Faculty Bibliography
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98
Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups
OBJECTIVE:Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS:-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS:No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS:The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
PMID: 32539527
ISSN: 1535-7228
CID: 4484542
Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium
BACKGROUND:Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS:We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS:In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS:The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
PMID: 31178097
ISSN: 1873-2402
CID: 3929742
Ketamine normalizes subgenual cingulate cortex hyper-activity in depression
Mounting evidence supports the rapid antidepressant efficacy of the N-methyl-D-aspartate receptor antagonist, ketamine, for treating major depressive disorder (MDD); however, its neural mechanism of action remains poorly understood. Subgenual anterior cingulate cortex (sgACC) hyper-activity during rest has been consistently implicated in the pathophysiology of MDD, potentially driven in part by excessive hippocampal gluatmatergic efferents to sgACC. Reduction of sgACC activity has been associated with successful antidepressant treatment. This study aimed to examine whether task-based sgACC activity was higher in patients with MDD compared to controls and to determine whether this activity was altered by single-dose ketamine. In Study 1, patients with MDD (N = 28) and healthy controls (N = 20) completed task-based functional magnetic resonance imaging using an established incentive-processing task. In Study 2, a second cohort of patients with MDD (N = 14) completed the same scanning protocol at baseline and following a 40 min infusion of ketamine (0.5 mg/kg). Task-based activation of sgACC was examined with a seed-driven analysis assessing group differences and changes from pre to post treatment. Patients with MDD showed higher sgACC activation to positive and negative monetary incentives compared to controls, associated with anhedonia and anxiety, respectively. In addition, patients with MDD had higher resting-state functional connectivity between hippocampus and sgACC, associated with sgACC hyper-activation to positive incentives, but not negative incentives. Finally, ketamine reduced sgACC hyper-activation to positive incentives, but not negative incentives. These findings suggest a neural mechanism by which ketamine exerts its antidepressant efficacy, via rapid blunting of aberrant sgACC hyper-reactivity to positive incentives.
PMID: 31896116
ISSN: 1740-634x
CID: 4297772
The buildup of an urge in obsessive-compulsive disorder: Behavioral and neuroimaging correlates
Obsessive-compulsive disorder (OCD) is highly heterogeneous. While obsessions often involve fear of harm, many patients report uncomfortable sensations and/or urges that drive repetitive behaviors in the absence of a specific fear. Prior work suggests that urges in OCD may be similar to everyday "urges-for-action" (UFA) such as the urge to blink, swallow, or scratch, but very little work has investigated the pathophysiology underlying urges in OCD. In the current study, we used an urge-to-blink approach to model sensory-based urges that could be experimentally elicited and compared across patients and controls using the same task stimuli. OCD patients and controls suppressed eye blinking over a period of 60 s, alternating with free blinking blocks, while brain activity was measured using functional magnetic resonance imaging. OCD patients showed significantly increased activation in several regions during the early phase of eyeblink suppression (first 30 s), including mid-cingulate, insula, striatum, parietal cortex, and occipital cortex, with lingering group differences in parietal and occipital regions during late eyeblink suppression (last 30 s). There were no differences in brain activation during free blinking blocks, and no conditions where OCD patients showed reduced activation compared to controls. In an exploratory analysis of blink counts performed in a subset of subjects, OCD patients were less successful than controls in suppressing blinks. These data indicate that OCD patients exhibit altered brain function and behavior when experiencing and suppressing the urge to blink, raising the possibility that the disorder is associated with a general abnormality in the UFA system that could ultimately be targeted by future treatments.
PMID: 31916668
ISSN: 1097-0193
CID: 4257542
Anticipatory feelings: neural correlates and linguistic markers
This review introduces anticipatory feelings (AF) as a new construct related to the process of anticipation and prediction of future events. AF, defined as the state of awareness of physiological and neurocognitive changes that occur within an oganism in the form of a process of adapting to future events, are an important component of anticipation and expectancy. They encompass bodily-related interoceptive and affective components and are influenced by intrapersonal and dispositional factors, such as optimism, hope, pessimism, or worry. In the present review, we consider evidence from animal and human research, including neuroimaging studies, to characterize the brain structures and brain networks involved in AF. The majority of studies reviewed revealed three brain regions involved in future oriented feelings: 1) the insula; 2) the ventromedial prefrontal cortex (vmPFC); and 3) the amygdala. Moreover, these brain regions were confirmed by a meta-analysis, using a platform for large-scale, automated synthesis of fMRI data. Finally, by adopting a neurolinguistic and a big data approach, we illustrate how AF are expressed in language.
PMID: 32061891
ISSN: 1873-7528
CID: 4313052
Imaging of obsessive-compulsive disorder
New York, NY : Oxford University Press, [2020]
pp. -
ISBN: 9780198713005
CID: 5545662
Identifying Subtypes of Sensory Symptoms in Obsessive-Compulsive Disorder [Meeting Abstract]
ISI:000535308201226
ISSN: 0006-3223
CID: 4560912
Positive Valence Systems Deficits in Adolescent Depression [Meeting Abstract]
ISI:000535308201030
ISSN: 0006-3223
CID: 4560882
Resting-State Functional Connectivity Underlying Interoception in Obsessive-Compulsive Disorder [Meeting Abstract]
ISI:000535308201318
ISSN: 0006-3223
CID: 4560962
Relationships between neural activation during a reward task and peripheral cytokine levels in youth with diverse psychiatric symptoms
BACKGROUND:Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. METHODS:Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). RESULTS:Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-β) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. CONCLUSIONS:Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.
PMCID:6660409
PMID: 30953769
ISSN: 1090-2139
CID: 4021922
