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White Matter Integrity Correlates with Strength of Response to Deep Brain Stimulation in Treatment-Resistant Obsessive-Compulsive Disorder

Nitcheu, G. L. T.; El Jammal, R.; Suzuki, H.; Soubra, S.; Hamre, T. A.; Ryan, M. A.; Chamarthi, S.; Belavadi, V.; Perry, Z.; Kutcher, T.; Gates, V.; Banks, G. P.; Vanegas Arroyave, N.; Storch, E. A.; Goodman, W. K.; Sheth, S. A.; Heilbronner, S. R.; Provenza, N. R.

2026-05-13 psychiatry and clinical psychology
10.64898/2026.05.11.26352565 medRxiv
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BackgroundDeep brain stimulation (DBS) is effective for approximately two-thirds of patients with treatment-resistant obsessive-compulsive disorder (OCD). While prior work has emphasized the engagement of specific white matter tracts in mediating outcomes, the contribution of region-specific white matter integrity to clinical response remains unclear. MethodsTwelve patients with treatment-resistant OCD underwent preoperative neuroimaging and DBS at our center. We assessed OCD severity preoperatively and at [~]18 months postoperatively. We extracted mean fractional anisotropy (FA) for the anterior limb of the internal capsule (ALIC) and a control tract and used Spearmans rank correlations to evaluate associations between FA and symptom improvement. We additionally evaluated this relationship for 49 white matter bundles. Finally, we used diffusion tractography to determine endpoints connected with ALIC voxels most predictive of symptom improvement. ResultsHigher preoperative ALIC FA was associated with greater clinical improvement following DBS (p=0.002). This effect was specific to the ALIC and not the control tract. Hemispheric asymmetry (right>left) in ALIC FA was moderately correlated with clinical improvement. Among all 49 bundles, the right ALIC demonstrated the strongest association with clinical improvement. Streamlines passing through the ALIC voxels that most strongly correlated with outcome ended in the diencephalon and superior frontal cortex. ConclusionsBaseline structural integrity of the ALIC was associated with the magnitude of clinical improvement following DBS for OCD. These findings suggest that regional variation in white matter integrity may reflect an underlying circuit disruption amenable to DBS, supporting the use of neuroimaging-based metrics as potential biomarkers in DBS treatment.

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