Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways

doi:10.1016/j.tics.2011.11.003

Trends in Cognitive Sciences

Volume 16, Issue 1, January 2012, Pages 43-51

https://doi.org/10.1016/j.tics.2011.11.003 Get rights and content

Obsessive-compulsive disorder (OCD) affects approximately 2–3% of the population and is characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), typically performed in response to obsessions or related anxiety. In the past few decades, the prevailing models of OCD pathophysiology have focused on cortico-striatal circuitry. More recent neuroimaging evidence, however, points to critical involvement of the lateral and medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo-cortical circuitry, in addition to cortico-striatal circuitry, in the pathophysiology of the disorder. In this review, we elaborate proposed features of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and argue that this evidence suggests that fear extinction, in addition to behavioral inhibition, is impaired in OCD.

Section snippets

The current model of OCD

Intrusive thoughts, doubts, or concerns about safety, cleanliness, sex, violence, or symmetry, and urges to count or check ‘to be sure’ are common thoughts, feelings and behaviors that represent universal human experience to one degree or another. Healthy adaptive human function requires an ability to regulate and inhibit such intrusive thoughts, urges, feelings and behaviors. People with OCD are unable to control their thoughts and feelings and, consequently, experience obsessions accompanied

Why is the CSTC model insufficient?

Early characterizations of CSTC loops emphasized their parallel and segregated nature, emanating from various frontal subterritories and ramifying in specific striatal subterritories. For instance, one heuristic, dubbed ‘the striatal topography model of OCD and related disorders’, posited that comparable striatal pathology could explain the relationship between OCD and Tourette syndrome (TS); whereby OCD was the result of pathology within the caudate, disrupting OFC/ACC-caudate function,

The mOFC and lOFC

An extensive meta-analysis of OFC function associates the lOFC with processing negative valence and the mOFC with processing positive valence [24]. More specifically, the lOFC appears critical in responding to punishment and escape from danger, and may be involved in ritualized behavioral responses 25, 26, 27. The mOFC, by contrast, appears more involved in emotion regulation and reward processing. Extensive research conducted in rodents and healthy humans now implicates the ventromedial

The ACC: error processing and fear expression

The dACC is involved in numerous cognitive and affective functions, and is particularly relevant to OCD psychopathology. This brain region is involved in detecting the presence of cognitive conflict, and error monitoring and detection 44, 45. Common paradigms used to test the function of the dACC use an element of interference such that there are two conditions: congruent versus incongruent. Response to the congruent condition represents a prepotent or automatic response that is easy to

The amygdala and OCD

Although the amygdala responds to novelty, salience and a variety of emotional stimuli, its role in mediating fear and anxiety is the most commonly referenced [61]. In fact, the amygdala is often referred to as the hub of fear. A variety of experimental designs have been employed to test the role of the amygdala in fear and anxiety; these include the presentation of emotional faces, international affective picture system (IAPS) stimuli and classical fear conditioning. Such paradigms have

What is next in OCD research?

The past decade has witnessed expansive growth in neuroimaging and cognitive-behavioral neuroscience. Below, we highlight two prospective areas of research that may be ripe for additional advancements in knowledge regarding the neural basis of OCD and in the development of novel therapeutic approaches.

Concluding remarks

The cortico-striatal circuitry model of OCD pathophysiology emerged during the latter part of the 20th century and, for the past 25 years, has provided the principal platform for hypothesis-driven research in the field. Advances in neuroscience and progress in neuroimaging methods provided the means for extending and refining the original model. Specifically, (i) cortico-striatal loops are now understood to be interconnected rather than fully segregated, and OCD and related disorders may not

Disclosure Statement

S.L.R. has participated in research funded by Cyberonics and Medtronic. M.R.M. has received consulting fees from MircoTransponder Inc.

Acknowledgments

M.R.M. is supported by NIH grants R01-MH081975, DoD grant W81XWH-11-2-0079 and the Judah Foundation. We would like to thank Katelyn Trecartin and Daria Boratyn for their efforts in generating the figures and their assistance in conducting the meta-analysis.

Glossary

Cognitive behavioral therapy (CBT): a type of psychotherapy commonly utilized for the treatment of anxiety and mood disorders. The general focus of this therapy is to aid patients in restructuring their thinking patterns, to reduce unhelpful and/or unrealistic thoughts using cognitive (i.e. reappraisal) approaches and to modify behavioral responses, such as through graded exposure to fear-provoking stimuli and situations.
Deep brain stimulation (DBS): an intervention currently used for treatment of

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Advances in DTI studies for diagnoses and treatment of obsessive-compulsive disorder
2024, Psychiatry Research - Neuroimaging
This review summarizes the current state of neuroimaging research on obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI), which allows for the examination of white matter abnormalities in the brain. DTI studies on individuals with obsessive-compulsive disorder (OCD) consistently demonstrate widespread reductions in white matter integrity in various regions of the brain, including the corpus callosum, anterior and posterior cingulate cortex, and prefrontal cortex, which are involved in emotion regulation, decision-making, and cognitive control. However, the reviewed studies often have small sample sizes, and findings vary between studies, highlighting the need for larger and more standardized studies. Furthermore, discerning between causal and consequential effects of OCD on white matter integrity poses a challenge. Addressing this issue may be facilitated through longitudinal studies, including those evaluating the impact of treatment interventions, to enhance the accuracy of DTI data acquisition and processing, thereby improving the validity and comparability of study outcomes. In summary, DTI studies provide valuable insights into the neural circuits and connectivity disruptions in OCD, and future studies may benefit from standardized data analysis and larger sample sizes to determine whether structural abnormalities could be potential biomarkers for early identification and treatment of OCD.
Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up
2024, Psychiatry Research
Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy.
We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients.
Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively.
These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.
Associations between somatomotor-putamen resting state connectivity and obsessive-compulsive symptoms vary as a function of stress during early adolescence: Data from the ABCD study
2024, Brain Research Bulletin
Obsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9–12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (β = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.
Reduced sleep quality defines a subtype of obsessive-compulsive disorder with lower Glx levels in the resting thalamus and worse response inhibition
2024, Journal of Psychiatric Research
The aim of this study was to investigate the differences between resting and active thalamic neurometabolite levels and inhibitory function in obsessive compulsive disorder (OCD) patients with poor sleep quality (PSQ was defined as Pittsburgh Sleep Quality Index >5 and sleep efficiency ≤85%) compared to OCD patients with good sleep quality (GSQ) and healthy controls (HCs), as well as the relationship of these indices to obsessive compulsive symptoms.
Functional magnetic resonance spectroscopy (fMRS) was used to measure resting and active thalamic neurometabolite levels in 72 subjects (20 HCs and 38 OCD patients included in study analysis). Response inhibition function was measured by the Go-Nogo task before and during MRS recording. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The symptoms of OCD, anxiety and depression were evaluated using relevant clinical scales.
OCD patients exhibited significantly reduced Glx/Cr levels in the resting thalamus. The levels of resting thalamic Glu/Cr and Glx/Cr in OCD patients with PSQ were significantly lowest. OCD patients had significantly lower correct rates on Go tasks, higher error rates on Nogo tasks, and longer error average response times (EART) to the Nogo task. OCD patients with PSQ demonstrated the highest Nogo task error rate and the longest EART to Nogo task. Furthermore, PSQI scores exhibited negative correlations with Glu/Cr and Glx/Cr in the resting thalamus.
OCD patients with PSQ demonstrated reduced levels of thalamic resting Glx and more pronounced response inhibitory function impairment. Aberrant neurometabolite levels in critical brain regions, coupled with heightened response inhibition function deficits, may be a neurobiological basis for the PSQ that OCD patients generally exhibit.
Individualized, connectome-based, non-invasive stimulation of OCD deep-brain targets: A proof-of-concept
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Treatment-resistant obsessive-compulsive disorder (OCD) generally improves with deep-brain stimulation (DBS), thought to modulate neural activity at both the implantation site and in connected brain regions. However, its invasive nature, side-effects, and lack of customization, make non-invasive treatments preferable. Harnessing the established remote effects of cortical transcranial magnetic stimulation (TMS), connectivity-based approaches have emerged for depression that aim at influencing distant regions connected to the stimulation site. We here investigated whether effective OCD DBS targets (here subthalamic nucleus [STN] and nucleus accumbens [NAc]) could be modulated non-invasively with TMS. In a proof-of-concept study with nine healthy individuals, we used 7T magnetic resonance imaging (MRI) and probabilistic tractography to reconstruct the fiber tracts traversing manually segmented STN/NAc. Two TMS targets were individually selected based on the strength of their structural connectivity to either the STN, or both the STN and NAc. In a sham-controlled, within-subject cross-over design, TMS was administered over the personalized targets, located around the precentral and middle frontal gyrus. Resting-state functional 3T MRI was acquired before, and at 5 and 25 min after stimulation to investigate TMS-induced changes in the functional connectivity of the STN and NAc with other regions of the brain. Static and dynamic seed-to-voxel correlation analyses were conducted. TMS over both targets was able to modulate the functional connectivity of the STN and NAc, engaging both overlapping and distinct regions, and unfolding following different temporal dynamics. Given the relevance of the engaged connected regions to OCD pathology, we argue that a personalized, connectivity-based procedure is worth investigating as potential treatment for refractory OCD.
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Trends in Cognitive Sciences

ReviewSpecial Issue: Cognition in Neuropsychiatric DisordersObsessive-compulsive disorder: beyond segregated cortico-striatal pathways

Section snippets

The current model of OCD

Why is the CSTC model insufficient?

The mOFC and lOFC

The ACC: error processing and fear expression

The amygdala and OCD

What is next in OCD research?

Concluding remarks

Disclosure Statement

Acknowledgments

Glossary

Behav. Brain Res.

Med. Clin. North Am.

Trends Neurosci.

Neuron

Psychiatr. Clin. North Am.

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Neurosci. Biobehav. Rev.

Prog. Neurobiol.

Prog. Brain Res.

Behav. Brain Res.

Neuroimage

Biol. Psychiatry

Neuron

J. Psychiatr. Res.

Neuropsychopharmacology

Biol. Psychiatry

Biol. Psychiatry

Physiol. Behav.

Brain Res. Cogn. Brain Res.

Neuroimage

Psychiatry Res.

Neuron

Behav. Brain Res.

Biol. Psychiatry

Neuroimage

Biol. Psychiatry

Neurosci. Lett.

Biol. Psychiatry

Psychiatr. Clin. North Am.

Biol. Psychol.

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

J. Psychiatr. Res.

Behav. Res. Ther.

Neuropharmacology

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Annu. Rev. Neurosci.

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls

Arch. Gen. Psychiatry

Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder

Am. J. Psychiatry

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

Arch. Gen. Psychiatry

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy

Arch. Gen. Psychiatry

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder

Arch. Gen. Psychiatry

Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography

Arch. Gen. Psychiatry

Fronto-striato-limbic hyperactivation in obsessive-compulsive disorder during individually tailored symptom provocation

Psychophysiology

Functional anatomy of obsessive-compulsive phenomena

Br. J. Psychiatry

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder

Br. J. Psychiatry Suppl.

Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis

Arch. Gen. Psychiatry

Neuroimaging and the neuroanatomy of PTSD

CNS Spectr.

Review
Special Issue: Cognition in Neuropsychiatric Disorders
Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways