Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.
paper
Cited
Public
- Authors
- Shephard, Elizabeth; Stern, Emily R; van den Heuvel, Odile A; Costa, Daniel L C; Batistuzzo, Marcelo C; Godoy, Priscilla B G; Lopes, Antonio C; Brunoni, Andre R; Hoexter, Marcelo Q; Shavitt, Roseli G; Reddy, Y C Janardhan; Lochner, Christine; Stein, Dan J; Simpson, H Blair; Miguel, Euripedes C
- Year
- 2021
- Journal
- Molecular psychiatry
- PMID
- 33414496
- DOI
- 10.1038/s41380-020-01007-8
- PMCID
- PMC8260628
An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.
Five circuits involved in OCDaccording to van den Heuvel et al. (2016) [16]. The fronto-limbic circuit (red) includes the amygdala and ventromedial prefrontal cortex (vmPFC) and is involved in producing emotional responses, such as fear and anxiety. The sensorimotor circuit (green) includes the supplementary motor area (SMA), putamen and thalamus and is involved in producing and controlling motor behavior and the integration of sensory information. The ventral cognitive circuit (yellow) includes the inferior frontal gyrus (IFG), ventrolateral prefrontal cortex (vlPFC), ventral caudate and thalamus and is involved in self-regulatory behavioral control. The ventral affective circuit (purple) includes the orbitofrontal cortex, nucleus accumbens (NAcc) and thalamus and is involved in processing and responding to reward. The dorsal cognitive circuit (blue) includes the dorsolateral prefrontal cortex (dlPFC), dorsomedial prefrontal cortex (dmPFC), dorsal caudate and thalamus and is involved in executive functions (e.g. working memory, planning) and emotion regulation.
The fronto-limbic circuitincludes the amygdala and ventromedial prefrontal cortex (vmPFC, consisting of ventral orbitofrontal cortex, ventral anterior cingulate cortex and the ventral part of medial frontal gyrus). These regions are structurally and functionally connected with each other to form a network that generates emotional responses (amygdala and NAcc) and evaluates whether those responses are appropriate or require regulation (vmPFC). The fronto-limbic circuit is connected with the hippocampus and regions from other circuits that are involved in top-down behavioral control, including the dorsolateral prefrontal cortex (dlPFC) from the dorsal cognitive circuit, and can recruit these regions to dampen fronto-limbic activity thereby facilitating emotional regulation.
The sensorimotor circuitincludes cortical and subcortical regions involved in the generation and control of motor behaviours (primary motor cortex - precentral gyrus, supplementary motor area, putamen, globus pallidus and thalamus) and the integration of sensory information (postcentral gyri, secondary somatosensory cortex, insula).
The ventral cognitive circuitincludes prefrontal (inferior frontal gyrus, ventrolateral prefrontal cortex) and subcortical regions (ventral caudate and thalamus) involved in self-regulatory functions. The inferior frontal gyrus (IFG), particularly in the right hemisphere, and ventral caudate together act as a “braking system”, which implements response inhibition, the ability to withhold inappropriate responses.
The ventral affective circuitincludes the orbitofrontal cortex (OFC), ventral striatum (particularly the nucleus accumbens, NAcc) and the thalamus. This circuit is crucially involved in reward functions which are largely mediated by dopaminergic signaling.
The dorsal cognitive circuitinvolves the pre-supplementary motor area (pre-SMA), dorsolateral PFC (dlPFC), dorsomedial PFC (dmPFC), dorsal caudate and thalamus and handles executive functions such as working memory and planning/organization and emotion regulation.
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| Name | Type |
|---|---|
| addiction | phenotype |
| ADHD | phenotype |
| Age-at-onset local | phenotype |
| ALIC local | anatomy |
| amisulpride local | drug |
| amygdala | anatomy |
| amygdala-vmPFC functional connectivity local | phenotype |
| anhedonia | phenotype |
| anterior cingulate cortex | anatomy |
| antipsychotics | drug |
| anxiety | phenotype |
| anxiety ratings local | phenotype |
| arousal | phenotype |
| attentional functioning local | phenotype |
| attention deficit hyperactivity disorder | phenotype |
| bed nucleus of the stria terminalis | anatomy |
| brain circuits | anatomy |
| caudate nucleus | anatomy |
| cerebellar circuit local | anatomy |
| Checking symptoms local | phenotype |
| cingulate cortex | anatomy |
| Cingulate motor area | anatomy |
| cingulum | anatomy |
| circuits local | anatomy |
| clinical profiles local | phenotype |
| Cognitive behavioral therapy | drug |
| Cognitive reappraisal local | drug |
| comorbidity | phenotype |
| compulsions local | phenotype |
| Compulsions local | phenotype |
| compulsive behavior | phenotype |
| compulsive checking local | phenotype |
| Compulsive Checking local | phenotype |
| compulsivity | phenotype |
| contamination anxiety local | phenotype |
| Contamination concerns local | phenotype |
| contamination obsessions local | phenotype |
| Contamination obsessions local | phenotype |
| contamination-related OCD patients local | cohort |
| Cortical Sensorimotor Areas local | anatomy |
| cortico-striatal-thalamo-cortical circuit local | anatomy |
| cortico-striato-thalamo-cortical circuits local | anatomy |
| Course of illness local | phenotype |
| deep brain stimulation | drug |
| deep TMS local | drug |
| Degree of insight local | phenotype |
| depression | phenotype |
| dirty hands sensation local | phenotype |
| distinct neurocircuits local | anatomy |
| dlPFC | anatomy |
| dopamine | drug |
| Dopaminergic reward signaling local | drug |
| dorsal cognitive circuit local | anatomy |
| Dorsal Cognitive Circuitry local | anatomy |
| dorsal prefrontal cortex | anatomy |
| dorsal striatum | anatomy |
| dorsolateral prefrontal cortex | anatomy |
| dorsomedial prefrontal cortex | anatomy |
| dysregulated fear local | phenotype |
| Dysregulated Fear local | phenotype |
| Effective response inhibition local | phenotype |
| Emotion | phenotype |
| emotional responses local | phenotype |
| emotion regulation | phenotype |
| ENIGMA | cohort |
| excessive habit formation local | phenotype |
| Excessive habit formation local | phenotype |
| Excessive Habit-Formation local | phenotype |
| excessive hand washing local | phenotype |
| Executive Dysfunctions local | phenotype |
| executive function | phenotype |
| executive functioning | phenotype |
| executive function problems local | phenotype |
| Exposure and response prevention | drug |
| extra-cephalic region local | anatomy |
| fear | phenotype |
| fear/anxiety regulation local | phenotype |
| fear distress ratings local | phenotype |
| fear extinction | phenotype |
| feeling dirty under the skin local | phenotype |
| Financial costs local | phenotype |
| fMRI-based neurofeedback local | drug |
| fMRI-neurofeedback local | drug |
| fronto-limbic | anatomy |
| Fronto-limbic dysfunction local | phenotype |
| Fronto-limbic structures local | anatomy |
| Fronto-Limbic Structures local | anatomy |
| fronto-parietal circuit local | anatomy |
| fronto-parietal network | anatomy |
| frontostriatal circuitry | anatomy |
| Functional impairments local | phenotype |
| generalized anxiety disorder | phenotype |
| goal-directed behavior | phenotype |
| gray matter | anatomy |
| habit formation | phenotype |
| Habit-like compulsions local | phenotype |
| Habit-reversal therapy local | drug |
| Habit-reversal training local | drug |
| habits | phenotype |
| habitual behavior | phenotype |
| Harm concerns local | phenotype |
| H-coil TMS local | drug |
| high-frequency rTMS | drug |
| high trait contamination obsessions cohort local | cohort |
| Impaired Memory Functions local | phenotype |
| Incompleteness local | phenotype |
| Increased mortality local | phenotype |
| inferior frontal gyrus | anatomy |
| inferior parietal lobe | anatomy |
| inferior parietal lobule | anatomy |
| inferior parietal regions local | anatomy |
| inhibitory control | phenotype |
| insula | anatomy |
| Intolerance of uncertainty local | phenotype |
| intrusive thoughts | phenotype |
| IU local | phenotype |
| lateral prefrontal cortex | anatomy |
| left dlPFC | anatomy |
| limbic regions | anatomy |
| low frequency rTMS local | drug |
| low-frequency rTMS | drug |
| medial forebrain bundle | anatomy |
| methylphenidate | drug |
| mood disorders | phenotype |
| motor cortex | anatomy |
| Motor/premotor regions local | anatomy |
| mPFC | anatomy |
| NAcc | anatomy |
| NCT03239210 local | cohort |
| Neural network alterations local | phenotype |
| non-psychiatric controls local | cohort |
| non-psychiatric participants local | cohort |
| Non-psychiatric participants local | cohort |
| non-psychiatric volunteers local | cohort |
| norepinephrine | drug |
| not-just-right experiences local | phenotype |
| Not-just-right experiences local | phenotype |
| nucleus accumbens | anatomy |
| obsessions local | phenotype |
| Obsessions local | phenotype |
| obsessive-compulsive disorder | phenotype |
| Obsessive-compulsive severity | phenotype |
| OCD | phenotype |
| OCD-related neurocircuit local | anatomy |
| OCD+SP local | cohort |
| OCD-SP local | cohort |
| OCD symptom severity local | phenotype |
| OCD Treatment Trials local | cohort |
| ondansetron | drug |
| orbitofrontal cortex | anatomy |
| ordering compulsions local | phenotype |
| pallidum | anatomy |
| paracentral lobule | anatomy |
| Parietal somatosensory regions local | anatomy |
| pathological doubt local | phenotype |
| Pathological Doubt local | phenotype |
| patients with generalized anxiety disorder local | cohort |
| patients with OCD local | cohort |
| patients with OCD and/or depression local | cohort |
| Patients with TS local | cohort |
| physiological changes associated with fear and anxiety local | phenotype |
| planning impairment local | phenotype |
| positive arousal local | phenotype |
| postcentral gyrus | anatomy |
| posterior putamen local | anatomy |
| pramipexole local | drug |
| precentral gyrus | anatomy |
| Prefrontal-Amygdala Functional Connectivity local | anatomy |
| prefrontal cortex | anatomy |
| prefrontal regions | anatomy |
| premonitory urges local | phenotype |
| Premonitory urges local | phenotype |
| premotor cortex | anatomy |
| pre-supplementary motor area | anatomy |
| psychiatric symptoms | phenotype |
| psychosis | phenotype |
| putamen | anatomy |
| quality of life | phenotype |
| racing heart local | phenotype |
| Refractory OCD patients local | cohort |
| response inhibition | phenotype |
| response inhibition impairments local | phenotype |
| reward | phenotype |
| Reward Alterations local | phenotype |
| reward responsiveness local | phenotype |
| reward system | anatomy |
| right dlPFC | anatomy |
| rTMS | drug |
| schizophrenia | phenotype |
| selective serotonin reuptake inhibitors | drug |
| sensorimotor area local | anatomy |
| sensorimotor circuit | anatomy |
| sensorimotor circuitry local | anatomy |
| sensory tics local | phenotype |
| Serotonergic raphe nuclei local | anatomy |
| somatosensory cortex | anatomy |
| SP | phenotype |
| SSRIs | drug |
| STN | anatomy |
| striatum | anatomy |
| subcortical regions | anatomy |
| subjective sensory experiences local | phenotype |
| substance use | phenotype |
| subthalamic nucleus | anatomy |
| supplementary motor area | anatomy |
| Symmetry preoccupation local | phenotype |
| symptom dimension | phenotype |
| symptom severity | phenotype |
| Taboo thoughts local | phenotype |
| tactile sensation of feeling dirty local | phenotype |
| tDCS | drug |
| temporal region | anatomy |
| thalamus | anatomy |
| theta oscillations | phenotype |
| tics | phenotype |
| tic severity | phenotype |
| tic symptom severity local | phenotype |
| Tourette syndrome | phenotype |
| treatment-refractory OCD patients local | cohort |
| treatment-refractory patients local | cohort |
| Treatment-resistant obsessive-compulsive disorder local | phenotype |
| treatment-resistant OCD local | phenotype |
| Treatment-resistant OCD patients local | cohort |
| treatment response | phenotype |
| TS | cohort |
| Uncertain threat local | phenotype |
| uncertainty | phenotype |
| VC/VS local | anatomy |
| ventral affective circuit local | anatomy |
| Ventral affective circuit local | anatomy |
| Ventral anterior limb of the internal capsule local | anatomy |
| ventral cognitive circuit local | anatomy |
| Ventral cognitive circuit local | anatomy |
| ventral striatum | anatomy |
| ventromedial prefrontal cortex | anatomy |
| visual emotion processing areas local | anatomy |
| washing and cleaning compulsions local | phenotype |
| washing compulsions local | phenotype |
| Washing symptoms local | phenotype |
| white matter | anatomy |
| White matter networks local | anatomy |
| working memory | phenotype |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. | 2025 | 40360802 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
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| Habit as a therapeutic component in psychological treatment for obsessive-compulsive disorder: A randomised controlled feasibility study. | Pereira de Souza AMFL et al. | — | 2026 | → |
| Human orbitofrontal neural activity is linked to obsessive-compulsive behavioral dynamics. | Nho YH et al. | — | 2026 | → |
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| Neurofeedback interventions for obsessive-compulsive and related disorders: Current evidence and future directions. | Zhang K et al. | — | 2026 | → |
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| Sensorimotor circuit connectivity as a candidate biomarker for responsiveness to sertraline in obsessive-compulsive disorder. | Bai T et al. | — | 2026 | → |
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| Abnormal intrinsic brain activity of the sensory-motor area as a predictor of the response to selective serotonin reuptake inhibitors in treatment-naïve obsessive-compulsive disorder. | Wang H et al. | — | 2025 | → |
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| Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. | Strom NI et al. | — | 2025 | → |
| Increased Amygdala Activation During Symptom Provocation Predicts Response to Combined Repetitive Transcranial Magnetic Stimulation and Exposure Therapy in Obsessive-Compulsive Disorder in a Randomized Controlled Trial. | Houben M et al. | — | 2025 | → |
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| MAGNITUDE: Transcranial Magnetic Stimulation for Treatment-Resistant Obsessive-Compulsive Disorder: A Randomized Sham-Controlled Phase II Trial Protocol. | Rech L et al. | — | 2025 | → |
| Mechanisms and interventions promoting healthy frontostriatal dynamics in obsessive-compulsive disorder. | Naze S et al. | — | 2025 | → |
| Multitarget neurostimulation of the deep brain: clinical opportunities, challenges, and emerging technologies. | Del Sesto MJ et al. | — | 2025 | → |
| Negative Valence in Obsessive-Compulsive Disorder: A Worldwide Mega-Analysis of Task-Based Functional Neuroimaging Data of the ENIGMA-OCD Consortium. | Dzinalija N et al. | — | 2025 | → |
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| Serum metabolites and inflammation predict brain functional connectivity changes in Obsessive-Compulsive disorder. | Chen G et al. | — | 2025 | → |
| The deer mouse (Peromyscus maniculatus bairdii) as a model organism to explore the naturalistic psychobiological mechanisms contributing to compulsive-like rigidity: A narrative overview of advances and opportunities. | Theron V et al. | — | 2025 | → |
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| The Role of Epigenetics in the Pathogenesis and Potential Treatment of Obsessive-compulsive Disorder. | Peedicayil J | — | 2025 | → |
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| A systematic review of structural neuroimaging markers of psychotherapeutic and pharmacological treatment for obsessive-compulsive disorder. | Moreau AL et al. | — | 2024 | → |
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