TY - JOUR
T1 - A pilot trial examining the merits of combining amantadine and repetitive transcranial magnetic stimulation as an intervention for persons with disordered consciousness after TBI
AU - Bender Pape, Theresa L.
AU - Herrold, Amy A.
AU - Livengood, Sherri L.
AU - Guernon, Ann
AU - Weaver, Jennifer A.
AU - Higgins, James P.
AU - Rosenow, Joshua M.
AU - Walsh, Elyse
AU - Bhaumik, Runa
AU - Pacheco, Marilyn
AU - Patil, Vijaya K.
AU - Kletzel, Sandra
AU - Conneely, Mark
AU - Bhaumik, Dulal K.
AU - Mallinson, Trudy
AU - Parrish, Todd
N1 - Funding Information:
Dr Bender Pape reports grants from the National Institute of Child Health and Human Development of the National Institutes of Health (NICHD, NIH), Defense Health Agency, RDA Directorate, US Army Medical Research Acquisition Activity, nonfinancial support from National Center for Research Resources (NCRR) of the NIH, nonfinancial support from US Department of Veterans Affairs (VA), Office of Research and Development (ORD), Million Veterans’ Program, Edward Hines Jr VAH grants from Nick Kot Charity for TBI, nonfinancial support from Wings-of-Hope, grants from Disabled Veterans National Foundation, grants from Christus Health, grants from Houston area Phi Mu Alumnae Association, during the conduct of the study; personal fees from Hellius Medical, outside the submitted work; Dr Bender Pape has a patent pending. Dr Bender Pape also reports employment with Edward Hines Jr VA Hospital and Northwestern University Feinberg School of Medicine, Department of Physical Medicine and Rehabilitation. In addition, Dr Bender Pape received travel reimbursements from the Chicago Association for Research and Education in Science (CARES).
Funding Information:
Dr Herrold reports grants from the US Department of Veterans Affairs, ORD, Rehabilitation Research and Development Service as well as personal fees from University of Minnesota Duluth, Loyola University of Chicago, and the University of Illinois at Chicago as well as travel reimbursements from University of Minnesota Duluth and the CARES, all of which is outside of submitted work. Dr Herrold also reports employment with Edward Hines Jr VA
Funding Information:
Drs Livengood, Guernon, Mallinson, and Walsh report salary support from grants awarded to Dr Bender Pape. In addition, Dr Guernon reports employment with Northwestern Medicine’s Marianjoy Rehabilitation Hospital. Dr Walsh also reports employment with CARES and the Shirley Ryan Ability Lab. Dr Livengood also reports VA grants through Office of Academic Affiliations and employment with CARES as well as a pending patent.
Funding Information:
Ms Weaver reports salary support from grants awarded to Drs Bender Pape and Mallinson. Ms Weaver and Dr Mallinson each report employment with The George Washington University, Department of Clinical Research and Leadership, School of Medicine and Health Sciences. Dr Mallinson also reports grants from the American Institutes for Research.
Funding Information:
Dr Parrish and Mr Higgins report employment with Northwestern University Feinberg School of Medicine, Department of Radiology. In addition, Dr Parrish reports grants from the NIH.
Funding Information:
Dr Rosenow reports grants from SPR Corporation, Boston Scientific, Voyager Therapeutics, and Deep Brain Innovations. In addition, he reports employment with the Northwestern Medical Community and personal fees from Boston Scientific, outside the submitted work.
Funding Information:
Drs Dulal Bhaumik and Runa Bhaumik report employment with the University of Illinois at Chicago, Department of Psychiatry, Biostatistical Research Center, Division of Epidemiology and Biostatistics. Dr Dulal Bhaumik also reports grants from the NIH.
Funding Information:
The work reported here was supported by NIH 1R21HD075192-01A1 to Dr Bender Pape.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Amantadine
KW - Clinical trial
KW - Default mode network
KW - Disorders of consciousness
KW - Functional MRI
KW - Intervention
KW - Neurobehavioral
KW - Transcranial magnetic stimulation
KW - Traumatic brain injury
KW - Vegetative state
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U2 - 10.1097/HTR.0000000000000634
DO - 10.1097/HTR.0000000000000634
M3 - Article
C2 - 33165151
AN - SCOPUS:85095977226
VL - 35
SP - 371
EP - 387
JO - Journal of Head Trauma Rehabilitation
JF - Journal of Head Trauma Rehabilitation
SN - 0885-9701
IS - 6
ER -