Conditional discrimination and reversal in amnesia subsequent to hypoxic brain injury or anterior communicating artery aneurysm rupture

Abstract

Human anterograde amnesia can develop following bilateral damage to the hippocampus and medial temporal lobes, as in hypoxic brain injury, or following damage to the basal forebrain, as following anterior communicating artery (ACoA) aneurysm rupture. In both cases, the mnestic deficit may be similar when assessed by standard neuropsychological measures. However, animal and computational models suggest that there are qualitative differences in the pattern of impaired and spared memory abilities following damage to hippocampus versus basal forebrain. Here, we show such a dissociation in human amnesia using a single two-stage task, involving conditional discrimination and reversal. Consistent with a prior study, 10 individuals with anterograde amnesia subsequent to hypoxic brain injury were spared on acquisition but impaired at reversal. However, 10 individuals with amnesia subsequent to ACoA aneurysm showed the opposite pattern of impaired acquisition but spared reversal. The differences between groups cannot be easily ascribed to severity of mnestic or cognitive deficit, since the two amnesic groups performed similarly on neuropsychological tests of memory, intelligence and attention. The results illustrate qualitative differences in memory impairments in hypoxic and ACoA amnesics and highlight the importance of considering etiology in evaluating mnemonic deficits in amnesic populations.

Fig. 1

Representative magnetic resonance scans of amnesic participants; all scans shown in the radiologic view (left/right reversal). (A) T1 coronal view through the body of the hippocampus in a representative individual who became amnesic following hypoxic brain injury. There is significant bilateral hippocampal atrophy (arrow points to left hippocampus) and enlargement of the temporal horns of the lateral ventricles. (B) T2 coronal scan of another amnesic individual, whose hypoxic episode resulted in bilateral hippocampal damage (right arrow points to left hippocampus) and extensive enlargement of the temporal horns, cerebral atrophy (left arrow) and ventricular enlargement due to diffuse atrophic changes. (C and D) T2 axial scan of a representative individual who became amnesic following ACoA aneurysm rupture. Right arrow in (C) indicates bilateral damage to basal forebrain and right arrow in (D) shows predominantly left frontal damage. Left arrows in (C) and (D) point to clip artifact.

Fig. 2

Screen events during one trial of the discrimination task. (A) At the start of a trial, an animated rat appears at the bottom of a T-maze and runs up to the choice point and wavers there until the participant presses a key to guide the rat into the left or right maze arm. (C) If the response was correct, a piece of cheese is revealed and a “happy” sound is played and (D) otherwise, there is no cheese and a “sad” sound is played. Placement of cheese on a given trial depends on screen background brightness; here, light gray signals that cheese is available in the right arm, and dark gray signals that cheese is available in the left arm.

Fig. 3

Performance on the conditional discrimination acquisition for all participants, in terms of (A) mean total trials before criterion of eight-in-a-row consecutive correct responses and (B) mean total errors during this phase. Bars represent standard error.

Fig. 4

Performance on the reversal phase, for subjects who completed the acquisition phase, in terms of (A) mean total trials before criterion of eight-in-a-row consecutive correct responses and (B) mean total errors during this phase; (C) shows mean perseverative errors, defined as consecutive incorrect trials immediately following the unsignaled reversal and (D) shows mean number of trials to reacquisition, once subjects stop making perseverative errors. Bars represent standard error.