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

Abstract

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.

Characterization of the hemodynamic response in the rat lumbar spinal cord using intrinsic optical imaging and laser speckle

“…Interestingly, the functional response appeared 2-3 s later than that using alpha-chloralose. The amplitude of the response was also slightly decreased, as already observed in human (Abel et al, 2003).…”

Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis

“…First, we cannot fully exclude the possibility that our imaging findings were associated with an unspecific effect of S-ketamine on cerebral blood flow. However, recent studies suggest that ketamine administration rather results in an altered BOLD response specific to the cognitive task (Northoff et al 2005) or the emotional stimuli (Abel et al 2003) presented than in a nonspecific global effect on cerebral blood flow per se. Further support for this argument comes from animal studies, which also suggest that ketamine has no effects on vascular mechanisms beyond its specific effects on neural activation (Burdett et al 1995).…”

Does neuroimaging research examining the pathophysiology of posttraumatic stress disorder require medication-free patients?

“…The consequences of ketamine and placebo and their effects on BOLD versus alterations in cognitive state in healthy participants has also been examined. 43 The changes in BOLD signal during perception of the face-nonface contrast exhibited widespread BOLD changes. However, in the placebo group compared with in the ketamine group, there was significantly greater BOLD signal change only in the middle occipital gyrus (BA 18) and the precentral gyrus (BA 4).…”

“…The authors suggested that the BOLD signal changes represented task-dependent effects of drug or placebo, rather than taskindependent effects of drug. 43 The effects of lamotrigine on BOLD signal changes induced by transcranial magnetic stimulation (TMS) have also been examined in healthy participants. 44 Lamotrigine at clinically relevant serum concentrations diffusely inhibited cortical activation induced by TMS applied over the motor cortex.…”