Path Integration in Alzheimer's Disease: Orientation, Movement, and Theta Rhythmicity
Year: 2026
Type: review
Abstract: Path integration (PI), the ability to keep track of position and orientation from self-motion, is a sensitive cognitive marker of Alzheimer's disease. While entorhinal grid cells are central to PI, we focus here on the broader functional circuit supporting PI and the impact of Alzheimer's disease within it. This circuit includes orientation from head direction cells, landmark-based error correction, and signals encoding current or intended movement direction, which we suggest may rely on theta-modulated directional cells and theta sweeps in grid and place cell firing. The early vulnerability of PI, particularly angular PI, may reflect multiple sources: pathology in the anterodorsal thalamus degrading head direction coding; disrupted theta rhythmicity and thus theta-modulated directional signals, potentially reflecting cholinergic dysfunction; and retrosplenial landmark-resetting failures allowing angular drift. We advocate for further cross-species investigation of PI tasks with electrophysiological measures to fully identify the underlying circuit mechanisms and their impairment in Alzheimer's disease.
Source: Annual Review of Neuroscience
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7154644967
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