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

Nicholas D Schiff; Joseph T Giacino; Christopher R Butson; Eun Young Choi; Jonathan L Baker; Kyle P O'Sullivan; Andrew P Janson; Michael Bergin; Helen M Bronte-Stewart; Jason Chua; Laurel DeGeorge; Sureyya Dikmen; Adam Fogarty; Linda M Gerber; Mark Krel; Jose Maldonado; Matthew Radovan; Sudhin A Shah; Jason Su; Nancy Temkin; Thomas Tourdias; Jonathan D Victor; Abigail Waters; Stephanie A Kolakowsky-Hayner; Joseph J Fins; Andre G Machado; Brian K Rutt; Jaimie M Henderson

doi:10.1038/s41591-023-02638-4

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

Nat Med. 2023 Dec;29(12):3162-3174. doi: 10.1038/s41591-023-02638-4. Epub 2023 Dec 4.

Authors

Nicholas D Schiff^{1

2}, Joseph T Giacino^{3

4}, Christopher R Butson^{5

6}, Eun Young Choi⁷, Jonathan L Baker⁸, Kyle P O'Sullivan⁵, Andrew P Janson^{5

9}, Michael Bergin³, Helen M Bronte-Stewart⁷, Jason Chua¹⁰, Laurel DeGeorge⁸, Sureyya Dikmen¹¹, Adam Fogarty⁷, Linda M Gerber^{10

12}, Mark Krel⁷, Jose Maldonado¹³, Matthew Radovan¹⁴, Sudhin A Shah¹⁵, Jason Su¹⁶, Nancy Temkin¹⁷, Thomas Tourdias¹⁸, Jonathan D Victor^{8

19}, Abigail Waters³, Stephanie A Kolakowsky-Hayner⁷, Joseph J Fins¹², Andre G Machado²⁰, Brian K Rutt^{21

22

23}, Jaimie M Henderson^{24

25

26}

Affiliations

¹ Feil Family Brain Mind Institute, Weill Cornell Medicine, New York, NY, USA. [email protected].
² Department of Neurology, Weill Cornell Medicine, New York, NY, USA. [email protected].
³ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, USA.
⁴ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
⁵ Scientific Computing and Imaging Institute Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
⁶ Norman Fixel Institute for Neurological Diseases Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, USA.
⁷ Department of Neurosurgery, Stanford University, Stanford, CA, USA.
⁸ Feil Family Brain Mind Institute, Weill Cornell Medicine, New York, NY, USA.
⁹ Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
¹⁰ Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
¹¹ Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA.
¹² Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
¹³ Department of Psychiatry, Stanford University, Stanford, CA, USA.
¹⁴ Department of Computer Science, Stanford University, Stanford, CA, USA.
¹⁵ Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
¹⁶ Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
¹⁷ Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
¹⁸ Department of Neuroimaging, University of Bordeaux, Nouvelle-Aquitaine, France.
¹⁹ Department of Neurology, Weill Cornell Medicine, New York, NY, USA.
²⁰ Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
²¹ Department of Radiology, Stanford University, Stanford, CA, USA.
²² Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
²³ Bio-X Program, Stanford University, Stanford, CA, USA.
²⁴ Department of Neurosurgery, Stanford University, Stanford, CA, USA. [email protected].
²⁵ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. [email protected].
²⁶ Bio-X Program, Stanford University, Stanford, CA, USA. [email protected].

Abstract

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 .

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial

MeSH terms

Brain Injuries, Traumatic* / therapy
Deep Brain Stimulation* / methods
Feasibility Studies
Humans
Quality of Life
Thalamus / physiology

Associated data

ClinicalTrials.gov/NCT02881151

Abstract

Publication types

MeSH terms

Associated data

Grants and funding