Faculty Bibliography

Mother-infant attachment is facilitated in altricial rodents through unique neural mechanisms that include impaired neonatal fear conditioning until the time that pups first begin to leave the nest (sensitive period). Here, we confirmed the developmental emergence of odor fear conditioning in neonatal rat pups, and examined synaptic plasticity of inputs to the basolateral amygdala in vitro. Coronal slices through the amygdala were obtained from sensitive (<10 days) and post-sensitive (>10, <19 days) period pups. Field potentials were recorded in the basolateral amygdala in response to stimulation of either the external capsule (neocortical inputs) or fibers from the cortical nucleus of the amygdala (olfactory inputs). The effects of tetanic stimulation were examined in each pathway. In both pathways, tetanic stimulation induce significant long-term synaptic plasticity in post-sensitive period pups, but no significant plasticity in sensitive period pups incapable of learning odor aversions. GABA(A) receptor blockade in post-sensitive period slices reverts synaptic plasticity to sensitive period characteristics. The results suggest that sensitive period deficits in fear conditioning may be related to impaired amygdala synaptic plasticity and the immature state of GABAergic inhibition and/or its modulation in the neonatal amygdala

BACKGROUND: Pediatric anxiety disorders, although highly prevalent, are understudied with little known about their pathophysiology. Intolerance of uncertainty (IU) is a trait associated with worry, a key characteristic of these disorders. Neural responses to uncertainty in healthy subjects involve the same frontal-limbic circuits that are hyper-responsive in pediatric anxiety. As such, the present study examines the relationship between IU and neural responses to uncertainty in anxious adolescents. METHODS: Sixteen adolescents (ages 13-17) diagnosed with generalized anxiety disorder and/or social phobia (ANX) and 13 non-anxious control subjects completed a decision-making task while functional magnetic resonance imaging scans were acquired. RESULTS: The ANX group endorsed greater task-related anxiety and less certainty than control subjects on a post-task questionnaire. Compared with control subjects, the ANX group did not demonstrate hyper-responsivity of brain regions as hypothesized. Across groups, IU was positively correlated with activity in several frontal and limbic regions. Further analyses identified subgroups within the ANX group: those with high IU activated frontal/limbic regions, whereas those with low IU and less anxiety during the task deactivated the same regions in response to uncertainty. CONCLUSIONS: Results substantiate the hypothesized link between IU and neural responses to uncertainty in some adolescents with anxiety disorders. Our findings, if replicated, suggest that trait measures, such as IU, can significantly improve our understanding of the neurobiological basis of pediatric anxiety disorders

In this study, a resting-state fMRI based classifier, for the first time, was proposed and applied to discriminate children with attention-deficit/hyperactivity disorder (ADHD) from normal controls. On the basis of regional homogeneity (ReHo), a mapping of brain function at resting state, PCA-based Fisher discriminative analysis (PC-FDA) was trained to build a linear classifier. Permutation test was then conducted to identify the brain areas with the most significant contribution to the final discrimination. Experimental results showed a correct classification rate of 85% using a leave-one-out cross-validation. Moreover, some highly discriminative brain regions, like the prefrontal cortex and anterior cingulate cortex, well confirmed the previous findings on ADHD. Interestingly, some important but less reported regions such as the thalamus were also identified. We conclude that the classifier, using resting-state brain function as classification feature, has potential ability to improve current diagnosis and treatment evaluation of ADHD.

The purpose of this study was to test the feasibility and short-term outcomes of Asthma: It's a Family Affair!, a school-based intervention for adolescents with asthma and their caregivers. Twenty-four ethnic minority families with a middle school student with asthma were randomized to immediate intervention or no-treatment control. Intervention students received six group sessions on prevention and management of asthma. Caregivers received five group sessions teaching child-rearing skills to support the youth's autonomy and asthma self-management. All students attended all sessions; caregivers attended an average of three. Two months post-intervention, relative to controls, intervention caregivers reported better problem-solving with children. Intervention students were more responsible for carrying medication, took more prevention steps, and woke fewer nights from asthma. The intervention resulted in positive short-term changes in family relations, asthma management by students, and health status

The 'therapeutic misconception' describes a process whereby research volunteers misinterpret the intentions of researchers and the nature of clinical research. This misinterpretation leads research volunteers to falsely attribute a therapeutic potential to clinical research, and compromises informed decision making, therefore compromising the ethical integrity of a clinical experiment. We review recent evidence from the neurobiology of social cognition to provide a novel framework for thinking about the therapeutic misconception. We argue that the neurobiology of social cognition should be considered in any ethical analysis of how people make decisions about participating in clinical trials. The neurobiology of social cognition also suggests how the complicated dynamics of the doctor-patient relationship may unavoidably interfere with the process of obtaining informed consent. Following this argument we suggest new ways to prevent or at least mitigate the therapeutic misconception

Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is greater when mice are habituated on longer timescales. Second, the specificity of the memory (degree of cross-habituation to similar stimuli) also depends on induction timescale. Third, we demonstrate a pharmacological double dissociation between the glutamatergic mechanisms underlying short- and long-timescale odor habituation. LY341495, a class II/III metabotropic glutamate receptor antagonist, blocked habituation only when the induction timescale was short. Conversely, MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, prevented habituation only when the timescale was long. Finally, whereas short-timescale odor habituation is mediated within the anterior piriform cortex, infusion of MK-801 into the olfactory bulbs prevented odor habituation only at longer timescales. Thus, we demonstrate two neural mechanisms underlying simple olfactory learning, distinguished by their persistence and specificity, mediated by different olfactory structures and pharmacological effectors, and differentially utilized based solely on the timescale of odor presentation

The organizational social context in which mental health services are provided is believed to affect the adoption and implementation of evidence-based practices (EBPs) as well as the quality and outcomes of the services. A fully developed science of implementation effectiveness requires conceptual models that include organizational social context and tools for assessing social context that have been tested in a broad cross-section of mental health systems. This paper describes the role of organizational social context in services and implementation research and evaluates a comprehensive contextual measure, labeled Organizational Social Context (OSC), designed to assess the key latent constructs of culture, climate and work attitudes. The psychometric properties of the OSC measure were assessed in a nationwide study of 1,154 clinicians in 100 mental health clinics with a second-order confirmatory factor analysis of clinician responses, estimates of scale reliabilities, and indices of within-clinic agreement and between-clinic differences among clinicians. Finally, the paper illustrates the use of nationwide norms in describing the OSC profiles of individual mental health clinics and examines the cross-level association of organizational-level culture and climate with clinician-level work attitudes.

The present study incorporates organizational theory and organizational characteristics in examining issues related to the successful implementation of mental health services. Following the theoretical foundations of socio-technical and cultural models of organizational effectiveness, organizational climate, culture, legal and service structures, and workforce characteristics are examined as correlates of therapist turnover and new program sustainability in a nationwide sample of mental health clinics. Results of General Linear Modeling (GLM) with the organization as the unit of analysis revealed that organizations with the best climates as measured by the Organizational Social Context (OSC) profiling system, had annual turnover rates (10%) that were less than half the rates found in organizations with the worst climates (22%). In addition, organizations with the best culture profiles sustained new treatment or service programs over twice as long (50 vs. 24 months) as organizations with the worst cultures. Finally, clinics with separate children's services units had higher turnover rates than clinics that served adults and children within the same unit. The findings suggest that strategies to support the implementation of new mental health treatments and services should attend to organizational culture and climate, and to the compatibility of organizational service structures with the demand characteristics of treatments.