‘K’ is for ketamine: An FMRI study of the neural correlates of a ketamine-induced psychotic state on word generation (original) (raw)

2003, Schizophrenia Research

Introduction: Phencyclidine (PCP) produces a brief psychotic state in healthy volunteers that is comparable with the symptoms of schizophrenia. A fundamental neurocognitive deficit in schizophrenia is impairments in language processing. Letter verbal fluency is a classical measure of general language abilities in which subjects are required to generate a word in response to letter cues. We sought to examine the neural correlates of an acute psychotic state induced by ketamine (an analogue of PCP) in healthy volunteers as they performed a verbal fluency task. Methods: Eleven healthy male volunteers (mean age 28 years) received either intravenous ketamine or placebo in a double-blind manner, while performing an overt verbal fluency task. FMRI data were acquired at 1.5 T. Results: During the ketamine infusion, subjects developed acute psychotic symptoms. The fMRI data reve',ded a main effect of ketamine, as compared to placebo, with increased activity in the anterior cingulate, prefrontal and parietal cortices, insula and basal ganglia. During the verbal fluency task, relative to placebo, ketamine was associated with greater activation in the prefrontal cortices and basal ganglia. Discussion: A ketamine-induced psychotic state was associated with increased activity in a distributed set of cortical and subcortical regions and a significant modulation of task-related activation during verbal fluency. The latter interaction implicates a prefrontal-striatal network that normally mediates executive aspects of language function in the pathophysiology of an acute psychotic state.