Pseudocontinuous Arterial Spin Labeling Reveals Dissociable Effects of Morphine and Alcohol on Regional Cerebral Blood Flow

Abstract

We have examined sensitivity and specificity of pseudocontinuous arterial spin labeling (PCASL) to detect global and regional changes in cerebral blood flow (CBF) in response to two different psychoactive drugs. We tested alcohol and morphine in a placebo-controlled, double-blind randomized study in 12 healthy young men. Drugs were administered intravenously. Validated pharmacokinetic protocols achieved minimal intersubject and intrasubject variance in plasma drug concentration. Permutation-based statistical testing of a mixed effect repeated measures model revealed a widespread increase in absolute CBF because of both morphine and alcohol. Conjunction analysis revealed overlapping effects of morphine and alcohol on absolute CBF in the left anterior cingulate, right hippocampus, right insula, and left primary sensorimotor areas. Effects of morphine and alcohol on relative CBF (obtained from z-normalization of absolute CBF maps) were significantly different in the left putamen, left frontoparietal network, cerebellum, and the brainstem. Corroborating previous PET results, our findings suggest that PCASL is a promising tool for central nervous system drug research.

The impact of “physiological correction” on functional connectivity analysis of pharmacological resting state fMRI

“…However, a regional change in cerebral blood flow to the cerebellum is not necessarily a non-specific hemodynamic response. As we have shown before (Khalili-Mahani et al, 2011), the impact of morphine and alcohol on the cerebellar perfusion is independent of global changes in cerebral blood flow. Therefore, the observed effect might indicate an adaptive response to morphine effects on breathing function.…”

Alcohol-Induced Impairment of Inhibitory Control Is Linked to Attenuated Brain Responses in Right Fronto-Temporal Cortex

“…Alcohol effects on inhibition-related brain responses in the RIFG/insula (Figure 4D; Pearson's r (40)=-.35, p =.024), and the occipito-temporal cortex (Figure 4E; Pearson's r (40)=-.33, p =.032) correlated negatively with alcohol-induced impaired inhibitory control. The negative correlation indicates larger activation decreases with worsened inhibitory control under alcohol.…”

“…We tested the hypothesis that alcohol decreases brain responses in the right frontal portion of the inhibition-related fronto-subcortical network that has been shown to be sensitive to impaired inhibitory control (21; 29-31), and thereby leads to alcohol-induced impairment of inhibitory control. Additionally, we measured cerebral perfusion using arterial spin labeling (ASL) MRI (39) to test whether alcohol effects on task-related blood oxygenation level-dependent (BOLD) responses were confounded by vasoactive alcohol effects on perfusion (40-42). Furthermore, we tested in the same sample whether alcohol-induced impairment of inhibitory control predicted alcohol consumption levels in a separate free-access ASA experiment (cf, 43).…”

Imaging Drugs with and without Clinical Analgesic Efficacy

“…It is noted that phMRI infusion analysis procedures did vary slightly between the previous and the current study, and may contribute to the differences observed between the two sets of results. Moreover, in a recent study by Khalili-Mahani et al (2011), increases in cerebral blood flow were observed in the limbic and sensory regions following administration of morphine. This previous finding is also in line with the current phMRI results of BUP.…”