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Path Integration in Alzheimer's Disease: Orientation, Movement, and Theta Rhythmicity
Andrea Castegnaro1,2, Misun Kim1,2, Katarzyna Rudzka1
1UCL Institute of Cognitive Neuroscience, University College London, London, United Kingdom; email: andrea.castegnaro.15@ucl.ac.uk, misun.kim@ucl.ac.uk, n.burgess@ucl.ac.uk.
Annual Review of Neuroscience
|April 16, 2026
Summary
Path integration, crucial for navigation and an Alzheimer's marker, involves a circuit beyond grid cells. Early Alzheimer's impacts this circuit, affecting orientation and movement direction signals.
Area of Science:
- Neuroscience
- Cognitive Science
- Pathology
Background:
- Path integration (PI) is a key cognitive function for spatial navigation and orientation.
- PI is a sensitive early marker for Alzheimer's disease (AD).
- While entorhinal grid cells are known contributors, the broader circuit is less understood.
Purpose of the Study:
- To investigate the functional circuit supporting path integration.
- To explore the impact of Alzheimer's disease on this circuit.
- To identify specific circuit components vulnerable in early AD.
Main Methods:
- Focus on the broader functional circuit of PI, including head direction cells, landmark-based correction, and movement direction signals.
- Hypothesize roles for theta-modulated cells and theta sweeps in grid and place cells.
- Consider potential circuit disruptions in AD, such as thalamic pathology and cholinergic dysfunction.
Main Results:
- Early vulnerability of PI, especially angular PI, in AD.
- Potential degradation of head direction coding due to anterodorsal thalamus pathology.
- Disrupted theta rhythmicity affecting directional signals, possibly due to cholinergic dysfunction.
- Retrosplenial failures in landmark resetting contributing to angular drift.
Conclusions:
- PI impairment in AD likely stems from multiple circuit failures.
- Early AD affects orientation and movement direction processing within the PI circuit.
- Cross-species electrophysiological studies are needed to elucidate PI mechanisms and AD-related impairments.
Keywords:
Alzheimer's diagnosisangular path integrationcholinergic modulationdementiahead directiontheta rhythmMore Related Videos
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