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Abstract Details

TMS Targets for Multiple Sclerosis Related Depression Derived Using a Precomputed Functional Connectome
Multiple Sclerosis
P11 - Poster Session 11 (11:45 AM-12:45 PM)
3-014

Deriving TMS targets for multiple sclerosis related depression using a precomputed functional connectome.
Depression in multiple sclerosis (MS) is poorly responsive to conventional pharmacotherapy, highlighting the need for clinical TMS trials. However, it is unclear if MS depression is suitable for circuit-targeted therapeutics. We developed a technique for identifying treatment targets based on distributed brain circuits derived from symptom-causing brain lesions. We tested this technique using published maps that define circuits connected to lesions associated with greater depression and that have been shown to predict TMS outcomes.

We analyzed a recently-published “MS depression circuit map” based on the normative connectivity of brain lesions that increase risk of depression in MS (Siddiqi et al., Nature Mental Health 2023). We constructed a precomputed functional connectome using mean whole-brain functional connectivity of 292,019 brain voxels across 1,000 participants. We compared each voxel’s connectivity map to the MS depression circuit map using spatial correlations. Voxels whose connectivity maps most correlate with the MS depression circuit map are identified as potential TMS targets. As a comparator, we conducted the same analysis using a published depression circuit map derived from stroke lesions and penetrating head trauma (N=461), which has been shown to reveal better TMS targets (Siddiqi et al., Nature Human Behaviour 2021).

The peak lesion-derived TMS target for MS depression was at MNI coordinates (-38,44,34). This target was within 1cm of the TMS target derived from other lesion types located at (-44,38,30) and a previous TMS target derived from subgenual cingulate anti-correlations at (-42,44,30).

The precomputed functional connectome is a high-resolution atlas of voxel-wise functional connectivity that reveals potential therapeutic neuromodulation targets by comparing their connectivity to a template brain map. Our proposed TMS target for MS depression is near the current clinical TMS targets for depression, suggesting that MS depression may respond to TMS.
Authors/Disclosures
William Drew (Brigham and Women's Hospital)
PRESENTER 		Mr. Drew has nothing to disclose.
Isaiah Kletenik, MD (BRIGHAM AND WOMEN’S HOSPITAL) The institution of Dr. Kletenik has received research support from NIH.
Rohit Bakshi, MD, FAAN Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.
Michele Cavallari, MD (Brigham and Woman's Hospital) The institution of Dr. Cavallari has received research support from BrightFocus Foundation. The institution of Dr. Cavallari has received research support from Brigham Research Institute. The institution of Dr. Cavallari has received research support from Department of Radiology at Brigham and Women's Hospital. The institution of Dr. Cavallari has received research support from Hebrew SeniorLife Rehabilitation Center. Dr. Cavallari has received intellectual property interests from a discovery or technology relating to health care.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital) Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Bonnie Glanz (Brigham and Women'S Hospital) The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
Charles R. Guttmann Charles R.G. Guttmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sintetica SA. Charles R.G. Guttmann has received stock or an ownership interest from Alnylam. Charles R.G. Guttmann has received stock or an ownership interest from Roche. Charles R.G. Guttmann has received stock or an ownership interest from Novartis. Charles R.G. Guttmann has received stock or an ownership interest from Arrowhead Pharmaceuticals. Charles R.G. Guttmann has received stock or an ownership interest from Protalix. Charles R.G. Guttmann has received stock or an ownership interest from Promethee. Charles R.G. Guttmann has received stock or an ownership interest from GSK. Charles R.G. Guttmann has received stock or an ownership interest from Sangamo. Charles R.G. Guttmann has received stock or an ownership interest from Alcon. Charles R.G. Guttmann has received stock or an ownership interest from Cocrystal Pharma. The institution of Charles R.G. Guttmann has received research support from NIH. The institution of Charles R.G. Guttmann has received research support from McGill University. The institution of Charles R.G. Guttmann has received research support from National Multiple Sclerosis Society. The institution of Charles R.G. Guttmann has received research support from BrightFocus Foundation. The institution of Charles R.G. Guttmann has received research support from National Multiple Sclerosis Society. The institution of Charles R.G. Guttmann has received research support from University of Connecticut Health Center. The institution of Charles R.G. Guttmann has received research support from U.S. Office of Naval Research.
No disclosure on file
Michael D. Fox, MD, PhD (Brigham and Women's Hospital / Harvard Medical School) Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley.
Shan Siddiqi, MD (Washington University in St. Louis) Dr. Siddiqi has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Magnus Medical. Dr. Siddiqi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Brainsway Ltd. Dr. Siddiqi has stock in Brainsway Ltd. Dr. Siddiqi has stock in Magnus Medical. Dr. Siddiqi has received intellectual property interests from a discovery or technology relating to health care.