Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury
Shawniqua T Williams,
Mary M Conte,
Andrew M Goldfine,
Quentin Noirhomme,
Olivia Gosseries,
Marie Thonnard,
Bradley Beattie,
Jennifer Hersh,
Douglas I Katz,
Jonathan D Victor,
Steven Laureys,
Nicholas D Schiff
Affiliations
Shawniqua T Williams
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, United States
Mary M Conte
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, United States; Brain Mind Research Institute, Weill Cornell Medical College, New York, United States
Andrew M Goldfine
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, United States
Quentin Noirhomme
Coma Science Group, Cyclotron Research Centre, University of Liège and University Hospital of Liège, Liège, Belgium; Neurology Department, University of Liège and University Hospital of Liège, Liège, Belgium
Olivia Gosseries
Coma Science Group, Cyclotron Research Centre, University of Liège and University Hospital of Liège, Liège, Belgium; Neurology Department, University of Liège and University Hospital of Liège, Liège, Belgium
Marie Thonnard
Coma Science Group, Cyclotron Research Centre, University of Liège and University Hospital of Liège, Liège, Belgium; Neurology Department, University of Liège and University Hospital of Liège, Liège, Belgium
Bradley Beattie
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, United States
Jennifer Hersh
Division of Medical Ethics, Weill Cornell Medical College, New York, United States
Douglas I Katz
Brain Injury Program, Braintree Rehabilitation Hospital, Boston University School of Medicine, Braintree, United States
Jonathan D Victor
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, United States; Brain Mind Research Institute, Weill Cornell Medical College, New York, United States
Steven Laureys
Coma Science Group, Cyclotron Research Centre, University of Liège and University Hospital of Liège, Liège, Belgium; Neurology Department, University of Liège and University Hospital of Liège, Liège, Belgium
Nicholas D Schiff
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, United States; Brain Mind Research Institute, Weill Cornell Medical College, New York, United States
Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors.
