scholarly journals Dopamine Signaling in the Dorsomedial Striatum Promotes Compulsive Behavior

2020 ◽  
Author(s):  
Jillian L. Seiler ◽  
Caitlin V. Cosme ◽  
Venus N. Sherathiya ◽  
Joseph M. Bianco ◽  
Talia N. Lerner
Keyword(s):  
Reinforcement Learning ◽  
Neural Activity ◽  
Compulsive Behavior ◽  
Experimental Paradigm ◽  
Random Interval ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Dopamine Signaling ◽  
Dopamine Signal ◽  
Dorsomedial Striatum

SUMMARYHabits and compulsions are two aspects of behavior that often develop in parallel and together lead to inflexible responding. Both habits and compulsions are hypothesized to be involved in psychiatric disorders such as drug addiction and obsessive-compulsive disorder (OCD), but they are distinct behaviors that may rely on different brain circuitries. We developed an experimental paradigm to track the development of both habits and compulsions in individual animals while recording neural activity. We performed fiber photometry measurements of dopamine axon activity while mice engaged in reinforcement learning on a random interval (RI60) schedule and found that the emergence of compulsion was predicted by the dopamine signal in the dorsomedial striatum (DMS). By amplifying this DMS dopamine signal throughout training using optogenetics, we accelerated animals’ transitions to compulsion, irrespective of habit formation. These results establish DMS dopamine signaling as a key controller of compulsions.

scholarly journals Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Sanghoon Oh ◽  
Wi Hoon Jung ◽  
Taekwan Kim ◽  
Geumsook Shim ◽  
Jun Soo Kwon
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cognitive Function ◽  
Neural Activity ◽  
Symptom Severity ◽  
Brain Activation ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
The Relationship

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive–Compulsive Disorder

2019 ◽  
Vol 29 (11) ◽  
pp. 4753-4762 ◽  
Author(s):  
Jesus Pujol ◽  
Laura Blanco-Hinojo ◽  
Dídac Maciá ◽  
Pino Alonso ◽  
Ben J Harrison ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Obsessive Compulsive Disorder ◽  
Neural Activity ◽  
Orbitofrontal Cortex ◽  
Inhibitory Neuron ◽  
Functional Structure ◽  
Neuron Activity ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Neurophysiological Studies

AbstractWe mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive–compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.

Effect of amphetamine on behavioral patterns of obsessive-compulsive and addictive gambling in a rat marble test

2016 ◽  
Vol 14 (3) ◽  
pp. 46-52 ◽  
Author(s):  
Petr D. Shabanov ◽  
Andrei A. Lebedev ◽  
Natalia D. Yakushina ◽  
Anna G. Pshenichnaya ◽  
Eugenii R. Bychkov
Keyword(s):  
Pathological Gambling ◽  
Field Evaluation ◽  
Anxiety Reduction ◽  
Dependent Manner ◽  
Behavioral Patterns ◽  
Compulsive Behavior ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Dose Dependent ◽  
The Brain

A rodent marble test can be qualified as the most informative test of evaluation of obsessive-compulsive disorder as a neurobiological component of pathological gambling. Several behavioral components of obsession (obsessive and anxious ideas) and compulsions (obsessive actions) directed to anxiety reduction are modeled in this test. The effect of psychostimulant amphetamine on the rat behavior was studied in a marble test, anxiety-phobic model (scale), open field (evaluation of motor and emotional activity) and resident-intruder test (Intraspecies behavior). Amphetamine 0.5 and 1.5 mg/kg increased a number of burying bolls and elevated anxiety level in dose dependent manner. This accompanied with reduction of explorative activity, elevation of motor activity and number of individual behavioral patterns. Therefore, dopaminergic system of the brain activated with amphetamine is involved in obsessive-compulsive behavior and pathological gambling.

Psychostimulant-Induced Behavior as an Animal Model of Obsessive-Compulsive Disorder: An Ethological Approach to the Form of Compulsive Rituals

CNS Spectrums ◽  
2005 ◽  
Vol 10 (3) ◽  
pp. 191-202 ◽  
Author(s):  
David Eilam ◽  
Henry Szechtman
Keyword(s):  
Animal Model ◽  
Obsessive Compulsive Disorder ◽  
Rat Model ◽  
Receptor Agonist ◽  
Dopamine Receptor Agonist ◽  
Compulsive Behavior ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Dopaminergic Mechanisms ◽  
Motor Acts

AbstractRats treated chronically with the D2/D3, dopamine receptor agonist quinpirole show a pattern of behavior that meets a set of ethologically derived criteria of compulsive behavior in obsessive-compulsive disorder (OCD). Moreover, in both quinpirole-treated rats and OCD patients, the structure of compulsive rituals appear similar in being composed of relatively few motor acts that are organized in a flexible yet recurrent manner. In addition, the development of compulsive behavior in quinpirole-treated rats is attenuated by the OCD pharmacotherapeutic drug clomipramine. These similarities support the validity of quinpirole-treated rats as a psychostimulant-induced animal model of OCD. Considering that the induction of compulsive behavior in the rat model involves chronic hyperstimulation of dopamine receptors, this raises the possibility that dopaminergic mechanisms may play a role in OCD, at least in some subtypes of this disorder.

scholarly journals Characterizing a psychiatric symptom dimension related to deficits in goal-directed control

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Claire M Gillan ◽  
Michal Kosinski ◽  
Robert Whelan ◽  
Elizabeth A Phelps ◽  
Nathaniel D Daw
Keyword(s):  
Large Scale ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
Compulsive Behavior ◽  
Neurocognitive Performance ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Diagnostic Categories ◽  
Symptom Dimension ◽  
Compulsive Behaviors

Prominent theories suggest that compulsive behaviors, characteristic of obsessive-compulsive disorder and addiction, are driven by shared deficits in goal-directed control, which confers vulnerability for developing rigid habits. However, recent studies have shown that deficient goal-directed control accompanies several disorders, including those without an obvious compulsive element. Reasoning that this lack of clinical specificity might reflect broader issues with psychiatric diagnostic categories, we investigated whether a dimensional approach would better delineate the clinical manifestations of goal-directed deficits. Using large-scale online assessment of psychiatric symptoms and neurocognitive performance in two independent general-population samples, we found that deficits in goal-directed control were most strongly associated with a symptom dimension comprising compulsive behavior and intrusive thought. This association was highly specific when compared to other non-compulsive aspects of psychopathology. These data showcase a powerful new methodology and highlight the potential of a dimensional, biologically-grounded approach to psychiatry research.

Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder

CNS Spectrums ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 295-304 ◽  
Author(s):  
Gabriela M. Ferreira ◽  
Murat Yücel ◽  
Andrew Dawson ◽  
Valentina Lorenzetti ◽  
Leonardo F. Fontenelle
Keyword(s):  
Positive Affect ◽  
Obsessive Compulsive Disorder ◽  
Impulse Control ◽  
Habit Strength ◽  
Self Report ◽  
Compulsive Behavior ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Duration Of Illness ◽  
Compulsive Behaviors

AimsTo determine the rates and associated illness characteristics of obsessive-compulsive disorder (OCD) patients who describe their symptoms as either rewarding or habitual.MethodsSeventy-three treatment-seeking OCD patients had their dominant compulsive behavior assessed with a structured interview (the Temporal Impulsive-Compulsive Scale–Revised) to track the progression of rewarding (ie, gain in positive affect), aversive (ie, decrease in negative affect), and neutral (or non-affective) states and a self-report scale (the Self-Report Habit Index) to evaluate their habitual features. Additional measures included structured diagnostic interviews for axis I and II disorders, measures of OCD symptoms severity, and a battery of instruments to comprehensively assess relevant aspects of sensitivity to reward and fear.ResultsAlmost half (49%) of our OCD patients (particularly washers) endorsed that they anticipated obtaining a reward (ie, positive affect) from the enactment of their dominant compulsive behavior. Washers stood out in that their positive affects during and after compulsive behaviors were highly (and positively) correlated with duration of illness. In contrast, habit strength did not differ between washers, checkers, and arrangers, although it also correlated with duration of illness among checkers. Furthermore, the severity of OCD and comorbidity with impulse control disorders predicted up to 35% of the variance in the habit strength of OCD behaviors.ConclusionCompulsive washing may be more clearly characterized by problems in reward processing. In contrast, duration of checking, severity of OCD, and comorbidity with impulse control disorders shape compulsive behaviors by imparting them with habitual tendencies.

scholarly journals Transdiagnostic phenotypes of compulsive behavior and associations with psychological, cognitive, and neurobiological affective processing

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Lauren Den Ouden ◽  
Chao Suo ◽  
Lucy Albertella ◽  
Lisa-Marie Greenwood ◽  
Rico S. C. Lee ◽  
...  
Keyword(s):  
Statistical Modeling ◽  
Biological Assessment ◽  
Affective Processing ◽  
Phenotypic Variance ◽  
Compulsive Behavior ◽  
Resting State Functional Connectivity ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Diagnostic Categories ◽  
The Stability

AbstractCompulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous sample of community-based individuals (N = 45; 18–45 years; 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger samples are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.

scholarly journals Parallel valence processing alterations associated with compulsive behavior in SAPAP3 knockout mice and human OCD

2021 ◽  
Author(s):  
Bridget L. Kajs ◽  
Peter J. van Roessel ◽  
Gwynne L. Davis ◽  
Leanne M. Williams ◽  
Carolyn I. Rodriguez ◽  
...  
Keyword(s):  
Emotional Valence ◽  
Rodent Model ◽  
Therapeutic Interventions ◽  
Rodent Models ◽  
Compulsive Behavior ◽  
Obsessive Compulsive ◽  
Implicit Processing ◽  
Compulsive Disorder ◽  
Negative Valence ◽  
Positive Valence

Abnormalities in valence processing - the processing of aversive or appetitive stimuli - may be an underrecognized component of obsessive-compulsive disorder (OCD). Independent experimental paradigms have suggested disturbance of emotional valence systems in OCD, yet no standardized assay has been employed to assess both negative and positive valence processing in clinical studies of OCD patients, either at baseline or in response to therapeutic interventions. Additionally, preclinical rodent models are critical for treatment discovery in OCD, yet investigations examining whether rodent models of compulsive behavior similarly show alterations in valence systems have been limited. We sought to establish paradigms for assessing valence processing across both human OCD patients and in a preclinical rodent model: in OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence); in the SAPAP3 knockout (KO) mouse model of compulsive behavior, we used auditory fear conditioning and extinction (negative valence) and reward-based operant conditioning (positive valence). We find that OCD patients show enhanced negative and impaired positive valence processing, and that performance on valence processing tasks correlates with clinical measures of OCD severity. We further find that SAPAP3 KO mice show heightened negative and impaired positive valence processing alterations similar to those of OCD patients. Our results show parallel valence processing abnormalities in OCD patients and a preclinical rodent model of compulsive behavior, and suggest valence processing alterations as novel therapeutic targets across a translational research spectrum.

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