Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2025 May 15.
Published in final edited form as: J Affect Disord. 2024 Feb 19;353:48–51. doi: 10.1016/j.jad.2024.02.065

Sensory over-responsivity and orbitofrontal cortex connectivity in obsessive-compulsive disorder

Katherine A Collins 1, Nicolette Recchia 1,2, Goi Khia Eng 1,2, Jeanmarie R Harvey 1,2, Russell H Tobe 1,3, Emily R Stern 1,2
PMCID: PMC11066885  NIHMSID: NIHMS1972674  PMID: 38382815

Abstract

Background:

Sensory over-responsivity (SOR) in obsessive-compulsive disorder (OCD) is associated with illness severity and functional impairment. However, the neural substrates of SOR in OCD have not yet been directly probed.

Methods:

We examined resting-state global functional connectivity markers of SOR in 119 adults with OCD utilizing the CONN-fMRI Functional Connectivity Toolbox for SPM (v21a). We quantified SOR with the sensory sensitivity and sensory avoiding subscales of the Adult and Adolescent Sensory Profile (AASP). We also measured: OCD severity, with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Obsessive-Compulsive Inventory-Revised (OCI-R); sensory phenomena with the Sensory Phenomena Scale (SPS); general anxiety, with the Beck Anxiety Inventory (BAI); and depressive symptomatology, with Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR).

Results:

There was a significant positive relationship of SOR with global connectivity in anterior and medial OFC (Brodmann’s area 11, k=154, x=14, y=62, z=−18, whole-brain corrected at FWE p<0.05).

Limitations:

Future investigations should explore neural responses to sensory stimulation tasks in OCD and compare findings with those obtained in other conditions also characterized by high SOR, such as autism spectrum disorder.

Conclusions:

This study implicates OFC functional connectivity as a neurobiological mechanism of SOR in OCD and suggests that the substrates of SOR in OCD may be dissociable from both that of other symptoms in OCD, and SOR in other disorders. With replication and extension, the finding may be leveraged to develop and refine treatments for OCD and investigate the pathophysiology of SOR in other conditions.

Keywords: sensory over-responsivity, obsessive-compulsive disorder, functional connectivity

Although the cardinal features of obsessive-compulsive disorder (OCD) include obsessions (ego dystonic intrusive thoughts, images, and urges) and compulsions (repetitive behaviors or mental acts intended to relieve discomfort, American Psychiatric Association, 2013), patients also report aversive sensory experiences not captured in the diagnostic criteria. In particular, OCD is associated with sensory over-responsivity (SOR), defined as an increased sensitivity to and avoidance of certain external sensory stimuli (e.g. lights, sounds, touch), which are subjectively perceived as aversively intense (Miller et al., 2007). Although not frequently studied in OCD, SOR is present in both clinical (Lewin et al., 2015) and non-clinical (Dar et al., 2012; Schwarzlose et al., 2023) samples.

SOR in OCD is positively associated with symptom severity, distress, and functional impairment (Dar et al., 2012; Lewin et al., 2015; Schwarzlose et al., 2023). Elucidating the pathophysiology of SOR in OCD may facilitate development of targeted treatments. However, to our knowledge, the neural substrates of SOR in OCD have not yet been directly probed. Here we examined resting-state functional connectivity markers of SOR in adults with OCD.

Methods

Participants, recruited to participate in one of three studies designed to probe interoceptive neurocircuitry in OCD (Brown et al., 2019; Eng et al., 2020; Stern et al., 2020; Eng et al., 2022; Stern et al., 2022), were enrolled at the Icahn School of Medicine at Mount Sinai (ISMMS), Nathan Kline Institute for Psychiatric Research (NKI), and New York University School of Medicine between May 2017 and August 2021. The study protocol was approved by the Institutional Review Boards at each institution. All participants provided written informed consent. Data were analyzed from 119 adults aged 18–55 meeting DSM-5 criteria for OCD. Exclusions were intellectual disability, lifetime history of bipolar and psychotic disorders, or current moderate to severe alcohol or substance use disorders. Sixty-one participants (51%) were taking psychotropic medications (predominately serotonin reuptake inhibitors, n=50) and 84 (71%) had at least one current comorbid psychiatric disorder (Supplement Tables S1–S2). SOR was measured using the Adult and Adolescent Sensory Profile (AASP, Brown et al., 2001). Participants indicated the frequency with which they engage in a specific behavior (e.g., “I stay away from noisy settings”) or have a relevant affective experience (e.g., “I dislike having my back rubbed”) on a scale of 1 (“almost never, about 5% or less of the time”) to 5 (“almost always, about 95% or more of the time”). Following convention, we quantified SOR by computing the average of the sensory sensitivity and sensory avoidance subscales (15 items each, Dar et al., 2012; Lewin et al., 2015). Values ranging from 1.77 to 2.73 are considered “similar to most people” (Brown and Dunn, 2002). Additional clinical scales measured overall OCD symptom severity (Yale-Brown Obsessive Compulsive Scale, Y-BOCS, Goodman et al., 1989) and sensory phenomena (Sensory Phenomena Scale, SPS, Rosario et al., 2009). Self-report assessments included the Obsessive-Compulsive Inventory-Revised (OCI-R, Foa et al., 2002), Beck Anxiety Inventory (BAI, Beck et al., 1988), and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR, Rush et al., 2003).

MRI scanning occurred on two Siemens 3T scanners (at ISMMS and NKI) with harmonized sequences; site was used as a covariate for all group-level analyses as recommended (Glover et al., 2012). All participants underwent an eight-minute resting-state scan (480 volumes, TR=1s, 2.1mm isotropic voxels) with eyes opened. Functional preprocessing included distortion correction, realignment, normalization, and spatial smoothing (6mm). Using the CONN-fMRI toolbox (v21a, Whitfield-Gabrieli and Nieto-Castanon, 2012), data were band pass-filtered (0.008–0.09 Hz) and corrected for physiological noise and other artifacts by regressing out 5 spatial components from cerebrospinal fluid and white matter (without requiring global signal regression), realignment parameters and first derivatives, and individual high-motion spikes (>0.5mm or 3 standard deviations of global signal). Data were z-transformed for statistical testing. Additional details are in the supplement.

The relationships between SOR and other clinical measures (Y-BOCS, SPS, OCI-R, BAI, and QIDS-SR) were investigated using partial correlations (using site as partialing variable) corrected for false discovery rate (FDR, Benjamini and Hochberg, 1995). SOR was compared between participants with and without psychiatric medication and comorbidity using analyses-of-covariance (ANCOVAs), controlling for site.

Global connectivity was calculated as the average correlation between the time course of a given voxel and every other voxel in the brain (Whitfield-Gabrieli and Nieto-Castanon, 2012), akin to a measure of degree centrality (Cole et al., 2010) reflecting the “hubness” or interconnectedness of an area. Multiple regression examined the relationship between SOR and global connectivity using non-parametric permutation tests (10,000 permutations) with whole-brain family-wise-error-rate correction <5% (one-tailed p<0.0005 for positive and negative correlations; equivalent to two-tailed voxel wise p<0.001).

Results

See supplement for participant demographics. There was a wide range of SOR scores in our OCD sample (Figure 1A); the distribution was slightly positively skewed (skewness=0.29) but not significantly different from normal. SOR was positively correlated with clinician-rated (YBOCS) OCD symptom severity (r=0.22, p=0.02) and sensory phenomena severity (r=0.23, p=0.02) as well as self-reported (OCI-R) OCD severity (r=0.35, p<0.001), anxiety (r=0.32, p<0.001) and depression (r=0.32, p<0.001) (Figure 1B). There were no differences in SOR between participants with and without prescribed medication (p>0.2). Participants with comorbidities (estimated marginal means [EMM]=2.9) had slightly higher SOR than those without (EMM=2.6, F1,116=6.9, p=0.01).

Figure 1.

Figure 1.

Open in a new tab

A) Histogram showing the distribution of sensory over-responsivity (SOR) scores in OCD sample. Distribution was slightly skewed but not significantly different from normal (KS-test statistic=0.08, p=0.07); B) Associations between SOR scores and self-reported anxiety, depression, and obsessive-compulsive symptom severity. BAI=Beck Anxiety Inventory. QIDS=Quick Inventory of Depressive Symptomatology. OCI-R=Obsessive-Compulsive Inventory-Revised. Plotted values represent residuals with site as a covariate.

Global connectivity of an anterior medial region of orbitofrontal cortex (OFC, Brodmann’s area 11, k=154, x=14, y=62, z=−18) was positively associated with SOR scores (Figure 2). (See Supplement for follow-up seed-based connectivity analysis to “unpack” global connectivity results). OFC connectivity was not significantly related to the other clinical symptoms; however, OFC connectivity was related to OCI-R and BAI scores at trend level (r=0.21, FDR-corrected p=0.06 for both). When accounting for variance explained by these scales, SOR continued to significantly predict OFC connectivity (see supplement). OFC connectivity was not different between participants taking (EMM=−0.018) and not taking (EMM=0.075) psychiatric medications, or those with (EMM=0.017) and without (EMM=0.053) comorbidity (both F<1, p>0.5). There were no brain areas showing negative relationships with SOR.

Figure 2.

Figure 2.

Open in a new tab

OFC cluster where global connectivity was significantly related to SOR scores in OCD participants (left) and this relationship displayed as a scatterplot (right). Plotted values represent residuals with site as a covariate. OFC=orbitofrontal; SOR=sensory over-responsivity.

Discussion

A sample of 119 participants with OCD reported moderately elevated SOR on average, but meaningful variability in SOR across individuals. More severe SOR was also associated with more severe OCD symptoms, sensory phenomena, anxiety, and depression. SOR was higher in patients with comorbidities but was not impacted by concurrent usage of psychiatric medication. This pattern of results, consistent with previous findings (Dar et al., 2012; Lewin et al., 2015; Schwarzlose et al., 2023), suggests that SOR is associated with global clinical severity and may predict resistance to currently available psychotropics.

Global connectivity of anterior-medial OFC was positively related with SOR in OCD. While SOR scores were correlated with other clinical scales, these scales were not significantly related to OFC connectivity. OFC connectivity did not differ between subgroups based on either medication status or comorbidity.

OFC connectivity has been repeatedly implicated in OCD (Liu et al., 2022). The OFC encodes specific stimulus-outcome associations (stimulus value, Rudebeck and Murray, 2014), with more lateral subregions representing the sensory qualities of sensory stimuli (i.e., identity) and medial regions computing value (Rudebeck and Murray, 2014). Therefore, these findings indicate that, in OCD, SOR is associated with altered functioning of areas processing the value and consequences of sensory stimulation, which has been shown to influence behavior and subjective hedonic experience (Kringelbach, 2005).

Prior research on SOR in other populations has found inconsistent involvement of the OFC. In a small sample of autistic youth, resting-state connectivity between left OFC and the anterior insula correlated with SOR (Green et al., 2016). That study also found that SOR was positively associated with connectivity between several sensorimotor cortical regions (pre- and post-central gyri) and the anterior insula, as well as connectivity within the right amygdala, insula, and bilateral temporal poles. Resting-state connectivity of the OFC was not linked to SOR in a community sample of >11,000 adolescents in the Adolescent Brain Cognitive Development (ABCD) study (Schwarzlose et al., 2023). Instead, participants characterized as having severe SOR, when compared to those with no SOR, exhibited reduced functional connectivity within sensorimotor networks typically involved in tactile processing. Differences in sample characteristics, analytic strategies, and quantification of SOR may account for discrepancies with the current results. However, we hypothesize that connectivity differences between our findings and these prior studies may be more meaningful: while SOR symptoms in OCD may be related to an altered processing of the value of sensory stimuli, primary sensory processing abnormalities may contribute more substantially to SOR in other populations. Future investigations directly comparing SOR in distinct populations may illuminate the degree to which SOR’s neural mechanisms are transdiagnostic.

Conclusion and Limitations

This study reveals OFC connectivity as a neural mechanism of SOR in OCD. Future investigations should explore neural responses to sensory stimulation tasks in OCD and compare findings with those obtained in other conditions also characterized by high SOR such as autism spectrum disorder (Green et al., 2015). With replication and extension, the present findings may ultimately be used to develop and refine OCD treatments, particularly for those with elevated SOR, and illuminate the pathophysiology of SOR transdiagnostically.

Supplementary Material

1

Highlights.

OFC connectivity implicated in sensory over-responsivity in OCD.

Neural mechanisms of sensory over-responsivity in OCD illuminated.

Brain and clinical correlates distinguish sensory over-responsivity from other symptoms in OCD.

Funding:

This work was supported by National Institutes of Health (R01MH111794, R21/33MH107589, and R01MH126981).

Footnotes

Declaration of Interests: Dr. Collins has consulted for MedAvante-ProPhase, and A. Stein- Regulatory Affairs Consulting, Ltd. in the past, and currently serves as a consultant to Cronos Clinical Consulting Services, Inc. and Relmada Therapeutics, Inc. Dr. Tobe has received grant support from Axial Therapeutics; F. Hoffmann-La Roche Ltd; Janssen Research & Development, LLC; and MapLight Therapeutics, Inc. Dr. Tobe has also attended advisory boards for F. Hoffmann-La Roche Ltd. Dr. Eng, Dr. Stern, Ms. Recchia and Ms. Harvey report no financial relationships with commercial interests.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

References:

  1. American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders: DSM-5, 5th ed. ed. American Psychiatric Association, Arlington, VA. [Google Scholar]
  2. Beck AT, Epstein N, Brown G, Steer RA, 1988. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56, 893–897. 10.1037//0022-006x.56.6.893 [DOI] [PubMed] [Google Scholar]
  3. Benjamini Y, Hochberg Y, 1995. Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological) 57, 289–300. 10.1111/j.2517-6161.1995.tb02031.x [DOI] [Google Scholar]
  4. Brown C, Dunn W, 2002. Adolescent-Adult Sensory Profile: User’s manual. Therapy Skill Builders: Psychological Corp., San Antonio, Tex. [Google Scholar]
  5. Brown C, Shahab R, Collins K, Fleysher L, Goodman WK, Burdick KE, Stern ER, 2019. Functional neural mechanisms of sensory phenomena in obsessive-compulsive disorder. J Psychiatr Res 109, 68–75. 10.1016/j.jpsychires.2018.11.018 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown C, Tollefson N, Dunn W, Cromwell R, Filion D, 2001. The Adult Sensory Profile: measuring patterns of sensory processing. Am J Occup Ther 55, 75–82. 10.5014/ajot.55.1.75 [DOI] [PubMed] [Google Scholar]
  7. Cole MW, Pathak S, Schneider W, 2010. Identifying the brain’s most globally connected regions. Neuroimage 49, 3132–3148. 10.1016/j.neuroimage.2009.11.001 [DOI] [PubMed] [Google Scholar]
  8. Dar R, Kahn DT, Carmeli R, 2012. The relationship between sensory processing, childhood rituals and obsessive–compulsive symptoms. Journal of Behavior Therapy and Experimental Psychiatry 43, 679–684. 10.1016/j.jbtep.2011.09.008 [DOI] [PubMed] [Google Scholar]
  9. Eng GK, Collins KA, Brown C, Ludlow M, Tobe RH, Iosifescu DV, Stern ER, 2022. Relationships between interoceptive sensibility and resting-state functional connectivity of the insula in obsessive-compulsive disorder. Cereb Cortex 32, 5285–5300. 10.1093/cercor/bhac014 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eng GK, Collins KA, Brown C, Ludlow M, Tobe RH, Iosifescu DV, Stern ER, 2020. Dimensions of interoception in obsessive-compulsive disorder. J Obsessive Compuls Relat Disord 27. 10.1016/j.jocrd.2020.100584 [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foa EB, Huppert JD, Leiberg S, Langner R, Kichic R, Hajcak G, Salkovskis PM, 2002. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 14, 485–496. [PubMed] [Google Scholar]
  12. Glover GH, Mueller BA, Turner JA, van Erp TGM, Liu TT, Greve DN, Voyvodic JT, Rasmussen J, Brown GG, Keator DB, Calhoun VD, Lee HJ, Ford JM, Mathalon DH, Diaz M, O’Leary DS, Gadde S, Preda A, Lim KO, Wible CG, Stern HS, Belger A, McCarthy G, Ozyurt B, Potkin SG, 2012. Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies. J Magn Reson Imaging 36, 39–54. 10.1002/jmri.23572 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS, 1989. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 46, 1006–1011. 10.1001/archpsyc.1989.01810110048007 [DOI] [PubMed] [Google Scholar]
  14. Green SA, Hernandez L, Bookheimer SY, Dapretto M, 2016. Salience network connectivity in Autism is related to brain and behavioral markers of sensory over-responsivity. J Am Acad Child Adolesc Psychiatry 55, 618–626.e1. 10.1016/j.jaac.2016.04.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Green SA, Hernandez L, Tottenham N, Krasileva K, Bookheimer SY, Dapretto M, 2015. Neurobiology of sensory overresponsivity in youth with Autism spectrum disorders. JAMA Psychiatry 72, 778–786. 10.1001/jamapsychiatry.2015.0737 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kringelbach ML, 2005. The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci 6, 691–702. 10.1038/nrn1747 [DOI] [PubMed] [Google Scholar]
  17. Lewin AB, Wu MS, Murphy TK, Storch EA, 2015. Sensory Over-Responsivity in Pediatric Obsessive Compulsive Disorder. J Psychopathol Behav Assess 37, 134–143. 10.1007/s10862-014-9442-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liu J, Cao L, Li H, Gao Y, Bu X, Liang K, Bao W, Zhang S, Qiu H, Li X, Hu Xinyue, Lu L., Zhang L., Hu Xinyu, Huang X., Gong Q., 2022. Abnormal resting-state functional connectivity in patients with obsessive-compulsive disorder: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews 135, 104574. 10.1016/j.neubiorev.2022.104574 [DOI] [PubMed] [Google Scholar]
  19. Miller LJ, Anzalone ME, Lane SJ, Cermak SA, Osten ET, 2007. Concept evolution in sensory integration: A proposed nosology for diagnosis 61, 7. [DOI] [PubMed] [Google Scholar]
  20. Rosario MC, Prado HS, Borcato S, Diniz JB, Shavitt RG, Hounie AG, Mathis ME, Mastrorosa RS, Velloso P, Perin EA, Fossaluza V, Pereira CA, Geller D, Leckman J, Miguel E, 2009. Validation of the University of São Paulo Sensory Phenomena Scale: Initial psychometric properties. CNS Spectr 14, 315–323. 10.1017/s1092852900020319 [DOI] [PubMed] [Google Scholar]
  21. Rudebeck PH, Murray EA, 2014. The orbitofrontal oracle: cortical mechanisms for the prediction and evaluation of specific behavioral outcomes. Neuron 84, 1143–1156. 10.1016/j.neuron.2014.10.049 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB, 2003. The 16-Item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54, 573–583. 10.1016/S0006-3223(02)01866-8 [DOI] [PubMed] [Google Scholar]
  23. Schwarzlose RF, Tillman R, Hoyniak CP, Luby JL, Barch DM, 2023. Sensory over-responsivity: A feature of childhood psychiatric illness associated with altered functional connectivity of sensory networks. Biological Psychiatry, Genetics and Neurodevelopment In Psychiatry 93, 92–101. 10.1016/j.biopsych.2022.09.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stern ER, Brown C, Ludlow M, Shahab R, Collins K, Lieval A, Tobe RH, Iosifescu DV, Burdick KE, Fleysher L, 2020. The buildup of an urge in obsessive-compulsive disorder: Behavioral and neuroimaging correlates. Hum Brain Mapp. 10.1002/hbm.24898 [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stern ER, Eng GK, De Nadai AS, Iosifescu DV, Tobe RH, Collins KA, 2022. Imbalance between default mode and sensorimotor connectivity is associated with perseverative thinking in obsessive-compulsive disorder. Transl Psychiatry 12, 19. 10.1038/s41398-022-01780-w [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Whitfield-Gabrieli S, Nieto-Castanon A, 2012. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2, 125–141. 10.1089/brain.2012.0073 [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

1
NIHMS1972674-supplement-1.docx (159.5KB, docx)

RESOURCES