Michael Avissar1, Fon Powell2, Irena Ilieva3, Matteo Respino4, Faith M Gunning3, Conor Liston5, Marc J Dubin6. 1. Division of Experimental Therapeutics, New York State Psychiatric Institute/Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA. 2. Department of Radiology, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA. 3. Department of Psychiatry, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA; Institute of Geriatric Psychiatry, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA. 4. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy. 5. Department of Psychiatry, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA; Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA. 6. Department of Psychiatry, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College-New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA. Electronic address: mrd9035@med.cornell.edu.
Abstract
BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a non-invasive, safe, and efficacious treatment for depression. TMS has been shown to normalize abnormal functional connectivity of cortico-cortical circuits in depression and baseline functional connectivity of these circuits predicts treatment response. Less is known about the relationship between functional connectivity of frontostriatal circuits and treatment response. OBJECTIVE/HYPOTHESIS: We investigated whether baseline functional connectivity of distinct frontostriatal circuits predicted response to TMS. METHODS: Resting-state fMRI (rsfMRI) was acquired in 27 currently depressed subjects with treatment resistant depression and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional connectivity between limbic, executive, rostral motor, and caudal motor regions of frontal cortex and their corresponding striatal targets were determined at baseline using an existing atlas based on diffusion tensor imaging. TMS treatment response was measured by percent reduction in the 24-item Hamilton Depression Rating Scale (HAMD24). In an exploratory analysis, correlations were determined between baseline functional connectivity and TMS treatment response. RESULTS: Seven cortical clusters belonging to the executive and rostral motor frontostriatal projections had reduced functional connectivity in depression compared to healthy controls. No frontostriatal projections showed increased functional connectivity in depression (voxel-wise p < 0.01, family-wise α < 0.01). Only baseline functional connectivity between the left DLPFC and the striatum predicted TMS response. Higher baseline functional connectivity correlated with greater reductions in HAMD24 (Pearson's R = 0.58, p = 0.002). CONCLUSION(S): In an exploratory analysis, higher functional connectivity between the left DLPFC and striatum predicted better treatment response. Our findings suggest that the antidepressant mechanism of action of TMS may require connectivity from cortex proximal to the stimulation site to the striatum.
BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a non-invasive, safe, and efficacious treatment for depression. TMS has been shown to normalize abnormal functional connectivity of cortico-cortical circuits in depression and baseline functional connectivity of these circuits predicts treatment response. Less is known about the relationship between functional connectivity of frontostriatal circuits and treatment response. OBJECTIVE/HYPOTHESIS: We investigated whether baseline functional connectivity of distinct frontostriatal circuits predicted response to TMS. METHODS: Resting-state fMRI (rsfMRI) was acquired in 27 currently depressed subjects with treatment resistant depression and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional connectivity between limbic, executive, rostral motor, and caudal motor regions of frontal cortex and their corresponding striatal targets were determined at baseline using an existing atlas based on diffusion tensor imaging. TMS treatment response was measured by percent reduction in the 24-item Hamilton Depression Rating Scale (HAMD24). In an exploratory analysis, correlations were determined between baseline functional connectivity and TMS treatment response. RESULTS: Seven cortical clusters belonging to the executive and rostral motor frontostriatal projections had reduced functional connectivity in depression compared to healthy controls. No frontostriatal projections showed increased functional connectivity in depression (voxel-wise p < 0.01, family-wise α < 0.01). Only baseline functional connectivity between the left DLPFC and the striatum predicted TMS response. Higher baseline functional connectivity correlated with greater reductions in HAMD24 (Pearson's R = 0.58, p = 0.002). CONCLUSION(S): In an exploratory analysis, higher functional connectivity between the left DLPFC and striatum predicted better treatment response. Our findings suggest that the antidepressant mechanism of action of TMS may require connectivity from cortex proximal to the stimulation site to the striatum.
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