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J Neurotrauma. 2018 Nov 1. doi: 10.1089/neu.2018.5889. [Epub ahead of print]

Repetitive Transcranial Magnetic Stimulation with Resting State Network Targeting for Treatment-Resistant Depression in Traumatic Brain Injury: a randomized, controlled, double blinded pilot study.

Author information

1
McLean Hospital, Neurology, Belmont, Massachusetts, United States.
2
Washington University in Saint Louis School of Medicine, 12275, Psychiatry, Saint Louis, Missouri, United States.
3
Center For Neuroscience and Regenerative Medicine, Bethesda, Maryland, United States ; shan.siddiqi@mgh.harvard.edu.
4
University of Iowa Roy J and Lucille A Carver College of Medicine, 12243, Psychiatry, Iowa City, Iowa, United States ; nicholas-trapp@uiowa.edu.
5
Washington University in Saint Louis School of Medicine, 12275, Neurosurgery, Saint Louis, Missouri, United States ; hackerc@wustl.edu.
6
Washington University in Saint Louis School of Medicine, 12275, Psychiatry, Saint Louis, Missouri, United States ; laumannt@wustl.edu.
7
Washington University in Saint Louis School of Medicine, 12275, Psychiatry, Saint Louis, Missouri, United States ; kandalas@wustl.edu.
8
Washington University in Saint Louis School of Medicine, 12275, Neurology, Saint Louis, Missouri, United States ; hongxin25@gmail.com.
9
Washington University in Saint Louis School of Medicine, 12275, Psychiatry, Saint Louis, Missouri, United States ; trillol@wustl.edu.
10
Center For Neuroscience and Regenerative Medicine, Bethesda, Maryland, United States ; pashtun-poh.shahim@nih.gov.
11
Washington University School of Medicine, Neurosurgery, St. Louis, Missouri, United States ; leuthardte@wustl.edu.
12
Washington University in Saint Louis School of Medicine, 12275, Neurology, Saint Louis, Missouri, United States ; alexandre.carter@wustl.edu.
13
Uniformed Services University of the Health Sciences, 1685, Neurology, Bethesda, Maryland, United States.
14
Center For Neuroscience and Regenerative Medicine, Bethesda, Maryland, United States.
15
Washington University in Saint Louis School of Medicine, 12275, Neurology, Saint Louis, Missouri, United States ; david.brody@nih.gov.

Abstract

BACKGROUND:

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy, but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with TBI.

METHODS:

14 Subjects with treatment-resistant depression and prior concussive or moderate TBI received resting-state fMRI scans with individual-level RSNM. Subjects were randomized to 20 sessions of bilateral rTMS (4000 left-sided excitatory pulses, 1000 right-sided inhibitory pulses) or sham. Treatment was targeted to the dorsolateral prefrontal cluster with maximal difference between DAN and DMN correlations. The primary outcome was Montgomery-Asberg Depression Rating Scale (MADRS).

RESULTS:

Mean MADRS improvement was 56% ± 14% (n=9) with active treatment and 27% ± 25% (n=5) with sham (Cohen's d=1.43). One subject randomized to sham withdrew prior to starting treatment. There were no seizures or other significant adverse events. MADRS improvement was inversely correlated with functional connectivity between the right-sided stimulation site and the subgenual anterior cingulate cortex (sgACC) (r=-0.68, 95% CI 0.03 - 0.925). Active treatment led to increased sgACC-DMN connectivity (Cohen's d=1.55) and increased sgACC anti-correlation with the left- and right-sided stimulation sites (Cohen's d= -1.22 and -0.69, respectively).

CONCLUSIONS:

This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.

KEYWORDS:

CLINICAL TRIAL; MRI; PROSPECTIVE STUDY; THERAPEUTIC APPROACHES FOR THE TREATMENT OF CNS INJURY; TRAUMATIC BRAIN INJURY

PMID:
30381997
DOI:
10.1089/neu.2018.5889

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