• Shan H Siddiqi, Nicholas T Trapp, Pashtun Shahim, Carl D Hacker, Timothy O Laumann, Sridhar Kandala, Alexandre R Carter, and David L Brody.
• 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).
• J Neuropsychiatry Clin Neurosci. 2019 Jan 1; 31 (3): 254-263.

ObjectiveThe recent advent of individualized resting-state network mapping (RSNM) has revealed substantial interindividual 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 tauopathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes.MethodsThe 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.ResultsTreatment 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.ConclusionsThese results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

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