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Aaron Warren, PhD

Job Title

Post-doctoral Research Fellow

Academic Rank

Fellow or Postdoc




Aaron E.L Warren, Marina Raguž, Darko Chudy, John D. Rolston

Principal Investigator

John D. Rolston



Optimal targets, connectivity, and tissue integrity for deep brain stimulation in patients with disorders of consciousness

Scientific Abstract

Introduction: Deep brain stimulation (DBS) is a potential treatment to restore arousal and awareness in patients who develop disorders of consciousness (DOC) following traumatic brain injuries. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential.

Objective: To determine whether DBS outcomes in DOC are associated with stimulation locations, connectivity of stimulation sites, and tissue integrity.

Methods: Retrospective analysis of 40 adults with DOC undergoing unilateral DBS targeting the thalamic centromedian nucleus. Patients were deemed ‘responders’ or ‘non-responders’ using standardized coma scales. Associations were explored with age, T1-weighted MRI brain volumes, and diffusion MRI connectivity calculated from DBS sites.

Results: 10/40 patients were responders. Favorable response was associated with younger age and greater preservation of whole-brain grey matter and putamen, pallidum, caudate, and cerebellum. In responders, stimulation fields engaged the parafascicular and reticular nuclei, and connectivity was higher with frontal cortex, putamen, pallidum, caudate, and cerebellum.

Conclusions: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, pallidum, caudate, and cerebellum, stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, targeting, and post-implantation programming.

Lay Abstract

Disorders of consciousness (DOC) are neurological conditions involving reduced or absent awareness/arousal (for example, coma or minimally conscious states). They can result from damage to the brain, like traumatic brain injuries, stroke, or after cardiac arrest. There are few treatments available. One emerging treatment is deep brain stimulation (DBS), where electrodes are surgically implanted into key brain structures and deliver electrical stimulation.

We aimed to explore whether the efficacy of DBS for DOC is associated with the type of patient, where stimulation occurs in the brain, the connectivity of stimulated locations, and the appearance of the brain on structural MRI scans. We studied 40 patients who had DOC of various severities and measured their response to DBS using standardized coma scales.

10/40 patients were ‘responders’. Compared to non-responders, the responders tended to be younger at the time of their brain injury and their MRI scans showed more preservation of grey matter. They also had stimulation of different regions in a part of the brain called the thalamus, and they had more connections between their stimulation site and other regions including the frontal lobe.

The findings will help with selecting patients who are good candidates for DBS and optimizing DBS surgery.

Clinical Implications

The findings will help select patients who are optimal candidates for DBS, will guide future DBS surgeries to target the therapeutically optimal locations we have identified, and will assist with optimizing stimulation programming in patients with DBS devices already implanted.