A pilot trial examining the merits of combining amantadine and repetitive transcranial magnetic stimulation as an intervention for persons with disordered consciousness after TBI

Document Type

Journal Article

Publication Date

11-1-2020

Journal

Journal of Head Trauma Rehabilitation

Volume

35

Issue

6

DOI

10.1097/HTR.0000000000000634

Keywords

Amantadine; Clinical trial; Default mode network; Disorders of consciousness; Functional MRI; Intervention; Neurobehavioral; Transcranial magnetic stimulation; Traumatic brain injury; Vegetative state

Abstract

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. Objective: Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. Participants: Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). Design: Alternate treatment-order, within-subject, baseline-controlled trial. Main Measures: For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. Results: Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. Conclusions: For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

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