Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder.
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ABSTRACT:
SUBMITTER: Vaghi MM
PROVIDER: S-EPMC5684958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity.MethodsMultiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived.ResultsReduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects.ConclusionsThese data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.
| S-EPMC6020061 | biostudies-literature
Project description:ImportanceDimensional definitions of transdiagnostic mental health problems have been suggested as an alternative to categorical diagnoses, having the advantage of capturing heterogeneity within diagnostic categories and similarity across them and bridging more naturally psychological and neural substrates.ObjectiveTo examine whether a self-reported compulsivity dimension has a stronger association with goal-directed and related higher-order cognitive deficits compared with a diagnosis of obsessive-compulsive disorder (OCD).Design, setting, and participantsIn this cross-sectional study, patients with OCD and/or generalized anxiety disorder (GAD) from across the United States completed a telephone-based diagnostic interview by a trained rater, internet-based cognitive testing, and self-reported clinical assessments from October 8, 2015, to October 1, 2017. Follow-up data were collected to test for replicability.Main outcomes and measuresPerformance was measured on a test of goal-directed planning and cognitive flexibility (Wisconsin Card Sorting Test [WCST]) and a test of abstract reasoning. Clinical variables included DSM-5 diagnosis of OCD and GAD and 3 psychiatric symptom dimensions (general distress, compulsivity, and obsessionality) derived from a factor analysis.ResultsOf 285 individuals in the analysis (mean [SD] age, 32 [12] years; age range, 18-77 years; 219 [76.8%] female), 111 had OCD; 82, GAD; and 92, OCD and GAD. A diagnosis of OCD was not associated with goal-directed performance compared with GAD at baseline (? [SE], -0.02 [0.02]; P?=?.18). In contrast, a compulsivity dimension was negatively associated with goal-directed performance (? [SE], -0.05 [0.02]; P?=?.003). Results for abstract reasoning task and WCST mirrored this pattern; the compulsivity dimension was associated with abstract reasoning (? [SE], 2.99 [0.63]; P?<?.001) and several indicators of WCST performance (eg, categories completed: ? [SE], -0.57 [0.09]; P?<?.001), whereas OCD diagnosis was not (abstract reasoning: ? [SE], 0.39 [0.66]; P?=?.56; categories completed: ? [SE], -0.09 [0.10]; P?=?.38). Other symptom dimensions relevant to OCD, obsessionality, and general distress had no reliable association with goal-directed performance, WCST, or abstract reasoning. Obsessionality had a positive association with requiring more trials to reach the first category on the WCST at baseline (? [SE], 2.92 [1.39]; P?=?.04), and general distress was associated with impaired goal-directed performance at baseline (? [SE],-0.04 [0.02]; P?=?.01). However, unlike the key results of this study, neither survived correction for multiple comparisons or was replicated at follow-up testing.Conclusions and relevanceDeficits in goal-directed planning in OCD may be more strongly associated with a compulsivity dimension than with OCD diagnosis. This result may have implications for research assessing the association between brain mechanisms and clinical manifestations and for understanding the structure of mental illness.
| S-EPMC6802255 | biostudies-literature
Project description:Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) while performing the ToL task at baseline and again after 16 weeks of SSRI treatment. Internetwork connectivity was compared across the groups and treatment statuses (pretreatment versus posttreatment). At baseline, compared with the HCs, the OCD patients showed lower internetwork connectivity between the dorsal attention network and the default-mode network during the ToL planning task. After 16 weeks of SSRI treatment, the OCD patients showed improved clinical symptoms accompanied by normalized network connectivity, although their improved behavioral performance in the ToL task did not reach that of the HCs. Our findings support the conceptualization of OCD as a network disease characterized by an imbalance between brain networks during goal-directed planning and suggest that internetwork connectivity may serve as an early biomarker of the effects of SSRIs on goal-directed planning.
| S-EPMC7691328 | biostudies-literature
Project description:BackgroundYouths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study.MethodsA total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control.ResultsAdolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control.ConclusionsThis study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.
| S-EPMC6088771 | biostudies-literature
Project description:Endophentoypes, quantifiable traits lying on the causal chain between a clinical phenotype and etiology, can be used to accelerate genomic discovery in obsessive-compulsive disorder (OCD). Here we identify the neuroanatomic changes that are shared by 22 OCD adult and adolescent patients and 25 of their unaffected siblings who are at genetic risk for the disorder. Comparisons were made against 47 age and sex matched healthy controls. We defined the surface morphology of the striatum, globus pallidus and thalamus, and thickness of the cerebral cortex. Patients with OCD show significant surface expansion compared with healthy controls, following adjustment for multiple comparisons, in interconnected regions of the caudate, thalamus and right orbitofrontal cortex. Their unaffected siblings show similar, significant expansion, most marked in the ventromedial caudate bilaterally, the right pulvinar thalamic nucleus and the right orbitofrontal cortex. These regions define a network that has been consistently implicated in OCD. In addition, both patients with OCD and unaffected siblings showed similar increased thickness of the right precuneus, which receives rich input from the thalamic pulvinar nuclei and the left medial temporal cortex. Anatomic change within the orbitofrontostriatal and posterior brain circuitry thus emerges as a promising endophenotype for OCD.
| S-EPMC5912882 | biostudies-literature
Project description:The classical cognitive-behavioral theory of obsessive-compulsive disorder (OCD) holds that compulsions are performed to reduce distress that is evoked by obsessions, whereas a recent neuroscience-inspired theory suggests that compulsivity results from a disbalance between goal-directed and habit-related neural networks. To bridge these theories, we investigated whether the balance between goal-directed and habit networks in patients with OCD was affected during psychological distress. Twenty-three OCD patients and twenty-three healthy controls participated in a controlled stress induction paradigm using the socially evaluated cold-pressor test in a crossover design. Stress responses were evaluated through cortisol levels, blood pressure, and anxiety ratings. Functional connectivity of the caudate nucleus and posterior putamen was assessed using seed region analysis of resting-state functional magnetic resonance imaging data, which are hubs of the goal-directed and habit network, respectively. Stress induction increased blood pressure and psychological stress measures across groups and resulted in blunted cortisol responses in patients. Furthermore, patients showed a blunted reduction in connectivity between the caudate nucleus and precuneus during psychological distress, which was positively correlated with compulsivity but not obsession severity. The posterior putamen showed no significant group differences in distress-induced connectivity. These results suggest that compulsivity in OCD is associated with altered connectivity between the goal-directed and default mode networks during psychological distress.
| S-EPMC7039895 | biostudies-literature
Project description:The aim of the current paper is to provide the first comparison of computational mechanisms and neurofunctional substrates in adolescents with attention-deficit/hyperactivity disorder (ADHD) and adolescents with obsessive-compulsive disorder (OCD) during decision making under ambiguity.Sixteen boys with ADHD, 20 boys with OCD, and 20 matched control subjects (12-18 years of age) completed a functional magnetic resonance imaging version of the Iowa Gambling Task. Brain activation was compared between groups using three-way analysis of covariance. Hierarchical Bayesian analysis was used to compare computational modeling parameters between groups.Patient groups shared reduced choice consistency and relied less on reinforcement learning during decision making relative to control subjects, while adolescents with ADHD alone demonstrated increased reward sensitivity. During advantageous choices, both disorders shared underactivation in ventral striatum, while OCD patients showed disorder-specific underactivation in the ventromedial orbitofrontal cortex. During outcome evaluation, shared underactivation to losses in patients relative to control subjects was found in the medial prefrontal cortex and shared underactivation to wins was found in the left putamen/caudate. ADHD boys showed disorder-specific dysfunction in the right putamen/caudate, which was activated more to losses in patients with ADHD but more to wins in control subjects.The findings suggest shared deficits in using learned reward expectancies to guide decision making, as well as shared dysfunction in medio-fronto-striato-limbic brain regions. However, findings of unique dysfunction in the ventromedial orbitofrontal cortex in OCD and in the right putamen in ADHD indicate additional, disorder-specific abnormalities and extend similar findings from inhibitory control tasks in the disorders to the domain of decision making under ambiguity.
| S-EPMC6278892 | biostudies-other
Project description:Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.
| S-EPMC5068758 | biostudies-literature
Project description:BackgroundObsessive-compulsive disorder (OCD) is a disorder of automatic, uncontrollable behaviors and obsessive rumination. There is evidence that OCD patients have difficulties performing goal-directed actions, instead exhibiting repetitive stimulus-response habit behaviors. This might result from the excessive formation of stimulus-response habit associations or from an impairment in the ability to use outcome value to guide behavior. We investigated the latter by examining counterfactual decision making, which is the ability to use comparisons of prospective action-outcome scenarios to guide economic choice.MethodsWe tested decision making (forward counterfactual) and affective responses (backward counterfactual) in 20 OCD patients and 20 matched healthy control subjects using an economic choice paradigm that previously revealed attenuation of both the experience and avoidance of counterfactual emotion in schizophrenia patients and patients with orbitofrontal cortex lesions.ResultsThe use of counterfactual comparison to guide decision making was diminished in OCD patients, who relied primarily on expected value. Unlike the apathetic affective responses previously shown to accompany this decision style, OCD patients reported increased emotional responsivity to the outcomes of their choices and to the counterfactual comparisons that typify regret and relief.ConclusionsObsessive-compulsive disorder patients exhibit a pattern of decision making consistent with a disruption in goal-directed forward modeling, basing decisions instead on the temporally present (and more rational) calculation of expected value. In contrast to this style of decision making, emotional responses in OCD were more extreme and reactive than control subjects. These results are in line with an account of disrupted goal-directed cognitive control in OCD.
| S-EPMC3988843 | biostudies-literature
Project description:Doubt is subjective uncertainty about one's perceptions and recall. It can impair decision-making and is a prominent feature of obsessive-compulsive disorder (OCD). We propose that evaluation of doubt during decision-making provides a useful endophenotype with which to study the underlying pathophysiology of OCD and potentially other psychopathologies. For the current study, we developed a new instrument, the Doubt Questionnaire, to clinically assess doubt. The random dot motion task was used to measure reaction time and subjective certainty, at varying levels of perceptual difficulty, in individuals who scored high and low on doubt, and in individuals with and without OCD. We found that doubt scores were significantly higher in OCD cases than controls. Drift diffusion modeling revealed that high doubt scores predicted slower evidence accumulation than did low doubt scores; and OCD diagnosis lower than controls. At higher levels of dot coherence, OCD participants exhibited significantly slower drift rates than did controls (q<0.05 for 30%, and 45% coherence; q<0.01 for 70% coherence). In addition, at higher levels of coherence, high doubt subjects exhibited even slower drift rates and reaction times than low doubt subjects (q<0.01 for 70% coherence). Moreover, under high coherence conditions, individuals with high doubt scores reported lower certainty in their decisions than did those with low doubt scores. We conclude that the Doubt Questionnaire is a useful instrument for measuring doubt. Compared to those with low doubt, those with high doubt accumulate evidence more slowly and report lower certainty when making decisions under conditions of low uncertainty. High doubt may affect the decision-making process in individuals with OCD. The dimensional doubt measure is a useful endophenotype for OCD research and could enable computationally rigorous and neurally valid understanding of decision-making and its pathological expression in OCD and other disorders.
| S-EPMC6564001 | biostudies-literature