Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse

Abstract

Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

Figure 1. Parietal cortex CMRglc increased between sessions in the MA abuse group, more than in the control group

The figures are depicted in neurological orientation. The gray-scale image is a T1 structural MRI that is representative of MNI space, where positive values of the x, y, and z coordinates approximately represent mm to the right, anterior and superior relative to the sagittal midpoint of the anterior commissure. The a priori parietal lobe regions of interest (ROIs) are outlined in light blue. Red/yellow colors indicate greater increases in CMRglc from initial PET session to four weeks later in 9 MA, as compared to 7 control subjects (p < .01 uncorrected).

Figure 2. Between-session directional change in relative radioactivity of medial orbitofrontal cortex was inversely correlated with vigilance reaction time (RT) in the MA abuse group

Red/yellow colors indicate areas where the amount of RT slowing from initial PET session to four weeks later was associated with decreased regional relative radioactivity in 10 MA subjects (p < .01 uncorrected).

Figure 3. Between-session directional change in relative radioactivity of ventral striatum was directly correlated with self-reported depressive symptoms in the MA abuse group

Red/yellow colors indicate areas where change in BDI score from initial PET session to four weeks later was associated with change in regional relative radioactivity in 10 MA subjects (p < .01 uncorrected).