182.4/LL36

Partial restoration of behavioral responsiveness and arousal regulation by electrical stimulation of the human intralaminar thalamic nuclei

Georgia World Congress Center: Halls B3-B5

Sunday, Oct 15, 2006, 11:00 AM -12:00 PM

*N. D. SCHIFF¹, J. GIACINO², K. KALMAR², E. KOBYLARZ¹, K. BAKER³, S. FARRIS³, A. MACHADO³, J. VICTOR¹, C. MCCAGG², F. PLUM¹, J. FINS⁴, A. REZAI³;
¹Dept Neurol & Neurosci, Weill Cornell Med Col, NY, NY, ²Neurosci, JFK Johnson Reh, Edison, NY, ³Cen Neurol Restor, Cleveland Clinic Found, Cleveland, OH, ⁴Div Med Ethics, Weill Cornell Med Col, NY, NY.

As part of a pilot clinical trial, central thalamic deep brain stimulation (DBS) electrodes were implanted bilaterally in a 38 yr-old male who remained in a minimally conscious state for 6 years following a severe traumatic brain injury. Although the patient was unable to communicate reliably, prior characterization of brain function using fMRI showed preservation of bi-hemispheric large-scale cerebral language networks. PET and quantitative EEG revealed that cerebral metabolism and thalamocortical dynamics during wakefulness were markedly abnormal. DBS electrodes targeted the anterior intralaminar thalamic nuclei and adjacent paralaminar regions of thalamic association nuclei. During a 4 month pre-operative evaluation in a comprehensive inpatient rehabilitation setting, communication responses remained limited to inconsistent thumb movements for activation of a toggle switch. Communication remained unreliable across the first 6 weeks post-surgery with DBS off. A 5 month pre-treatment assessment of stimulation parameters followed to determine optimal settings for use in a 6 month double-blinded alternating on/off trial period. Trial results show a consistent trend of improved verbal and behavioral responsiveness during the ON condition with statistically significant improvements in attentive behavior, functional use of the left upper extremity and oral feeding. Comparison of the presurgical and pre-titration baselines compared to trial-DBS OFF measurements shows a marked increase in verbal output and communication ability during the OFF condition suggesting DBS carry-over effects. We interpret these results as evidence of partial functional restoration of frontal cortical systems involved in arousal regulation and behavioral drive. Direct activation of neocortical and basal ganglia neurons and suppression of abnormal background brain dynamics may play a role in the observed effects. Carry-over effects likely reflect the direct influence of central thalamic stimulation on neocortical learning and memory systems. This is the first controlled DBS study of functional restoration in the setting of long-standing brain injury.

  N.D. Schiff, is a paid consultant and advisor to IntElect Medical, Inc that supports the clinical trial and an inventor through Cornell Univ. of technology involved in this study, Other; J. Giacino, None; K. Kalmar, None; E. Kobylarz, None; K. Baker, None; S. Farris, None; A. Machado, None; J. Victor, None; C. McCagg, None; F. Plum, None; J. Fins, None; A. Rezai, Dr. Rezai is a paid consultant and advisor to IntElect Medical, Inc that supports the clinical trial., Other.

NS43451

Dana Foundation

IntElect Medical, Inc

Cleveland Clinic Innovations