aversion learning with maternal absence, while intra-PVN NE receptor agonist infusion permitted odor aversion learning with maternal presence. These data suggest maternal control over pup learning acts through attenuation of PVN NE to reduce the CORT required for pup odor aversion learning. Moreover, these data also represent pups' continued maternal dependence for nursing, while enabling aversion learning outside the nest to prepare for pups future independent living

BACKGROUND: The Social Communication Questionnaire (SCQ), formerly the Autism Screening Questionnaire (ASQ), is based on a well-validated parent interview, the Autism Diagnostic Interview (ADI). It has shown promise as a screening measure for autism spectrum disorders (ASDs) in a research-referred older sample, though recent studies with younger children reported lower sensitivities when using the suggested cutoff of > or = 15 to differentiate ASDs from children with nonspectrum disorders (NS). METHODS: Diagnostic discrimination of the SCQ was evaluated alone and in combination with the ADOS (Autism Diagnostic Observation Schedule) in a clinical and research-referred sample of 590 children and adolescents (2 to 16 years), with best estimate consensus diagnoses of autism, pervasive developmental disorder, not otherwise specified (PDD-NOS) and non-ASD disorders. The SCQ was completed before the evaluation in most cases. Performance of the SCQ was also compared with the Autism Diagnostic Interview - Revised (ADI-R). RESULTS: Absolute scores and sensitivity in the younger children and specificity for all groups were lower than reported in the original study. Using receiver operating curves (ROC) to examine the area under the curve (AUC), the SCQ was more similar to the ADI-R total score in differentiating ASD from NS disorders in the older (8-10, >11) than younger age groups (<5, 5-7). Lowering the cutoff score in the 2 younger groups improved sensitivity, with specificity remaining relatively low in all groups. Using the SCQ in combination with the ADOS resulted in improved specificity. Diagnostic discrimination was best using the ADI-R and ADOS in combination. CONCLUSIONS: Those interested in using the SCQ should consider adjusting cutoff scores according to age and purpose, and using it in combination with another measure. Sensitivity or specificity may be prioritized for research or screening depending on goals

CONTEXT: Evidenced-based treatment trials for adolescents with bulimia nervosa are largely absent. OBJECTIVE: To evaluate the relative efficacy of family-based treatment (FBT) and supportive psychotherapy (SPT) for adolescents with bulimia nervosa. DESIGN: Randomized controlled trial. SETTING: The University of Chicago from April 1, 2001, through June 30, 2006. PARTICIPANTS: Eighty patients, aged 12 to 19 years, with a DSM-IV diagnosis of bulimia nervosa or a strict definition of partial bulimia nervosa. INTERVENTIONS: Twenty outpatient visits over 6 months of FBT or SPT. Participants were followed up at 6 months posttreatment. MAIN OUTCOME MEASURES: Abstinence from binge-and-purge episodes as measured by the Eating Disorder Examination. Secondary outcome measures were Eating Disorder Examination binge-and-purge frequency and Eating Disorder Examination subscale scores. RESULTS: Forty-one patients were assigned to FBT and 39 to SPT. Categorical outcomes at posttreatment demonstrated that significantly more patients receiving FBT (16 [39%]) were binge-and-purge abstinent compared with those receiving SPT (7 [18%]) (P = .049). Somewhat fewer patients were abstinent at the 6-month follow-up; however, the difference was statistically in favor of FBT vs SPT (12 patients [29%] vs 4 patients [10%]; P = .05). Secondary outcome assessment, based on random regression analysis, revealed main effects in favor of FBT on all measures of eating pathological features (P = .003 to P = .03 for all). CONCLUSIONS: Family-based treatment showed a clinical and statistical advantage over SPT at posttreatment and at 6-month follow-up. Reduction in core bulimic symptoms was also more immediate for patients receiving FBT vs SPT

In this investigation, the socio-communicative skills of 29 children with Williams syndrome aged 2 (1/2) to 5 (1/2) years were examined using the Autism Diagnostic Observation Schedule (ADOS) Module 1. Most of the participants showed socio-communicative difficulties. Approximately half of the participants were classified by the ADOS algorithm as 'autism spectrum.' Three participants were classified 'autism.' Difficulties with pointing, gestures, giving, showing, and eye contact were present for more than half of the participants, with many also showing difficulties with initiation and response to joint attention and with integration of gaze with other behaviors. Expressive and receptive language abilities of the children with Williams syndrome classified 'autism spectrum' were weaker than for children classified nonspectrum, but expressive and receptive language level did not account for the socio-communicative difficulties. Implications for our understanding of the socio-communicative abilities of young children with Williams syndrome and diagnostic practices regarding dual diagnosis are discussed

Anterior cingulate cortex (ACC) is a nexus of information processing and regulation in the brain. Reflecting this central role, ACC is structurally and functionally heterogeneous, a fact long appreciated in studies of non-human primates. Human neuroimaging studies also recognize this functional heterogeneity, with meta-analyses and task-based studies demonstrating the existence of motor, cognitive and affective subdivisions. In contrast to task-based approaches, examinations of resting-state functional connectivity enable the characterization of task-independent patterns of correlated activity. In a novel approach to understanding ACC functional segregation, we systematically mapped ACC functional connectivity during rest. We examined patterns of functional connectivity for 16 seed ROIs systematically placed throughout caudal, rostral, and subgenual ACC in each hemisphere. First, our data support the commonly observed rostral/caudal distinction, but also suggest the existence of a dorsal/ventral functional distinction. For each of these distinctions, more fine-grained patterns of differentiation were observed than commonly appreciated in human imaging studies. Second, we demonstrate the presence of negatively predicted relationships between distinct ACC functional networks. In particular, we highlight negative relationships between rostral ACC-based affective networks (including the 'default mode network') and dorsal-caudal ACC-based frontoparietal attention networks. Finally, interhemispheric activations were more strongly correlated between homologous regions than in non-homologous regions. We discuss the implications of our work for understanding ACC function and potential applications to clinical populations

Parkinson's disease (PD) typically manifests with asymmetric motor symptom onset. Ventricular enlargement, a nonspecific measure of brain atrophy, has been associated with cognitive decline in PD, but not with motor symptom asymmetry. Asymmetrical ventricular enlargement on magnetic resonance images was explored in a monozygotic twin pair discordant for PD and in nine healthy monozygotic twin pairs. The left-right lateral ventricular volumetric difference of the PD-twin was greater than that of his twin and all other healthy twins, with the larger ventricle observed contralateral to the more symptomatic side. Moreover, the lateral ventricle asymmetry difference between twin pairs was significantly higher for the discordant PD-twin pair than for the healthy twin pairs. This is the first report to suggest the presence of asymmetrical ventricular enlargement in PD, findings that may be worthy of further study.

Increasing rates of obesity have alarmed health officials and prompted much public dialogue. While the factors leading to obesity are numerous, an inability to control intake of freely available food is central to the problem. In order to understand this, we need to better define the mechanisms by which the brain regulates food intake, and why it is often difficult to control consumption. From this point of view, it seems valuable to consider the commonalities between food intake and drug abuse. While research in the two fields has historically emphasized different neural substrates, recent data have increased interest in better defining elements that may underlie both drug addiction and obesity. Here we discuss some of these shared elements with an emphasis on emerging areas of research that better define common mechanisms leading to overconsumption.