Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin.
OBJECTIVE
The acute effects of a single, low dose of phenytoin on behavioral and neurophysiological measures of cognitive function were examined in healthy adults.


METHODS
Electroencephalograms (EEGs) were recorded from 7 healthy volunteers while they performed spatial working memory tasks and while they rested quietly. Behavioral measures, EEG power spectra, and event-related potentials (ERPs) were compared between separate sessions in which subjects ingested either 10mg/kg of phenytoin or placebo.


RESULTS
Peak serum levels of phenytoin were in the low therapeutic range. Although participants reported subjective effects of the drug, task accuracy and response time were not affected. In the resting EEG, phenytoin decreased power in the alpha band. In the task-related EEG, the frontal midline theta signal was enhanced in response to increased task difficulty following placebo but not following phenytoin. An attention-related augmentation of the N160 ERP to matching stimuli was also reduced by phenytoin.


CONCLUSIONS
Neurophysiological measures displayed sensitivity to subtle alterations in attentional processing even in response to a dose of phenytoin too low to produce behavioral impairment. Such results indicate that EEG and ERP measures can provide information about the neurocognitive side effects of medications that cannot be inferred from cognitive task performance measures alone.
Chung
Steve S
SS
San Francisco Brain Research Institute and SAM Technology, 425 Bush Street Fifth Floor, San Francisco, CA 94108, USA.
McEvoy
Linda K
LK
Smith
Michael E
ME
Gevins
Alan
A
Meador
Kimford
K
Laxer
Kenneth D
KD
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood; D003071:Cognition / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects*; D018913:Event-Related Potentials, P300 / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D010672:Phenytoin / Q000009:adverse effects* / Q000097:blood; D011597:Psychomotor Performance / Q000187:drug effects*; D012146:Rest
D000927:Anticonvulsants; D010672:Phenytoin