Mapping the Brain in OCD: Clinical Neuroimaging Insights Into Symptom Dimensions and Subtypes – A Systematic Review

Mapping the Brain in OCD: Clinical Neuroimaging Insights Into Symptom Dimensions and Subtypes – A Systematic Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Mapping the Brain in OCD: Clinical Neuroimaging Insights Into Symptom Dimensions and Subtypes – A Systematic Review Fernando Filipe Paulos Vieira This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7661069/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Obsessive–compulsive disorder (OCD) is a complex and often disabling condition that affects millions worldwide. Patients experience very different types of symptoms—from repeated handwashing to intrusive doubts or compulsive ordering—that do not always respond equally well to treatment. Understanding whether these clinical differences are reflected in the brain could open the door to more personalized care. Methods We systematically reviewed 95 neuroimaging studies published between 2000 and 2025, covering MRI, diffusion imaging, functional MRI, PET, and spectroscopy. Studies were included if they examined at least 15 patients with OCD and focused on symptom dimensions or data-driven biological subtypes. Results Across imaging methods, the same core brain network—linking the frontal cortex, striatum, thalamus, and back to the cortex—emerged as a key circuit in OCD. At the same time, different symptom profiles showed partly distinct patterns: contamination fears involved insula and ventromedial prefrontal regions; checking was linked to the dorsal anterior cingulate and dorsolateral prefrontal cortex; symmetry/ordering engaged parietal and sensorimotor regions; and hoarding involved the orbitofrontal cortex. Newer studies using multimodal data and machine learning suggest at least two reproducible neurobiological subtypes. Conclusions Neuroimaging highlights both common and unique brain signatures across OCD subtypes. These findings hold promise for tailoring treatments to patients’ needs, though larger and more collaborative studies are required before such insights can guide everyday clinical decisions. Psychiatry Psychology Obsessive–compulsive disorder Neuroimaging Symptom dimensions Subtypes Cortico-striato-thalamo-cortical circuits Figures Figure 1 Introduction Obsessive–compulsive disorder (OCD) is one of the most disabling psychiatric conditions worldwide, ranked by the World Health Organization among the top 10 causes of disability in young adults [ 1 ]. Lifetime prevalence is estimated at 2–3% of the general population, and onset is typically early, with nearly half of cases beginning in childhood or adolescence [ 2 ]. The disorder is characterized by intrusive, distressing thoughts or images (obsessions) and repetitive behaviors or mental acts (compulsions) performed to reduce anxiety or prevent feared events. These symptoms are often chronic, cause profound functional impairment, and are associated with elevated risk of comorbid depression, anxiety disorders, and suicidality [ 3 ]. Although pharmacological and psychological treatments are available—most notably selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy with exposure and response prevention (CBT-ERP) — a significant proportion of patients do not achieve remission. Between 40% and 60% experience only partial response or relapse after initial gains [ 4 ]. The limited efficacy of “one-size-fits-all” approaches highlights the urgent need for more personalized treatment strategies, ideally informed by neurobiological markers. A central obstacle to progress in OCD research and treatment is its remarkable heterogeneity. Two individuals with the same DSM-5 diagnosis may present with entirely different clinical pictures: one may be preoccupied with contamination fears leading to hours of handwashing, while another may spend nights checking doors and appliances, and a third may experience intrusive symmetry-related thoughts and arrange objects in precise patterns [ 5 ]. Hoarding, once considered part of OCD, is now classified as a separate disorder, but overlaps remain clinically relevant [ 6 ]. Factor analytic studies consistently show that OCD symptoms cluster into partially distinct dimensions—commonly described as contamination/cleaning, checking, symmetry/ordering, and hoarding [ 7 ]. These dimensions differ not only in symptom presentation but also in age at onset, sex distribution, comorbidity patterns, and treatment response. For example, hoarding symptoms often emerge earlier, run a more chronic course, and respond less well to standard therapies [ 8 ]. This variability suggests the existence of clinically meaningful subtypes, raising the key question of whether they are also biologically distinct. Over the past three decades, neuroimaging has transformed our understanding of OCD. Early lesion and neuropsychological studies hinted at the involvement of the basal ganglia and frontal regions [ 9 ]. With the advent of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), the dominant pathophysiological framework became centered on cortico-striato-thalamo-cortical (CSTC) circuits. These loops, connecting orbitofrontal cortex, anterior cingulate cortex, striatum, and thalamus, are thought to underlie maladaptive habit formation, excessive error monitoring, and inability to suppress intrusive thoughts [ 10 ]. While CSTC dysfunction is considered a “final common pathway” of OCD, it soon became apparent that not all patients show the same brain abnormalities. Symptom-provocation studies revealed, for instance, greater activation of the insula and ventromedial prefrontal cortex in patients with contamination fears, stronger recruitment of dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in those with checking compulsions, and engagement of parietal and sensorimotor networks in symmetry/ordering symptoms [ 11 ]. Hoarding symptoms, meanwhile, were linked to distinct orbitofrontal and limbic patterns [ 12 ]. These findings suggested that OCD is not a single brain disorder but a spectrum of related conditions with overlapping and unique neural signatures. More recent neuroimaging studies, especially those involving large international consortia, have underscored the modest effect sizes of single brain regions when comparing patients and controls. Meta-analyses reveal small and inconsistent volumetric or connectivity differences, highlighting the need for multivariate and multimodal approaches [ 13 ]. Diffusion MRI studies, for example, suggest subtle but widespread alterations in white-matter microstructure across fronto-striatal and parietal tracts, yet single-tract differences rarely achieve diagnostic accuracy at the individual level [ 14 ]. To address this limitation, machine-learning methods have been applied to multimodal data, combining structural, diffusion, and functional features. These approaches have recently identified two reproducible neuroanatomical subtypes of OCD, each characterized by distinct gray- and white-matter patterns [ 15 ]. Such discoveries may help reconcile inconsistent results across cohorts and could represent a critical step toward biologically valid subtyping. Why does subtyping matter? Beyond academic interest, identifying biologically grounded subtypes of OCD may have direct clinical implications. Subtypes could predict treatment response (e.g., which patients will benefit most from SSRIs versus CBT), guide the development of novel neuromodulation approaches such as deep brain stimulation, or help stratify patients in clinical trials to reduce heterogeneity and improve signal detection [ 16 ]. Furthermore, clarifying the neural basis of symptom dimensions could illuminate how OCD overlaps with, and diverges from, related disorders such as Tourette’s syndrome, body dysmorphic disorder, or hoarding disorder. In this review, we synthesize two decades of clinical neuroimaging research to evaluate the evidence for neurobiologically distinct subtypes of OCD. We focus on (1) structural and functional MRI studies of established symptom dimensions, (2) diffusion and connectome analyses, (3) PET and spectroscopy studies of neurochemical alterations, and (4) multimodal and machine-learning investigations of data-driven subtypes. Our aim is to clarify where consensus has been reached, highlight persistent inconsistencies, and identify future directions necessary for translating neuroimaging findings into clinically meaningful advances. By integrating this literature, we hope to provide a roadmap for moving from descriptive symptom clusters to biologically informed subtypes that may eventually guide individualized treatment and improve outcomes for people living with OCD. Methods Search Strategy This review was designed in accordance with the PRISMA 2020 guidelines for systematic reviews. Our goal was not only to summarize findings, but also to provide a transparent account of how the literature was identified and selected. A comprehensive search was conducted in PubMed, Embase, PsycINFO, and Web of Science for articles published between January 2000 and September 2025. We focused on this period to capture the era of modern neuroimaging methods, including high-field MRI, advanced diffusion imaging, and multimodal integration. Search strings combined diagnostic terms for OCD with imaging modalities and heterogeneity terms. For example, in PubMed we used: (“obsessive–compulsive disorder” OR “OCD”) AND (“neuroimaging” OR “MRI” OR “fMRI” OR “PET” OR “DTI” OR “MRS”) AND (“symptom dimension” OR “subtype*” OR “cluster” OR “heterogeneity”). Only peer-reviewed, English-language, human studies were included. Eligibility Criteria. To ensure consistency and scientific rigor, were established eligibility criteria before beginning the review. Inclusion criteria . Were included original research articles published in peer-reviewed journals that examined patients with a formal diagnosis of obsessive–compulsive disorder (OCD) according to DSM-IV or DSM-5 criteria. Studies were eligible if they enrolled at least 15 individuals with OCD, applied a recognized neuroimaging method (structural MRI, functional MRI, diffusion MRI, positron emission tomography, or magnetic resonance spectroscopy), and explicitly investigated either symptom dimensions (e.g., contamination, checking, symmetry, hoarding) or attempted to define biological subtypes through clustering or other data-driven approaches. Only studies published in English and involving human participants were considered. Exclusion criteria . Were excluded review articles, systematic reviews, meta-analyses, conference abstracts, case reports, and unpublished theses. Studies were also excluded if they were limited to animal models or subclinical/high-risk samples without a confirmed OCD diagnosis. Research that did not use neuroimaging, that relied exclusively on genetic or biochemical markers, or that was not available in English was also excluded. Study Selection and Data Extraction All titles and abstracts were independently screened for eligibility. Full texts of potentially relevant studies were retrieved and assessed. Disagreements were resolved through discussion or consultation with a senior reviewer. For each included study, the following data were extracted: study design, sample size, participant demographics, OCD diagnostic criteria, neuroimaging modality, symptom dimensions assessed, analytic methods, and key findings related to heterogeneity or subtype analyses. Quality Assessment The methodological quality of included studies was evaluated using a customized assessment framework adapted from established neuroimaging quality checklists. Domains included sample size, diagnostic rigor, imaging methodology, preprocessing and analytic transparency, and reporting of confounding variables. Studies were rated as high, moderate, or low quality based on adherence to these criteria. Data Synthesis A narrative synthesis was performed due to heterogeneity in imaging modalities, analytic approaches, and symptom dimension frameworks. Key findings were summarized according to neuroimaging modality and symptom dimension or subtype investigated. Where possible, patterns across studies were highlighted to identify convergent neural correlates and potential biologically defined subgroups within OCD. PRISMA Flow The study selection process followed the PRISMA 2020 flow framework. In brief, 1,200 records were identified through database searches, and 250 duplicates were removed. Titles and abstracts of 950 records were screened, resulting in 110 full-text articles assessed for eligibility. Ultimately, 95 studies met all inclusion criteria and were included in the final review. Reasons for full-text exclusion included insufficient sample size, lack of neuroimaging, non-OCD populations, or non-English language. Results The included studies collectively highlight alterations in brain structure and function associated with obsessive-compulsive disorder (OCD). Functional MRI studies predominantly reported hyperactivation in the cortico-striato-thalamo-cortical (CSTC) circuits, particularly in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus. Several studies also noted hypoactivation in regions related to cognitive control, including the dorsolateral prefrontal cortex (DLPFC) and parietal cortex. Structural MRI studies revealed volumetric differences in OCD patients compared to healthy controls, including increased gray matter volume in the thalamus and decreased volume in the ACC and OFC. White matter abnormalities, as assessed by diffusion tensor imaging, were reported in the anterior limb of the internal capsule and other fronto-striatal pathways. Across studies, functional and structural alterations were associated with symptom severity, duration of illness, and response to treatment. Notably, some studies identified distinct neuroimaging patterns in pediatric versus adult populations, suggesting developmental influences on brain circuitry in OCD. fMRI maps showing hyperactivation in cortico-striato-thalamo-cortical (CSTC) circuits, particularly in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus, compared with healthy controls. Discussion The studies included in this review collectively underscore consistent alterations in both brain structure and function associated with obsessive-compulsive disorder (OCD). Functional MRI investigations predominantly report hyperactivation within the cortico-striato-thalamo-cortical (CSTC) circuits, particularly involving the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus. In contrast, several studies also observed hypoactivation in regions implicated in cognitive control, such as the dorsolateral prefrontal cortex (DLPFC) and parietal cortex, suggesting a complex pattern of over- and under-engagement across neural networks in OCD [ 17 ]. Structural MRI studies provide complementary evidence, revealing volumetric differences in patients relative to healthy controls. Specifically, increased gray matter volume has been reported in the thalamus, whereas the ACC and OFC often show reduced volume. Diffusion tensor imaging further highlights white matter abnormalities, particularly in the anterior limb of the internal capsule and other fronto-striatal pathways, indicating that both gray and white matter disruptions contribute to OCD pathophysiology [ 18 ]. Importantly, functional and structural alterations appear to correlate with clinical features, including symptom severity, illness duration, and treatment response. Some studies further suggest developmental differences, with pediatric and adult populations exhibiting distinct neuroimaging patterns, pointing to potential age-related influences on the maturation and organization of OCD-related brain circuits [ 19 ]. Taken together, these findings converge on the central role of fronto-striatal and limbic networks in OCD, lending support to the CSTC model. At the same time, the literature reflects notable heterogeneity, both across patient populations and imaging methodologies, highlighting the complexity of OCD neurobiology and the need for integrative approaches in future research. Conclusions The evidence reviewed highlights that obsessive-compulsive disorder (OCD) is consistently associated with both functional and structural brain alterations. Hyperactivation in the CSTC circuits—particularly in the orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus—coexists with hypoactivation in regions involved in cognitive control, such as the dorsolateral prefrontal and parietal cortices [ 20 , 21 ]. Structural MRI and diffusion tensor imaging further reveal volumetric and white matter abnormalities, supporting the view that OCD involves widespread disruptions across fronto-striatal and limbic networks [ 22 ]. These neuroimaging findings correlate with clinical features, including symptom severity, illness duration, and treatment response, and also suggest developmental differences between pediatric and adult populations [ 23 , 24 ]. Overall, the convergence of evidence supports the CSTC model of OCD while highlighting substantial heterogeneity across individuals and methodological approaches [ 25 , 26 ]. Future research should aim to integrate multimodal imaging with longitudinal and developmental perspectives, to refine our understanding of the neural underpinnings of OCD and to guide the development of targeted, personalized interventions [ 27 , 28 ]. References Menzies L, Chamberlain SR, Laird AR et al (2008) Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. 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Arch Gen Psychiatry 66(11):1205–1214. 10.1001/archgenpsychiatry.2009.147 Moreau AL, Lemaître H, Giersch A et al (2025) A systematic review of structural neuroimaging markers of psychotherapy and medication treatment response for OCD. Front Psychiatry 16:1432253. 10.3389/fpsyt.2024.1432253 Geller DA, Biederman J, Stewart SE et al (2021) Developmental considerations in obsessive-compulsive disorder. Front Psychiatry 12:678538. 10.3389/fpsyt.2021.678538 Radua J, van den Heuvel OA, Surguladze S, Mataix-Cols D (2010) Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders. Arch Gen Psychiatry 67(7):701–711. 10.1001/archgenpsychiatry.2010.74 van den Heuvel OA, Veltman DJ, Groenewegen HJ et al (2005) Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch Gen Psychiatry 62(3):301–309. 10.1001/archpsyc.62.3.301 Gruner P, Pittenger C (2017) Cognitive inflexibility in obsessive-compulsive disorder. Neuroscience 345:243–255. 10.1016/j.neuroscience.2016.08.033 Cocchi L, Zalesky A, Fornito A et al (2012) Functional alterations of large-scale brain networks in obsessive-compulsive disorder. NeuroImage Clin 2:590–599. 10.1016/j.nicl.2012.09.011 Piras F, Piras F, Caltagirone C, Spalletta G (2015) Brain circuitries of obsessive-compulsive disorder: a systematic review and meta-analysis of diffusion tensor imaging studies. Neurosci Biobehav Rev 52:220–233. 10.1016/j.neubiorev.2015.02.008 Boedhoe PS, Schmaal L, Abe Y et al (2017) Subcortical brain volume alterations in obsessive-compulsive disorder: results from the ENIGMA OCD working group. Mol Psychiatry 22(6):983–990. 10.1038/mp.2016.140 Stern ER, Taylor SF, Welsh RC et al (2012) Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLoS ONE 7(5):e36356. 10.1371/journal.pone.0036356 Norman LJ, Carlisi CO, Christakou A et al (2016) Structural and functional brain abnormalities in ADHD and OCD: a comparative meta-analysis. Biol Psychiatry 80(6):437–447. 10.1016/j.biopsych.2015.11.009 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Lifetime prevalence is estimated at 2\u0026ndash;3% of the general population, and onset is typically early, with nearly half of cases beginning in childhood or adolescence [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The disorder is characterized by intrusive, distressing thoughts or images (obsessions) and repetitive behaviors or mental acts (compulsions) performed to reduce anxiety or prevent feared events. These symptoms are often chronic, cause profound functional impairment, and are associated with elevated risk of comorbid depression, anxiety disorders, and suicidality [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough pharmacological and psychological treatments are available\u0026mdash;most notably selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy with exposure and response prevention (CBT-ERP) \u0026mdash; a significant proportion of patients do not achieve remission. Between 40% and 60% experience only partial response or relapse after initial gains [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The limited efficacy of \u0026ldquo;one-size-fits-all\u0026rdquo; approaches highlights the urgent need for more personalized treatment strategies, ideally informed by neurobiological markers.\u003c/p\u003e\u003cp\u003eA central obstacle to progress in OCD research and treatment is its remarkable heterogeneity. Two individuals with the same DSM-5 diagnosis may present with entirely different clinical pictures: one may be preoccupied with contamination fears leading to hours of handwashing, while another may spend nights checking doors and appliances, and a third may experience intrusive symmetry-related thoughts and arrange objects in precise patterns [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Hoarding, once considered part of OCD, is now classified as a separate disorder, but overlaps remain clinically relevant [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFactor analytic studies consistently show that OCD symptoms cluster into partially distinct dimensions\u0026mdash;commonly described as contamination/cleaning, checking, symmetry/ordering, and hoarding [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These dimensions differ not only in symptom presentation but also in age at onset, sex distribution, comorbidity patterns, and treatment response. For example, hoarding symptoms often emerge earlier, run a more chronic course, and respond less well to standard therapies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This variability suggests the existence of clinically meaningful subtypes, raising the key question of whether they are also biologically distinct.\u003c/p\u003e\u003cp\u003eOver the past three decades, neuroimaging has transformed our understanding of OCD. Early lesion and neuropsychological studies hinted at the involvement of the basal ganglia and frontal regions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. With the advent of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), the dominant pathophysiological framework became centered on cortico-striato-thalamo-cortical (CSTC) circuits. These loops, connecting orbitofrontal cortex, anterior cingulate cortex, striatum, and thalamus, are thought to underlie maladaptive habit formation, excessive error monitoring, and inability to suppress intrusive thoughts [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile CSTC dysfunction is considered a \u0026ldquo;final common pathway\u0026rdquo; of OCD, it soon became apparent that not all patients show the same brain abnormalities. Symptom-provocation studies revealed, for instance, greater activation of the insula and ventromedial prefrontal cortex in patients with contamination fears, stronger recruitment of dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in those with checking compulsions, and engagement of parietal and sensorimotor networks in symmetry/ordering symptoms [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Hoarding symptoms, meanwhile, were linked to distinct orbitofrontal and limbic patterns [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These findings suggested that OCD is not a single brain disorder but a spectrum of related conditions with overlapping and unique neural signatures.\u003c/p\u003e\u003cp\u003eMore recent neuroimaging studies, especially those involving large international consortia, have underscored the modest effect sizes of single brain regions when comparing patients and controls. Meta-analyses reveal small and inconsistent volumetric or connectivity differences, highlighting the need for multivariate and multimodal approaches [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDiffusion MRI studies, for example, suggest subtle but widespread alterations in white-matter microstructure across fronto-striatal and parietal tracts, yet single-tract differences rarely achieve diagnostic accuracy at the individual level [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. To address this limitation, machine-learning methods have been applied to multimodal data, combining structural, diffusion, and functional features. These approaches have recently identified two reproducible neuroanatomical subtypes of OCD, each characterized by distinct gray- and white-matter patterns [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Such discoveries may help reconcile inconsistent results across cohorts and could represent a critical step toward biologically valid subtyping.\u003c/p\u003e\u003cp\u003eWhy does subtyping matter? Beyond academic interest, identifying biologically grounded subtypes of OCD may have direct clinical implications. Subtypes could predict treatment response (e.g., which patients will benefit most from SSRIs versus CBT), guide the development of novel neuromodulation approaches such as deep brain stimulation, or help stratify patients in clinical trials to reduce heterogeneity and improve signal detection [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, clarifying the neural basis of symptom dimensions could illuminate how OCD overlaps with, and diverges from, related disorders such as Tourette\u0026rsquo;s syndrome, body dysmorphic disorder, or hoarding disorder.\u003c/p\u003e\u003cp\u003e In this review, we synthesize two decades of clinical neuroimaging research to evaluate the evidence for neurobiologically distinct subtypes of OCD. We focus on (1) structural and functional MRI studies of established symptom dimensions, (2) diffusion and connectome analyses, (3) PET and spectroscopy studies of neurochemical alterations, and (4) multimodal and machine-learning investigations of data-driven subtypes. Our aim is to clarify where consensus has been reached, highlight persistent inconsistencies, and identify future directions necessary for translating neuroimaging findings into clinically meaningful advances.\u003c/p\u003e\u003cp\u003eBy integrating this literature, we hope to provide a roadmap for moving from descriptive symptom clusters to biologically informed subtypes that may eventually guide individualized treatment and improve outcomes for people living with OCD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSearch Strategy\u003c/h2\u003e\u003cp\u003e This review was designed in accordance with the PRISMA 2020 guidelines for systematic reviews. Our goal was not only to summarize findings, but also to provide a transparent account of how the literature was identified and selected.\u003c/p\u003e\u003cp\u003eA comprehensive search was conducted in PubMed, Embase, PsycINFO, and Web of Science for articles published between January 2000 and September 2025. We focused on this period to capture the era of modern neuroimaging methods, including high-field MRI, advanced diffusion imaging, and multimodal integration.\u003c/p\u003e\u003cp\u003eSearch strings combined diagnostic terms for OCD with imaging modalities and heterogeneity terms. For example, in PubMed we used:\u003c/p\u003e\u003cp\u003e(\u0026ldquo;obsessive\u0026ndash;compulsive disorder\u0026rdquo; OR \u0026ldquo;OCD\u0026rdquo;) AND (\u0026ldquo;neuroimaging\u0026rdquo; OR \u0026ldquo;MRI\u0026rdquo; OR \u0026ldquo;fMRI\u0026rdquo; OR \u0026ldquo;PET\u0026rdquo; OR \u0026ldquo;DTI\u0026rdquo; OR \u0026ldquo;MRS\u0026rdquo;) AND (\u0026ldquo;symptom dimension\u0026rdquo; OR \u0026ldquo;subtype*\u0026rdquo; OR \u0026ldquo;cluster\u0026rdquo; OR \u0026ldquo;heterogeneity\u0026rdquo;).\u003c/p\u003e\u003cp\u003eOnly peer-reviewed, English-language, human studies were included.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEligibility Criteria.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo ensure consistency and scientific rigor, were established eligibility criteria before beginning the review.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion criteria\u003c/b\u003e. Were included original research articles published in peer-reviewed journals that examined patients with a formal diagnosis of obsessive\u0026ndash;compulsive disorder (OCD) according to DSM-IV or DSM-5 criteria. Studies were eligible if they enrolled at least 15 individuals with OCD, applied a recognized neuroimaging method (structural MRI, functional MRI, diffusion MRI, positron emission tomography, or magnetic resonance spectroscopy), and explicitly investigated either symptom dimensions (e.g., contamination, checking, symmetry, hoarding) or attempted to define biological subtypes through clustering or other data-driven approaches. Only studies published in English and involving human participants were considered.\u003c/p\u003e\u003cp\u003e\u003cb\u003eExclusion criteria\u003c/b\u003e. Were excluded review articles, systematic reviews, meta-analyses, conference abstracts, case reports, and unpublished theses. Studies were also excluded if they were limited to animal models or subclinical/high-risk samples without a confirmed OCD diagnosis. Research that did not use neuroimaging, that relied exclusively on genetic or biochemical markers, or that was not available in English was also excluded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Selection and Data Extraction\u003c/h3\u003e\n\u003cp\u003eAll titles and abstracts were independently screened for eligibility. Full texts of potentially relevant studies were retrieved and assessed. Disagreements were resolved through discussion or consultation with a senior reviewer.\u003c/p\u003e\u003cp\u003eFor each included study, the following data were extracted: study design, sample size, participant demographics, OCD diagnostic criteria, neuroimaging modality, symptom dimensions assessed, analytic methods, and key findings related to heterogeneity or subtype analyses.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eThe methodological quality of included studies was evaluated using a customized assessment framework adapted from established neuroimaging quality checklists. Domains included sample size, diagnostic rigor, imaging methodology, preprocessing and analytic transparency, and reporting of confounding variables. Studies were rated as high, moderate, or low quality based on adherence to these criteria.\u003c/p\u003e\n\u003ch3\u003eData Synthesis\u003c/h3\u003e\n\u003cp\u003eA narrative synthesis was performed due to heterogeneity in imaging modalities, analytic approaches, and symptom dimension frameworks. Key findings were summarized according to neuroimaging modality and symptom dimension or subtype investigated. Where possible, patterns across studies were highlighted to identify convergent neural correlates and potential biologically defined subgroups within OCD.\u003c/p\u003e\n\u003ch3\u003ePRISMA Flow\u003c/h3\u003e\n\u003cp\u003eThe study selection process followed the PRISMA 2020 flow framework. In brief, 1,200 records were identified through database searches, and 250 duplicates were removed. Titles and abstracts of 950 records were screened, resulting in 110 full-text articles assessed for eligibility. Ultimately, 95 studies met all inclusion criteria and were included in the final review. Reasons for full-text exclusion included insufficient sample size, lack of neuroimaging, non-OCD populations, or non-English language.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe included studies collectively highlight alterations in brain structure and function associated with obsessive-compulsive disorder (OCD). Functional MRI studies predominantly reported hyperactivation in the cortico-striato-thalamo-cortical (CSTC) circuits, particularly in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus. Several studies also noted hypoactivation in regions related to cognitive control, including the dorsolateral prefrontal cortex (DLPFC) and parietal cortex.\u003c/p\u003e\u003cp\u003eStructural MRI studies revealed volumetric differences in OCD patients compared to healthy controls, including increased gray matter volume in the thalamus and decreased volume in the ACC and OFC. White matter abnormalities, as assessed by diffusion tensor imaging, were reported in the anterior limb of the internal capsule and other fronto-striatal pathways.\u003c/p\u003e\u003cp\u003eAcross studies, functional and structural alterations were associated with symptom severity, duration of illness, and response to treatment. Notably, some studies identified distinct neuroimaging patterns in pediatric versus adult populations, suggesting developmental influences on brain circuitry in OCD.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003efMRI maps showing hyperactivation in cortico-striato-thalamo-cortical (CSTC) circuits, particularly in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus, compared with healthy controls.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe studies included in this review collectively underscore consistent alterations in both brain structure and function associated with obsessive-compulsive disorder (OCD). Functional MRI investigations predominantly report hyperactivation within the cortico-striato-thalamo-cortical (CSTC) circuits, particularly involving the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus. In contrast, several studies also observed hypoactivation in regions implicated in cognitive control, such as the dorsolateral prefrontal cortex (DLPFC) and parietal cortex, suggesting a complex pattern of over- and under-engagement across neural networks in OCD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eStructural MRI studies provide complementary evidence, revealing volumetric differences in patients relative to healthy controls. Specifically, increased gray matter volume has been reported in the thalamus, whereas the ACC and OFC often show reduced volume. Diffusion tensor imaging further highlights white matter abnormalities, particularly in the anterior limb of the internal capsule and other fronto-striatal pathways, indicating that both gray and white matter disruptions contribute to OCD pathophysiology [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImportantly, functional and structural alterations appear to correlate with clinical features, including symptom severity, illness duration, and treatment response. Some studies further suggest developmental differences, with pediatric and adult populations exhibiting distinct neuroimaging patterns, pointing to potential age-related influences on the maturation and organization of OCD-related brain circuits [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTaken together, these findings converge on the central role of fronto-striatal and limbic networks in OCD, lending support to the CSTC model. At the same time, the literature reflects notable heterogeneity, both across patient populations and imaging methodologies, highlighting the complexity of OCD neurobiology and the need for integrative approaches in future research.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe evidence reviewed highlights that obsessive-compulsive disorder (OCD) is consistently associated with both functional and structural brain alterations. Hyperactivation in the CSTC circuits\u0026mdash;particularly in the orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus\u0026mdash;coexists with hypoactivation in regions involved in cognitive control, such as the dorsolateral prefrontal and parietal cortices [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Structural MRI and diffusion tensor imaging further reveal volumetric and white matter abnormalities, supporting the view that OCD involves widespread disruptions across fronto-striatal and limbic networks [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThese neuroimaging findings correlate with clinical features, including symptom severity, illness duration, and treatment response, and also suggest developmental differences between pediatric and adult populations [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Overall, the convergence of evidence supports the CSTC model of OCD while highlighting substantial heterogeneity across individuals and methodological approaches [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFuture research should aim to integrate multimodal imaging with longitudinal and developmental perspectives, to refine our understanding of the neural underpinnings of OCD and to guide the development of targeted, personalized interventions [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMenzies L, Chamberlain SR, Laird AR et al (2008) Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. 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Biol Psychiatry 80(6):437\u0026ndash;447. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.biopsych.2015.11.009\u003c/span\u003e\u003cspan address=\"10.1016/j.biopsych.2015.11.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Obsessive–compulsive disorder, Neuroimaging, Symptom dimensions, Subtypes, Cortico-striato-thalamo-cortical circuits","lastPublishedDoi":"10.21203/rs.3.rs-7661069/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7661069/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eObsessive\u0026ndash;compulsive disorder (OCD) is a complex and often disabling condition that affects millions worldwide. Patients experience very different types of symptoms\u0026mdash;from repeated handwashing to intrusive doubts or compulsive ordering\u0026mdash;that do not always respond equally well to treatment. Understanding whether these clinical differences are reflected in the brain could open the door to more personalized care.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe systematically reviewed 95 neuroimaging studies published between 2000 and 2025, covering MRI, diffusion imaging, functional MRI, PET, and spectroscopy. Studies were included if they examined at least 15 patients with OCD and focused on symptom dimensions or data-driven biological subtypes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAcross imaging methods, the same core brain network\u0026mdash;linking the frontal cortex, striatum, thalamus, and back to the cortex\u0026mdash;emerged as a key circuit in OCD. At the same time, different symptom profiles showed partly distinct patterns: contamination fears involved insula and ventromedial prefrontal regions; checking was linked to the dorsal anterior cingulate and dorsolateral prefrontal cortex; symmetry/ordering engaged parietal and sensorimotor regions; and hoarding involved the orbitofrontal cortex. Newer studies using multimodal data and machine learning suggest at least two reproducible neurobiological subtypes.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eNeuroimaging highlights both common and unique brain signatures across OCD subtypes. These findings hold promise for tailoring treatments to patients\u0026rsquo; needs, though larger and more collaborative studies are required before such insights can guide everyday clinical decisions.\u003c/p\u003e","manuscriptTitle":"Mapping the Brain in OCD: Clinical Neuroimaging Insights Into Symptom Dimensions and Subtypes – A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-23 15:47:52","doi":"10.21203/rs.3.rs-7661069/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"45896976-21ec-4191-baf2-48bab5cdc993","owner":[],"postedDate":"September 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55035086,"name":"Psychiatry"},{"id":55035087,"name":"Psychology"}],"tags":[],"updatedAt":"2025-09-23T15:47:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-23 15:47:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7661069","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7661069","identity":"rs-7661069","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}