Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change in blood flow versus change in cognitive state.

No human fMRI studies have examined ketamine effects on the BOLD signal change associated with cognitive task performance. We wished to distinguish between effects on 1) cerebral blood flow, with resultant change in BOLD signal; and 2) cognition and neural mechanisms underlying BOLD signal change associated with task performance. Eight right-handed men (mean age 28.75 years) received ketamine or saline i.v. in a randomized, double-blind manner (bolus 0.23 mg/kg; 0.5 mg/kg over 45 min to a maximum 1 hr). Subjects viewed 10 alternating 30-sec blocks of faces with neutral expressions and a fixation cross and discriminated gender of faces. Gradient echo echoplanar images were acquired on a GE Signa 1.5 T Neurovascular system. One hundred T2-weighted images depicting BOLD contrast were acquired over 5 min (for each task) at each of 14 near-axial noncontiguous 7-mm thick planes. Ketamine significantly increased dissociative phenomena and negative symptoms, but did not affect performance of the gender discrimination task. Significant BOLD signal change was demonstrated predominantly in occipitotemporal cortex with both ketamine and placebo. Only two clusters in middle occipital gyrus (BA 18) and precentral gyrus (BA 4) showed significantly decreased BOLD signal change during ketamine compared to placebo. BOLD signal change was not significantly greater in any region during ketamine. Our findings demonstrate subtle rather than major differences between the effects of ketamine and placebo upon the BOLD signal change during perception of face-non face contrast. We suggest that they represent task-dependent effects of the drug/placebo, rather than task-independent effects of the drug per se, and indicate that the effects of ketamine on cerebral blood flow are predominantly focal and task-dependent, rather than global and task-independent.