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Research Article: Altered anterior cingulate cortex functional connectivity in treatment-naïve obsessive-compulsive disorder: a resting-state fMRI study

Date Published: 2026-05-26

Abstract:
To investigate the anterior cingulate cortex (ACC) resting-state functional connectivity patterns in OCD patients who have not yet received therapy and analyze how they relate to the intensity of their clinical symptoms. Resting-state fMRI data were acquired from 46 medication-naïve participants with OCD and 33 demographically comparable neurotypical control subjects. The region of focus for the seed-based whole-brain functional connectivity investigation was bilateral ACC. Relationships between aberrant connections and clinical characteristics measured by the Y-BOCS, HAMD-17, and HAMA were investigated using Pearson’s correlation coefficient and partial correlation analysis. Key findings (OCD patients vs. healthy controls): Increased functional connectivity (FC) in OCD patients: Right insula (Brodmann area 48), Right hippocampus (BA 20), Right fusiform gyrus (BA 37); Decreased FC involving the anterior cingulate cortex (ACC) with: Right supplementary motor area (SMA, BA 32), Left inferior frontal gyrus (IFG, BA 47) (AlphaSim corrected, P < 0.05). Clinical association: There was a significant positive relationship between Y-BOCS total scores (a measure of OCD symptom severity) and FC strength linking the left IFG to the ACC (r = 0.351, P = 0.017). In practical terms, greater symptom severity is associated with stronger coupling between these two regions. No other clear brain-behavior relationships were found in the other regions examined. Treatment-naïve OCD patients demonstrate distinct ACC functional connectivity alterations involving cognitive control, motor planning, and limbic processing regions. The specific association between left inferior frontal gyrus (IFG)-ACC connectivity and symptom severity suggests that this pathway may serve as a neurobiological marker for OCD pathophysiology.

Introduction:
About 2–3% of the worldwide population is affected by obsessive-compulsive disorder (OCD), a persistent and debilitating mental illness characterized by unwanted obsessive thoughts and recurrent compulsive behaviors or mental acts ( 1 , 2 ). The disorder typically emerges in adolescence or early adulthood and imposes substantial functional impairment and a reduced quality of life on affected individuals ( 3 ). Converging evidence from neuroimaging research over the last three decades has linked a key…

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