Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nuc...

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Published inNature medicine Vol. 29; no. 12; pp. 3162 - 3174
Main Authors Schiff, Nicholas D., Giacino, Joseph T., Butson, Christopher R., Choi, Eun Young, Baker, Jonathan L., O’Sullivan, Kyle P., Janson, Andrew P., Bergin, Michael, Bronte-Stewart, Helen M., Chua, Jason, DeGeorge, Laurel, Dikmen, Sureyya, Fogarty, Adam, Gerber, Linda M., Krel, Mark, Maldonado, Jose, Radovan, Matthew, Shah, Sudhin A., Su, Jason, Temkin, Nancy, Tourdias, Thomas, Victor, Jonathan D., Waters, Abigail, Kolakowsky-Hayner, Stephanie A., Fins, Joseph J., Machado, Andre G., Rutt, Brian K., Henderson, Jaimie M.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.12.2023
Nature Publishing Group
Subjects
631/378/2649/1310
692/617/375/1345
Biomedical and Life Sciences
Biomedicine
Brain
Brain Injuries, Traumatic - therapy
Cancer Research
Deep brain stimulation
Deep Brain Stimulation - methods
Effectiveness
Executive function
Feasibility Studies
Head injuries
Humans
Infectious Diseases
Information processing
Injury prevention
Metabolic Diseases
Molecular Medicine
Neuroimaging
Neurosciences
Processing speed
Quality of Life
Speed limits
Stimulation
Thalamus
Thalamus - physiology
Traumatic brain injury
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ISSN1078-8956
1546-170X
1546-170X
DOI10.1038/s41591-023-02638-4

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Summary:Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract. Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test. All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases. CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery. ClinicalTrials.gov identifier: NCT02881151 . A phase 1 feasibility trial shows that bilateral deep brain stimulation within the central lateral thalamus can be safely applied and is associated with improved executive control.
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NS, JH, JG, CB, AM designed the study.
EC, JB, SS developed the overall study design for neurophysiological data acquisition.
JG, NS, LG developed study design for outcome assessment.
JG, AW, LG, JC analyzed behavioral data.
EC, JB, MK analyzed cortical evoked potential data.
JJF developed ethical framework and guidance; PI of companion BRAIN Initiative study (1RF1MH12378–01) tracking participant and family perspectives which informed subject selection and enrollment.
All authors provided substantive feedback for revision of manuscript.
CB, AJ, KO designed and performed analysis of bioelectrical field modeling.
EC, TT, JS, MR, BR, AJ, KO, CB designed and performed analysis of neuroimaging data.
NS and JV designed and performed analysis of supplementary Dikmen et al. (2003) dataset. TT, JS, MR, BR developed the CL segmentation method.
EC, BR acquired neuroimaging data.
EC, JB, designed cortical evoked potential experiments.
NS, JH, JG, CB, BR drafted the manuscript.
HBS provided neurophysiology acquisition and interpretation during surgical implants.
JM acted as an independent consultation-liaison psychiatrist responsible for determination of decision-making capacity for each subject prior to study enrollment.
LD, coordinated the study components, FDA regulatory compliance, and patient recruitment liaison with PatientWing.
JH acted as physician sponsor of the FDA Investigational Device Exemption (IDE) and performed all surgical implants.
Author Contributions
SD, NT contributed supplementary data from University of Washington study and support in the use, analysis, and interpretation of these data (Dikmen et al. 2003).
NS acted as administrative PI of UH3 grant.
ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/s41591-023-02638-4