White matter integrity and functional predictors of response to repetitive transcranial magnetic stimulation for posttraumatic stress disorder and major depression
Corresponding Author
Jennifer Barredo
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Correspondence Jennifer Barredo, PhD, Providence VA Medical Center 830 Chalkstone Ave, Bldg. 32 Providence, RI 02908.
Email: [email protected]
Search for more papers by this authorJohn A. Bellone
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Search for more papers by this authorMelissa Edwards
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Search for more papers by this authorLinda L. Carpenter
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorStephen Correia
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorNoah S. Philip
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorCorresponding Author
Jennifer Barredo
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Correspondence Jennifer Barredo, PhD, Providence VA Medical Center 830 Chalkstone Ave, Bldg. 32 Providence, RI 02908.
Email: [email protected]
Search for more papers by this authorJohn A. Bellone
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Search for more papers by this authorMelissa Edwards
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Search for more papers by this authorLinda L. Carpenter
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorStephen Correia
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorNoah S. Philip
Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, Rhode Island
Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, Rhode Island
Butler Hospital Neuromodulation Research Facility, Providence, Rhode Island
Search for more papers by this authorAbstract
Background
Recent evidence suggests that therapeutic repetitive transcranial magnetic stimulation (TMS) is an effective treatment for pharmacoresistant posttraumatic stress disorder (PTSD) and comorbid major depressive disorder (MDD). We recently demonstrated that response to 5 Hz TMS administered to the dorsolateral prefrontal cortex was predicted by functional connectivity of the medial prefrontal (MPFC) and subgenual anterior cingulate cortex (sgACC). This functionally-defined circuit is a novel target for treatment optimization research, however, our limited knowledge of the structural pathways that underlie this functional predisposition is a barrier to target engagement research.
Methods
To investigate underlying structural elements of our previous functional connectivity findings, we submitted pre-TMS diffusion-weighted imaging data from 20 patients with PTSD and MDD to anatomically constrained tract-based probabilistic tractography (FreeSurfer's TRActs Constrained by UnderLying Anatomy). Averaged pathway fractional anisotropy (FA) was extracted from four frontal white matter tracts: the forceps minor, cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculi. Tract FA statistics were treated as explanatory variables in backward regressions testing the relationship between tract integrity and functional connectivity coefficients from MPFC and sgACC predictors of symptom improvement after TMS.
Results
FA in the ATRs was consistently associated with symptom improvement in PTSD and MDD (Bonferroni-corrected p < .05).
Conclusion
We found that structural characteristics of the ATR account for significant variance in individual-level functional predictors of post-TMS improvement. TMS optimization studies should target this circuit either in stand-alone or successive TMS stimulation protocols.
CONFLICT OF INTERESTS
Dr. Barredo reports grants from Veterans Affairs Clinical Science Research and Development (1IK2CX001824-01A1) and Veterans Affairs Rehabilitation Research and Development (1I50RX002864-01) during the conduct of the study. Dr Carpenter reports an investigator-initiated grant from Neuronetics supporting the conduct of the study; personal fees for consulting from Magstim, research equipment support from Nexstim, grants from Feelmore Labs, grants and personal fees for consulting from Janssen, grants from Neosync, and research equipment from Neuronetics, outside the submitted work. This study was funded in part by an investigator-initiated grant from Neuronetics, Inc. to Butler Hospital (Dr Carpenter and Dr Philip). Dr Philip has also received grant support from Neosync and Janssen through clinical trial contracts and has been an unpaid scientific advisory board member for Neuronetics.
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