Functional MRI detection of pharmacologically induced memory impairment

Abstract

To examine alterations in brain activation associated with pharmacologically induced memory impairment, we used functional MRI (fMRI) to study the effects of lorazepam and scopolamine on a face-name associative encoding paradigm. Ten healthy young subjects were scanned on four occasions, 2 weeks apart; they were administered i.v. saline during two placebo-scanning sessions and then alternately administered i.v. lorazepam (1 mg) or scopolamine (0.4 mg) in a double-blind, randomized, cross-over design. Both the extent and magnitude of activation within anatomic regions of interest (ROIs) were examined to determine the reproducibility of activation in the placebo sessions and the regional specificity of the pharmacologic effects. Activation within all ROIs was consistent across the two placebo scans during the encoding of novel face-name pairs (compared with visual fixation). With the administration of either lorazepam or scopolamine, significant decreases were observed in both the extent and magnitude of activation within the hippocampal, fusiform, and inferior prefrontal ROIs, but no significant alterations in activation in the striate cortex were found. Both medications impaired performance on postscan memory measures, and significant correlations between memory performance and extent of activation were found in hippocampal and fusiform ROIs. These findings suggest that pharmacologic effects can be detected with fMRI by using a reproducible experimental paradigm and that medications that impair memory also diminish activation in specific brain regions thought to subserve complex memory processes.

Figures

Figure 1

Group fMRI data (n = 10) for the Novel face–name pairs vs. Fixation contrast is shown superimposed on a three-dimensional reconstruction of an individual subject's structural data in lateral view of left hemisphere. Activation shown in orange to yellow represents voxels with greater activity in the Novel compared with Fixation conditions. Activation shown in blue represents voxels with greater activity in Fixation condition compared with Novel. All four sessions show a similar pattern of activation in the occipital cortex.

Figure 2

Group fMRI data for the Novel vs. Fixation contrast is shown in the ventral view of the right hemisphere. All four sessions show a similar pattern of activation in striate and lateral extrastriate cortices, but there is reduced activation in the medial inferior temporal cortex, confined within the fusiform gyrus, that was observed with the administration of both lorazepam and scopolamine.

Figure 3

Group fMRI data for the Novel vs. Fixation contrast shown on a coronal image at the level of the anterior hippocampus, showing reduced activation in the lorazepam and scopolamine sessions.

Figure 4

Magnetic resonance signal averaged time courses taken from voxels that activated during both placebo scans (P 1 and P 2), within the striate cortex (Left) and hippocampus (Right), across the four imaging sessions. The signal in striate remains paradigm-linked across all four sessions, whereas the signal in the hippocampus shows an altered pattern in the lorazepam (LOR) and scopolamine (SCO) sessions.