Resting fMRI-guided TMS evokes subgenual anterior cingulate response in depression
Romain J. Duprat,
Kristin A. Linn,
Theodore D. Satterthwaite,
Yvette I. Sheline,
Ximo Liang,
Gabriela Bagdon,
Matthew W. Flounders,
Heather Robinson,
Michael Platt,
Joseph Kable,
Hannah Long,
Morgan Scully,
Joseph A. Deluisi,
Michael Thase,
Mario Cristancho,
Julie Grier,
Camille Blaine,
Almaris Figueroa-González,
Desmond J. Oathes
Affiliations
Romain J. Duprat
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Kristin A. Linn
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, Philadelphia, PA, USA; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; The Penn Statistics in Imaging and Visualization Endeavor, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, Philadelphia, PA, USA
Theodore D. Satterthwaite
University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA; Penn Lifespan Informatics and Neuroimaging Center, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Yvette I. Sheline
Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Ximo Liang
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Gabriela Bagdon
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Matthew W. Flounders
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Heather Robinson
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Michael Platt
University of Pennsylvania, Department of Psychology, Philadelphia, PA, USA; University of Pennsylvania, Department of Neuroscience, Philadelphia, PA, USA; University of Pennsylvania, Department of Marketing, Philadelphia, PA, USA
Joseph Kable
University of Pennsylvania, Department of Psychology, Philadelphia, PA, USA
Hannah Long
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Morgan Scully
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Joseph A. Deluisi
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Michael Thase
University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Mario Cristancho
University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Julie Grier
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Camille Blaine
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Almaris Figueroa-González
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA
Desmond J. Oathes
Center for Brain Imaging and Stimulation, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, USA; Center for the Neuromodulation of Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA; University of Pennsylvania, Penn Brain Science, Translation, Innovation, and Modulation Center, Philadelphia, PA, USA; Corresponding author at: Richards Biomedical Building, D306, 3700 Hamilton Walk, Philadelphia, PA 19104, USA.
Background: Depression alleviation following treatment with repetitive transcranial magnetic stimulation (rTMS) tends to be more effective when TMS is targeted to cortical areas with high (negative) resting state functional connectivity (rsFC) with the subgenual anterior cingulate cortex (sgACC). However, the relationship between sgACC-cortex rsFC and the TMS-evoked response in the sgACC is still being explored and has not yet been established in depressed patients. Objectives: In this study, we investigated the relationship between sgACC-cortical (site of stimulation) rsFC and induced evoked responses in the sgACC in healthy controls and depressed patients. Methods: For each participant (N = 115, 34 depressed patients), a peak rsFC cortical ‘hotspot’ for the sgACC and control targets were identified at baseline. Single pulses of TMS interleaved with fMRI readouts were administered to these targets to evoke downstream fMRI blood-oxygen-level-dependent (BOLD) responses in the sgACC. Generalized estimating equations were used to investigate the association between TMS-evoked BOLD responses in the sgACC and rsFC between the stimulation site and the sgACC. Results: Stimulations over cortical sites with high rsFC to the sgACC were effective in modulating activity in the sgACC in both healthy controls and depressed patients. Moreover, we found that in depressed patients, sgACC rsFC at the site of stimulation was associated with the induced evoked response amplitude in the sgACC: stronger positive rsFC values leading to stronger evoked responses in the sgACC. Conclusions: rsFC-based targeting is a viable strategy to causally modulate the sgACC. Assuming an anti-depressive mechanism working through modulation of the sgACC, the field's exclusive focus on sites anticorrelated with the sgACC for treating depression should be broadened to explore positively-connected sites.
