Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury

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.