Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study.
BACKGROUND
Glutamatergic dysfunction at N-methyl-D: -aspartate (NMDA) receptors has been proposed as a neurochemical model for schizophrenia. A key feature of this disorder is impairments in cognitive function.


OBJECTIVE
The present study sought to investigate the effects of ketamine, an NMDA antagonist, on the performance and neural correlates of verbal fluency, a task that engages executive function.


METHODS
Ten healthy dextral male volunteers received intravenous placebo normal saline or ketamine (bolus of 0.23 mg/kg and infusion of 0.65 mg/kg), administered in a double-blind, randomized order, during two functional magnetic resonance imaging sessions. During scanning, subjects performed a verbal fluency task. Two levels of cognitive load were examined in the task, and overt responses were acquired in order to measure subject performance on-line.


RESULTS
Ketamine induced symptoms in the healthy individuals comparable to an acute psychotic state. Although ketamine did not significantly impair task performance relative to placebo, an interaction of task demand with ketamine was observed in the anterior cingulate, prefrontal, and striatal regions.


CONCLUSIONS
The behavioural and functional effects of ketamine during verbal fluency in healthy individuals were comparable to those evident in patients with schizophrenia. The findings support a role for glutamatergic dysfunction in the pathophysiology of schizophrenia.
Fu
Cynthia H Y
CH
Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. c.fu@iop.kcl.ac.uk
Abel
Kathryn M
KM
Allin
Matthew P G
MP
Gasston
David
D
Costafreda
Sergi G
SG
Suckling
John
J
Williams
Steve C R
SC
McGuire
Philip K
PK
D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists; D006801:Humans; D007649:Ketamine; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011605:Psychoses, Substance-Induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013647:Task Performance and Analysis; D014705:Verbal Behavior / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine