Faculty Bibliography

Despite the nosological distinction between bipolar disorder and schizophrenia, there is increasing evidence that these conditions share phenomenological characteristics. To examine the similarities in their patterns of cognitive impairment, we conducted a meta-analysis from 12 studies of Early Onset Schizophrenia (EOS) and 12 studies of Pediatric Bipolar Disorder (PBD). We found that individuals with PBD suffer from cognitive deficits (e.g., verbal learning and memory, processing speed, or executive control) that are milder but similar in nature to those of patients with EOS. Qualitative similarities between the neuropsychological profiles produced by these groups of patients might represent a 'continuum of psychosis' or reflect some degree of genetic biological overlap

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted 'U-shape'), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples

Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective 'hubs' in the brain-the anterior cingulate and precuneus-each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses

Motor inhibition is among the most commonly studied executive functions in attention-deficit/hyperactivity disorder (ADHD). Imaging studies using probes of motor inhibition such as the stop signal task (SST) consistently demonstrate ADHD-related dysfunction within a right-hemisphere fronto-striatal network that includes inferior frontal gyrus and pre-supplementary motor area. Beyond findings of focal hypo- or hyper-function, emerging models of ADHD psychopathology highlight disease-related changes in functional interactions between network components. Resting state fMRI (R-fMRI) approaches have emerged as powerful tools for mapping such interactions (i.e., resting state functional connectivity, RSFC), and for relating behavioral and diagnostic variables to network properties. We used R-fMRI data collected from 17 typically developing controls (TDC) and 17 age-matched children with ADHD (aged 8-13 years) to identify neural correlates of SST performance measured outside the scanner. We examined two related inhibition indices: stop signal reaction time (SSRT), indexing inhibitory speed, and stop signal delay (SSD), indexing inhibitory success. Using 11 fronto-striatal seed regions-of-interest, we queried the brain for relationships between RSFC and each performance index, as well as for interactions with diagnostic status. Both SSRT and SSD exhibited connectivity-behavior relationships independent of diagnosis. At the same time, we found differential connectivity-behavior relationships in children with ADHD relative to TDC. Our results demonstrate the utility of RSFC approaches for assessing brain/behavior relationships, and for identifying pathology-related differences in the contributions of neural circuits to cognition and behavior.