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Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD)

Abstract

Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.

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Acknowledgments

The authors would also like to acknowledge Dr. Jonathan Polimeni and Dr. Emad Ahmadi for assisting with acquisition of postmortem material MRI data.

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Correspondence to Nikolaos Makris.

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Funding

This study was supported, in part, by grants from: NIH, NIBIB R21EB016449 (NM and GB); from NIH, 5 UO1 MH 093765-05 (LW, QF and AN); from NIMH, RO1MH097979 (YR); from NIMH, R01 MH102377 (MK and NM); from Colby College Research Fund 01 2836 (EY); from Medtronic, Cyberonics, Roche and Eli Lilly and Company (DD).

Conflicts of interest

Nikolaos Makris, Yogesh Rathi, Palig Mouradian, Giorgio Bonmassar, George Papadimitriou, Wingkwai I. Ing, Edward H. Yeterian, Marek Kubicki, Lawrence Wald, Qiuyun Fan, Aapo Nummenmaa declare that they have no conflict of interest. Darin D. Dougherty has receivedspeaker honoraria from Insys and Johnson & Johnson, and has received research grants from Medtronic, Cyberonics, Roche and Eli Lilly. Alik S. Widge, Darin Dougherty and Emad N. Eskandar are named inventors on patents related to improved targeting and delivery of deep brain stimulation.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients included in the study.

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Makris, N., Rathi, Y., Mouradian, P. et al. Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD). Brain Imaging and Behavior 10, 1054–1067 (2016). https://doi.org/10.1007/s11682-015-9462-9

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Keywords

  • Diffusion tensor imaging
  • Diffusion tractography
  • Connectome
  • Obsessive-compulsive disorder (OCD)
  • Deep brain stimulation (DBS)
  • Tractography-guided DBS