Figure 3. Paradoxical Excitation, Cerebral Metabolism, and Electroencephalographic (EEG) Activity in Stages of Coma Recovery.

Cortical damage causes loss of excitatory inputs from the frontal cortex to the median spiny neurons in the striatum, as shown in Panel A. Normal striatal inhibition of the globus pallidus interna is lost, and the globus pallidus interna tonically inhibits the thalamus. Zolpidem and propofol may bind to GABA_A1 receptors in the globus pallidus interna, blocking its inhibitory inputs to the thalamus; as a result, excitatory cortical inputs from the thalamus are restored, causing paradoxical excitation.⁷³ Panel B schematically depicts changes in cerebral metabolism as measured by positron emission tomographic (PET) scanning and on electroencephalography (EEG) at different stages of coma recovery. In the awake state, the EEG pattern is active and cerebral metabolism is globally active. Paradoxical excitation induced by the administration of zolpidem, which is associated with behavioral improvement in some minimally conscious patients, is reflected by an active EEG pattern with reduced prefrontal cortex metabolism. Patients in minimally conscious and vegetative states may show EEG anteriorization, with alpha, theta, and delta EEG patterns and decreased metabolism in the frontal cortex, striatum, and thalamus. Burst suppression in coma correlates with globally depressed metabolism. General anesthesia results in similar EEG patterns. A denotes anterior, and P posterior.