TY - JOUR
T1 - Individualized connectome-targeted transcranial magnetic stimulation for neuropsychiatric sequelae of repetitive traumatic brain injury in a retired NFL player
AU - Siddiqi, Shan H.
AU - Trapp, Nicholas T.
AU - Shahim, Pashtun
AU - Hacker, Carl D.
AU - Laumann, Timothy O.
AU - Kandala, Sridhar
AU - Carter, Alexandre R.
AU - Brody, David L.
N1 - Funding Information:
The Departments of Psychiatry, Neurology, and Neurosurgery, Washington University School of Medicine, St. Louis (Siddiqi, Trapp, Laumann, Kandala, Shahim, Carter, Brody, Hacker); and Department of Neurology, Harvard Medical School, McLean Hospital, Boston (Siddiqi); and the Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi, Shahim); and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa (Trapp). Send correspondence to Dr. Siddiqi (shan.siddiqi@mgh.harvard.edu). The authors have confirmed that details of the case have been disguised to protect patient privacy. Supported by pilot funds from the McDonnell Center for Systems Neuroscience and the Mallinckrodt Institute of Radiology at Washington University, St. Louis. Data were provided in part by the Human Connectome Project, Washington University-University of Minnesota Consortium (principal investigators, David Van Essen, Ph.D., and Kamil Ugurbil, Ph.D. [1U54MH091657]), funded by NIH, and the McDonnell Center for Systems Neuroscience at Washington University. The authors thank the experimental participant and the participants in the comparator groups. The authors also thank Drs. Eric Leuthardt and Abraham Snyder for logistical support with implementation of individualized RSN mapping; Xin Hong and Linda Hood for technical support with rTMS and MRI equipment; Drs. Sindhu Jacob and Martin Wice for referring participants; Drs. Bradley Schlaggar, Charles Zor-umski, and David Soleimani-Meigooni for editorial support; Drs. Michael Fox, Steven Petersen, Charles Conway, Eric Wasserman, Sarah Lisanby, Bruce Luber, Andrew Drysdale, Irving Reti, Vani Rao, Maurizio Corbetta, Gordon Shulman, and Abraham Snyder for assistance with the conception and refinement of the study design; and Drs. Kevin Black, Pilar Cristancho, Charles Zorumski, and C. Robert Cloninger for extensive longitudinal guidance. ClinicalTrials.gov, NCT02980484. Dr. Siddiqi serves as a scientific consultant to SigNEURO LLC. Dr. Brody has served as a consultant to Avid Radiopharmaceuticals (Eli Lilly), GLG, Intellectual Ventures, iPerian, Kypha, Pfizer, Sage Therapeutics, Signum Nutralogix, the St. Louis County Medical Examiner, the St. Louis County Public Defender, Stemedica, and the United States Attorney’s Office. All other authors report no financial relationships with commercial interests. Received October 16, 2018; revision received November 6, 2018; accepted December 12, 2018; published online April 3, 2019.
Publisher Copyright:
© 2019, American Psychiatric Association. All rights reserved.
PY - 2019/7
Y1 - 2019/7
N2 - Objective: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial inter-individual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC). Personalized rTMS may be particularly useful after repetitive traumatic brain injury (TBI), which is associated with neurodegenerative tauo-pathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes. Methods: The authors describe a case in which RSNM was successfully used to target rTMS to treat these neuropsychiatric disturbances in a retired NFL defensive lineman whose symptoms were not responsive to conventional treatments. RSNM was used to identify left-right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and DMN correlations. These targets were spatially distinct from those identified by prior methods. Twenty sessions of left-sided excitatory and right-sided inhibitory rTMS were administered at these targets. Results: Treatment led to improvement in Montgomery-Åsberg Depression Rating Scale (72%), cognitive testing, and headache scales scores. Compared with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with the medial temporal lobe (MTL). Serial rsfMRI scans revealed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with sgACC. Conclusions: These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.
AB - Objective: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial inter-individual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC). Personalized rTMS may be particularly useful after repetitive traumatic brain injury (TBI), which is associated with neurodegenerative tauo-pathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes. Methods: The authors describe a case in which RSNM was successfully used to target rTMS to treat these neuropsychiatric disturbances in a retired NFL defensive lineman whose symptoms were not responsive to conventional treatments. RSNM was used to identify left-right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and DMN correlations. These targets were spatially distinct from those identified by prior methods. Twenty sessions of left-sided excitatory and right-sided inhibitory rTMS were administered at these targets. Results: Treatment led to improvement in Montgomery-Åsberg Depression Rating Scale (72%), cognitive testing, and headache scales scores. Compared with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with the medial temporal lobe (MTL). Serial rsfMRI scans revealed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with sgACC. Conclusions: These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.
UR - http://www.scopus.com/inward/record.url?scp=85070180154&partnerID=8YFLogxK
U2 - 10.1176/appi.neuropsych.18100230
DO - 10.1176/appi.neuropsych.18100230
M3 - Article
C2 - 30945588
AN - SCOPUS:85070180154
VL - 31
SP - 254
EP - 263
JO - Journal of Neuropsychiatry and Clinical Neurosciences
JF - Journal of Neuropsychiatry and Clinical Neurosciences
SN - 0895-0172
IS - 3
ER -