Darren L Clark1, Kara A Johnson2, Christopher R Butson3, Catherine Lebel4, David Gobbi5, Rajamannar Ramasubbu1, Zelma H T Kiss6. 1. Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. 2. Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA. 3. Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Departments of Neurology, Neurosurgery, and Psychiatry, University of Utah, Salt Lake City, UT, USA. 4. Department of Radiology, University of Calgary, Calgary, AB, Canada; Child and Adolescent Imaging Research Program, Alberta Children's Hosspital, Calgary, AB, Canada. 5. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada. 6. Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address: zkiss@ucalgary.ca.
Abstract
BACKGROUND: Deep brain stimulation (DBS) of subcallosal cingulate cortex (SCC) is a promising investigational therapy for treatment-resistant depression (TRD). However, outcomes vary, likely due to suboptimal DBS placement. Ideal placement is proposed to stimulate 4 SCC white matter bundles; however, no quantitative data have linked activation of these target tracts to response. OBJECTIVE: Here we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response. METHODS: DTI was performed in 19 TRD patients who received SCC-DBS. We defined clinical response as >48% reduction from baseline in the Hamilton Depression Rating Scale. Bilateral VTAs were generated based on subject-specific stimulation parameters. Patient-specific tract maps emanating from the VTAs were calculated using whole-brain probabilistic DTI. The four target tracts were isolated using tract-specific quantification and examined for overlap with DBS activated tissue. RESULTS: Medial frontal and temporal projections were stimulated in all responders at 6 and 12 months. Individual tract-based generalized linear mixed model analysis revealed a significant tract-by-response interaction at both 6 (F(1,135) = 3.828, p = 0.001) and 12 (F(1,135) = 5.688, p < 0.001) months, with post hoc tests revealing a response-related increase in cingulum activation at 6 months (t(135) = 2.418, p = 0.017) and decrease in forceps minor activation at 12 months (t(135) = -2.802, p = 0.006). CONCLUSIONS: A wider profile of white matter tracts, particularly to the medial frontal, was associated with DBS response. Cingulum bundle stimulation may promote early response and excess stimulation of the forceps minor might be detrimental. Our work supports prospective patient-specific targeting to inform personalized DBS.
BACKGROUND: Deep brain stimulation (DBS) of subcallosal cingulate cortex (SCC) is a promising investigational therapy for treatment-resistant depression (TRD). However, outcomes vary, likely due to suboptimal DBS placement. Ideal placement is proposed to stimulate 4 SCC white matter bundles; however, no quantitative data have linked activation of these target tracts to response. OBJECTIVE: Here we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response. METHODS: DTI was performed in 19 TRD patients who received SCC-DBS. We defined clinical response as >48% reduction from baseline in the Hamilton Depression Rating Scale. Bilateral VTAs were generated based on subject-specific stimulation parameters. Patient-specific tract maps emanating from the VTAs were calculated using whole-brain probabilistic DTI. The four target tracts were isolated using tract-specific quantification and examined for overlap with DBS activated tissue. RESULTS: Medial frontal and temporal projections were stimulated in all responders at 6 and 12 months. Individual tract-based generalized linear mixed model analysis revealed a significant tract-by-response interaction at both 6 (F(1,135) = 3.828, p = 0.001) and 12 (F(1,135) = 5.688, p < 0.001) months, with post hoc tests revealing a response-related increase in cingulum activation at 6 months (t(135) = 2.418, p = 0.017) and decrease in forceps minor activation at 12 months (t(135) = -2.802, p = 0.006). CONCLUSIONS: A wider profile of white matter tracts, particularly to the medial frontal, was associated with DBS response. Cingulum bundle stimulation may promote early response and excess stimulation of the forceps minor might be detrimental. Our work supports prospective patient-specific targeting to inform personalized DBS.
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