Psychiatry - Research Publications
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ItemNeurodevelopmental correlates of the emerging adult self(ELSEVIER SCI LTD, 2019-04)The self-concept - the set of beliefs that a person has about themselves - shows significant development from adolescence to early adulthood, in parallel with brain development over the same period. We sought to investigate how age-related changes in self-appraisal processes corresponded with brain network segregation and integration in healthy adolescents and young adults. We scanned 88 participants (46 female), aged from 15 to 25 years, as they performed a self-appraisal task. We first examined their patterns of activation to self-appraisal, and replicated prior reports of reduced dorsomedial prefrontal cortex activation with older age, with similar reductions in precuneus, right anterior insula/operculum, and a region extending from thalamus to striatum. We used independent component analysis to identify distinct anterior and posterior components of the default mode network (DMN), which were associated with the self-appraisal and rest-fixation parts of the task, respectively. Increasing age was associated with reduced functional connectivity between the two components. Finally, analyses of task-evoked interactions between pairs of nodes within the DMN identified a subnetwork that demonstrated reduced connectivity with increasing age. Decreased network integration within the DMN appears to be an important higher-order maturational process supporting the emerging adult self.
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ItemNo Preview AvailableFunctional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder(CMA-CANADIAN MEDICAL ASSOC, 2015-01)BACKGROUND: Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics. METHODS: Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls. RESULTS: We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders. LIMITATIONS: Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants. CONCLUSION: We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.
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ItemNo Preview AvailableAltered Striatal Functional Connectivity in Subjects With an At-Risk Mental State for Psychosis(OXFORD UNIV PRESS, 2014-07)Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.
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ItemNo Preview AvailableCompetitive and cooperative dynamics of large-scale brain functional networks supporting recollection(NATL ACAD SCIENCES, 2012-07-31)Analyses of functional interactions between large-scale brain networks have identified two broad systems that operate in apparent competition or antagonism with each other. One system, termed the default mode network (DMN), is thought to support internally oriented processing. The other system acts as a generic external attention system (EAS) and mediates attention to exogenous stimuli. Reports that the DMN and EAS show anticorrelated activity across a range of experimental paradigms suggest that competition between these systems supports adaptive behavior. Here, we used functional MRI to characterize functional interactions between the DMN and different EAS components during performance of a recollection task known to coactivate regions of both networks. Using methods to isolate task-related, context-dependent changes in functional connectivity between these systems, we show that increased cooperation between the DMN and a specific right-lateralized frontoparietal component of the EAS is associated with more rapid memory recollection. We also show that these cooperative dynamics are facilitated by a dynamic reconfiguration of the functional architecture of the DMN into core and transitional modules, with the latter serving to enhance integration with frontoparietal regions. In particular, the right posterior cingulate cortex may act as a critical information-processing hub that provokes these context-dependent reconfigurations from an intrinsic or default state of antagonism. Our findings highlight the dynamic, context-dependent nature of large-scale brain dynamics and shed light on their contribution to individual differences in behavior.
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ItemNo Preview AvailableBrain functional connectivity during induced sadness in patients with obsessive-compulsive disorder(CMA-CANADIAN MEDICAL ASSOC, 2012-07)BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation. METHODS: Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness. RESULTS: We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus. LIMITATIONS: Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis. CONCLUSION: The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized "OCD circuit," which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.