scholarly journals Astrocytes in the external globus pallidus coordinate flexibility of action strategy

2021 ◽  
Author(s):  
Sa-Ik Hong ◽  
Seungwoo Kang ◽  
Minryung Song ◽  
Minsu Yang ◽  
Matthew Baker ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Temporal Dynamics ◽  
Behavioral Flexibility ◽  
Support Vector ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Reward Seeking ◽  
Reward Delivery ◽  
Action Strategy ◽  
Directed Learning

Abstract The external globus pallidus (GPe) is an integrative hub and gateway for behavioral flexibility in reward-related behaviors. However, it remains unknown whether enriched astrocytes in the GPe guide behavioral flexibility. Here, we trained mice to exhibit goal-directed and habitual reward-seeking behaviors using the behavior tasks with effort- and time-based reward delivery, respectively. Then, we examined the temporal dynamics of GPe astrocytes during goal-directed and habitual learning. Overall, GPe astrocytes were substantially silenced during habitual learning compared to goal-directed learning. In the timescale of action events, GPe astrocyte activities were increased immediately after termination of reward-taking behavior before the following action. However, during habitual learning, the increase of astrocyte activity was not evident. Moreover, support vector machine (SVM) analysis demonstrated that GPe astrocytes dynamics predicted whether mice perform goal-directed or habitual behaviors. Interestingly, chemogenetic activation of GPe astrocytes, which dampened GPe neuronal firings and habitual behaviors, exhibting goal-directed behaviors. Strikingly, brief and repeated attentional stimulations recapitulated the effect of chemogenetic activation of GPe in intervening the habitual reward-seeking behaviors with increased GPe astrocyte activities. Our findings reveal a novel insight that increasing GPe astrocytic activities attenuates habitual behavior and improves behavioral flexibility, which may provide a potential therapeutic target for decision-making-related disorders, such as obsessive-compulsive disorder and addiction.

scholarly journals Stopping a Response When You Really Care about the Action: Considerations from a Clinical Perspective

2021 ◽  
Vol 11 (8) ◽  
pp. 979
Author(s):  
Sharon Morein-Zamir ◽  
Gideon Anholt
Keyword(s):  
Response Inhibition ◽  
Action Control ◽  
Common Denominator ◽  
Obsessive Compulsive ◽  
Apparent Paradox ◽  
Compulsive Disorder ◽  
Reward Seeking ◽  
Threat Avoidance ◽  
The Individual ◽  
Action Tendencies

Response inhibition, whether reactive or proactive, is mostly investigated in a narrow cognitive framework. We argue that it be viewed within a broader frame than the action being inhibited, i.e., in the context of emotion and motivation of the individual at large. This is particularly important in the clinical domain, where the motivational strength of an action can be driven by threat avoidance or reward seeking. The cognitive response inhibition literature has focused on stopping reactively with responses in anticipation of clearly delineated external signals, or proactively in limited contexts, largely independent of clinical phenomena. Moreover, the focus has often been on stopping efficiency and its correlates rather than on inhibition failures. Currently, the cognitive and clinical perspectives are incommensurable. A broader context may explain the apparent paradox where individuals with disorders characterised by maladaptive action control have difficulty inhibiting their actions only in specific circumstances. Using Obsessive Compulsive Disorder as a case study, clinical theorising has focused largely on compulsions as failures of inhibition in relation to specific internal or external triggers. We propose that the concept of action tendencies may constitute a useful common denominator bridging research into motor, emotional, motivational, and contextual aspects of action control failure. The success of action control may depend on the interaction between the strength of action tendencies, the ability to withhold urges, and contextual factors.

scholarly journals Behavioral flexibility in a mouse model for obsessive‐compulsive disorder: Impaired Pavlovian reversal learning in SAPAP3 mutants

2019 ◽  
Vol 18 (4) ◽  
pp. e12557 ◽  
Author(s):  
Bastijn J.G. van den Boom ◽  
Adriana H. Mooij ◽  
Ieva Misevičiūtė ◽  
Damiaan Denys ◽  
Ingo Willuhn
Keyword(s):  
Mouse Model ◽  
Obsessive Compulsive Disorder ◽  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Tractography-Guided Deep Brain Stimulation of the Anteromedial Globus Pallidus Internus for Refractory Obsessive-Compulsive Disorder: Case Report

Neurosurgery ◽  
2019 ◽  
Author(s):  
Amit Azriel ◽  
Sarah Farrand ◽  
Maria Di Biase ◽  
Andrew Zalesky ◽  
Elaine Lui ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Globus Pallidus ◽  
Brain Stimulation ◽  
Surgical Planning ◽  
Globus Pallidus Internus ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Treatment Refractory ◽  
Deep Brain

AbstractBACKGROUND AND IMPORTANCEObsessive-compulsive disorder (OCD) is a disabling psychiatric disorder, mainly treated with psychotherapy and pharmacotherapy. Surgical intervention may be appropriate for patients with treatment-refractory OCD. Deep brain stimulation (DBS) is an alternative for previously common ablative surgical procedures. Tractography has been proposed as a method for individualizing DBS treatment and may have the potential to improve efficacy.CLINICAL PRESENTATIONWe present a patient with treatment-refractory OCD previously treated with bilateral leucotomies, who underwent DBS surgery with targeting informed by tractography. Preoperative tractography to identify suitable DBS targets was undertaken. Structural images were also utilized for standard stereotactic surgical planning. The anteromedial globus pallidus internus (amGPi) was chosen as the target bilaterally after consideration of white matter projections to frontal cortical regions and neurosurgical approach. Bilateral amGPi DBS surgery was undertaken without adverse events. At 16-mo follow-up, there was a 48.5% reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale.CONCLUSIONThe amGPi can be a successful DBS target for OCD. This is the first known case to report on DBS surgery postleucotomies for OCD and highlights the utility of tractography for surgical planning in OCD.

scholarly journals Consider Role of Glutamatergic Habenula-projecting Globus Pallidus in OCD

2019 ◽  
Vol 52 (04) ◽  
pp. 203-204
Author(s):  
Anton J.M. Loonen ◽  
Svetlana A. Ivanova
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Globus Pallidus ◽  
Review Article ◽  
Specific Role ◽  
Future Research ◽  
Glutamatergic System ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Primary Relationship

AbstractRecently, in a review article in this journal, Vlček and colleagues described the putative role played by the glutamatergic system in obsessive-compulsive disorder (OCD) and how this might explain the effects of certain treatments. They describe a neuroanatomical model, which includes a specific role of the amygdala-hippocampus complex (AHC) and would complete the classic cortico-striatal-thalamo-cortical (CSTC) mechanism of OCD. The role of the AHC can perhaps be better understood when considering its ancient relationship to the rest of the forebrain of mammals. This leads to distinguishing between primary (lamprey-like), secondary (amphibian-like) and tertiary (mammal-like) parts of the forebrain including amygdaloid, ventral extrapyramidal and dorsal extrapyramidal systems, respectively. A specific role in OCD may be played by the habenula-projecting part of the pallidum, which evaluated the result of behaviour in human’s earliest vertebrate ancestors. The addition of these primary relationship to the authors’ description could be fruitful when planning the future research, as suggested by them.

scholarly journals Defining data-driven subgroups of obsessive–compulsive disorder with different treatment responses based on resting-state functional connectivity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Seoyeon Kwak ◽  
Minah Kim ◽  
Taekwan Kim ◽  
Yoobin Kwak ◽  
Sanghoon Oh ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Treatment Response ◽  
Obsessive Compulsive Disorder ◽  
Resting State ◽  
Predictive Biomarkers ◽  
Support Vector ◽  
Resting State Functional Connectivity ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Treatment Responses

Abstract Characterization of obsessive–compulsive disorder (OCD), like other psychiatric disorders, suffers from heterogeneities in its symptoms and therapeutic responses, and identification of more homogeneous subgroups may help to resolve the heterogeneity. We aimed to identify the OCD subgroups based on resting-state functional connectivity (rsFC) and to explore their differences in treatment responses via a multivariate approach. From the resting-state functional MRI data of 107 medication-free OCD patients and 110 healthy controls (HCs), we selected rsFC features, which discriminated OCD patients from HCs via support vector machine (SVM) analyses. With the selected brain features, we subdivided OCD patients into subgroups using hierarchical clustering analyses. We identified 35 rsFC features that achieved a high sensitivity (82.74%) and specificity (76.29%) in SVM analyses. The OCD patients were subdivided into two subgroups, which did not show significant differences in their demographic and clinical backgrounds. However, one of the OCD subgroups demonstrated more impaired rsFC that was involved either within the default mode network (DMN) or between DMN brain regions and other network regions. This subgroup also showed both lower improvements in symptom severity in the 16-week follow-up visit and lower responder percentage than the other subgroup. Our results highlight that not only abnormalities within the DMN but also aberrant rsFC between the DMN and other networks may contribute to the treatment response and support the importance of these neurobiological alterations in OCD patients. We suggest that abnormalities in these connectivity may play predictive biomarkers of treatment response, and aid to build more optimal treatment strategies.

Obsessive—compulsive disorder following bilateral globus pallidus infarction

1997 ◽  
Vol 42 (5) ◽  
pp. 410-412 ◽  
Author(s):  
P. Rodrigo Escalona ◽  
John C. Adair ◽  
Brian B. Roberts ◽  
David A. Graeber
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Globus Pallidus ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Task-Based Functional Neuroimaging Studies of Obsessive-Compulsive Disorder: A Hypothesis-Driven Review

2017 ◽  
Author(s):  
M. M Vaghi ◽  
T. W Robbins
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Functional Neuroimaging ◽  
Neural Substrates ◽  
Brain Regions ◽  
Cognitive Tasks ◽  
Functional Magnetic Resonance ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Directed Learning ◽  
Experimental Level

The neurobiological basis of Obsessive Compulsive Disorder (OCD) has been probed using functional magnetic resonance in hundreds of studies over three decades. This complex literature can be syntheized using a theory-informed approach. At a theoretical level, separable, independent, constructs of relevance to OCD have been identified. At the experimental level, extensive translational evidence has provided an account that relates specific brain systems to these neuropsychological constructs. Parallels between neural substrates implicated in OCD and functional specialization of different brain regions suggest that abnormalities within fronto-striatal circuitry impinge on executive functions, and their subcomponents, and on goal-directed learning and habit formation. In OCD, this is reflected at a functional level in patterns of abnormal activations in particular brain regions during specific cognitive tasks. However, many issues still need to be addressed. The authors suggest that the experimental context might represent a pivotal variable that should be taken into account.

Impairment in the goal-directed corticostriatal learning system as a biomarker for obsessive–compulsive disorder

2019 ◽  
Vol 50 (9) ◽  
pp. 1490-1500 ◽  
Author(s):  
Chenjie Dong ◽  
Qiong Yang ◽  
Jingjing Liang ◽  
Carol A. Seger ◽  
Hongying Han ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Obsessive Compulsive Disorder ◽  
Effective Connectivity ◽  
Learning System ◽  
Causality Analysis ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
First Degree Relatives ◽  
Left Caudate ◽  
Directed Learning

AbstractBackgroundCompulsive behaviors in obsessive-compulsive disorder (OCD) have been related to impairment within the associative cortical-striatal system connecting the caudate and prefrontal cortex that underlies consciously-controlled goal-directed learning and behavior. However, little is known whether this impairment may serve as a biomarker for vulnerability to OCD.MethodsUsing resting-state functional magnetic resonance imaging (fMRI), we employed Granger causality analysis (GCA) to measure effective connectivity (EC) in previously validated striatal sub-regions, including the caudate, putamen, and the nucleus accumbens, in 35 OCD patients, 35 unaffected first-degree relatives and 35 matched healthy controls.ResultsBoth OCD patients and their first-degree relatives showed greater EC than controls between the left caudate and the orbital frontal cortex (OFC). Both OCD patients and their first-degree relatives showed lower EC than controls between the left caudate and lateral prefrontal cortex. These results are consistent with findings from task-related fMRI studies which found impairment in the goal-directed system in OCD patients.ConclusionsThe same changes in EC were present in both OCD patients and their unaffected first-degree relatives suggest that impairment in the goal-directed learning system may be a biomarker for OCD.

Compulsivity and probabilistic reversal learning in OCD and cocaine addiction

2015 ◽  
Vol 30 (S2) ◽  
pp. S110-S111 ◽  
Author(s):  
P. Smith ◽  
N. Benzina ◽  
F. Vorspan ◽  
L. Mallet ◽  
K. N’Diaye
Keyword(s):  
Reversal Learning ◽  
A Priori ◽  
Behavioral Flexibility ◽  
Learning Task ◽  
Repetitive Behaviors ◽  
Cocaine Addiction ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Cocaine Users ◽  
Probabilistic Reversal Learning

Compulsive behavior is a core symptom of both obsessive compulsive disorder (OCD) and cocaine addiction (CA). Across both pathologies, one can identify a priori goal-directed actions (purportedly anxiolytic checking or washing in OCD and pleasure-seeking drug use in addiction) that turn into rigid, ritualized and repetitive behaviors over which the patient loose control. One possible psychopathological mechanism underlying compulsivity is behavioral inflexibility, namely a deficit in the aptitude to dynamically adapt to novel contexts and changing reward rules. The probabilistic reversal learning paradigm allows to objectively assess behavioral flexibility by challenging participants with a task where they have to learn through trials-and-errors which of two stimuli is the most-often rewarded one, while adjusting to sudden inconspicuous contingency reversals. We therefore hypothesized that both OCD and CA would be associated with impaired cognitive flexibility, as measured through perseverative response rate following contingency reversals in this task. Interestingly, impulsivity may also be assessed within this task via the tendency of participants to switch from one stimulus to the other following probabilistic errors. To investigate cognitive inflexibility in relation to CA and OCD respectively, we first compared the performance in a probabilistic reversal learning task of cocaine users, ex cocaine users (abstinent for 2 months or more), and controls, as well as that of participants from the general population whose obsessive-compulsive traits were assessed using the OCI-R, a well-validated self-questionnaire. Our task yielded results similar to those found in the literature: cocaine addicts changed their responses more often, and learned less effectively. Ex-cocaine addicts performed better than addicts but worse than controls, suggesting that addicts’ poor results may be in part explained by reversible cognitive consequences of addiction. Addicts with less cognitive impairments may also be less likely to relapse. Regarding the relationship of flexibility to subclinical OCD traits, we found no link between OCI-R score and perseveration, or between impulsiveness and excessive switching.

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