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Scopolamine disrupts hippocampal activity during allocentric spatial memory in humans: an fMRI study using a virtual
Elena Antonova1, David Parslow, Michael Brammer
1Department of Psychology, King's College London, Institute of Psychiatry, London, UK. elena.antonova@kcl.ac.uk
Abstract:
The role of the septohippocampal cholinergic system in memory disorders is well established. The effects of cholinergic challenge in animals have been extensively studied using the Morris Water Maze (MWM) which engages allocentric spatial memory. The present study investigated the effect of the centrally active muscarinic antagonist scopolamine on allocentric spatial memory in humans using a virtual reality analogue of the MWM task, the Arena task. Twenty right-handed healthy male adults with a mean age of 28 years (range 23-35 years) were studied using functional MRI in a randomized double-blind cross-over design with scopolamine bromide (0.4 mg i.m.) or placebo (saline) administered 70-90 min before the beginning of the functional scan. Scopolamine induced a significant reduction in the activation of the hippocampus/parahippocampal gyrus compared with placebo. Furthermore, there was dissociation between hippocampus-based and striatal-based memory systems, which were significantly more activated in the placebo and scopolamine conditions, respectively. The activation of the striatal system under scopolamine challenge was accompanied by the activation of the amygdala. In conclusion, the study extends the well-documented finding in animals of the attenuating effect of scopolamine on hippocampal activity during allocentric spatial memory to humans. Furthermore, the results call for further investigation of the dissociation between the hippocampal and neostriatal memory systems during allocentric spatial processing under cholinergic blockade in humans.
Insights
Scopolamine, a drug affecting memory, reduced hippocampal activity in humans during a spatial memory task. This suggests a dissociation between hippocampal and striatal memory systems under cholinergic blockade.
Area of Science:
- Neuroscience
- Cognitive Psychology
- Pharmacology
Background:
- The septohippocampal cholinergic system is crucial for memory, with its role in disorders well-established.
- Animal studies extensively use the Morris Water Maze (MWM) to assess allocentric spatial memory under cholinergic challenge.
- Scopolamine is a centrally active muscarinic antagonist known to impair memory.
Purpose of the Study:
- To investigate the effect of scopolamine on human allocentric spatial memory.
- To examine brain activation patterns during a virtual reality spatial memory task under scopolamine versus placebo.
- To explore the dissociation between memory systems under cholinergic blockade.
Main Methods:
- A virtual reality analogue of the MWM, the Arena task, was employed.
- Twenty healthy adult males participated in a randomized, double-blind, cross-over study.
- Functional MRI was used to measure brain activity after administration of scopolamine bromide (0.4 mg i.m.) or placebo.
Main Results:
- Scopolamine significantly reduced activation in the hippocampus/parahippocampal gyrus compared to placebo.
- A dissociation was observed between hippocampus-based and striatal-based memory systems.
- The striatal system showed increased activation under scopolamine, accompanied by amygdala activation.
Conclusions:
- The study confirms scopolamine's attenuating effect on hippocampal activity during allocentric spatial memory in humans, extending findings from animal models.
- Results suggest a functional dissociation between hippocampal and neostriatal memory systems under cholinergic blockade in humans.
- Further research is warranted to investigate this dissociation during allocentric spatial processing.
