Abstract
J Physiol. 2025 Oct 19. doi: 10.1113/JP288693. Online ahead of print.
ABSTRACT
We have recently shown that perception of uprightness is disturbed in typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA; 'visual-variant Alzheimer's'); disturbances were attributed to disrupted spatial transformation of graviceptive information. Here, we extend investigations to the vestibular control of uprightness during stance using galvanic vestibular stimulation (GVS) under various proprioceptive and visual conditions. An appropriately directed response to GVS requires spatial transformation of the vestibular signal based on head orientation relative to the feet, while non-vestibular sensory information can modulate the magnitude of response. Balance responses were repeatedly evoked in healthy participants (n = 21) and participants with AD (tAD: n = 18; PCA: n = 18) under conditions evaluating proprioceptive-vestibular integration (head directed right, straight or left without vision), or visuo-vestibular integration (head directed straight with or without vision). Across head directions without vision, GVS-evoked response direction and magnitude were comparable across groups. These comparable responses without vision indicate sparing of vestibulo-motor systems and proprioceptive-vestibular integration predicated on transformations between head, body and leg coordinates. However, the modulating effect of vision on GVS-evoked response magnitude was decreased in PCA relative to control and tAD groups. This relatively decreased effect of vision in PCA was evident through the earliest mechanical indicator of response, consistent with reduced feedforward effects of vision on vestibularly driven balance response. Exaggerated response magnitude with vision was associated with occipito-thalamic volumetric and projection fibre abnormalities in PCA. The findings suggest candidate pathways for visual modulation of vestibular balance control and dissociations between systems responsible for perceiving uprightness versus rapid sensorimotor balance control. KEY POINTS: Accurate balance control relies on the integration of vestibular, proprioceptive and visual inputs, transformed across spatial reference frames. We examined whole-body balance responses to galvanic vestibular stimulation (GVS) under varying visual and proprioceptive conditions in people with posterior cortical atrophy (PCA), typical Alzheimer's disease (tAD) and controls. Without vision, GVS-evoked balance responses were comparable across groups with the head turned left, right or straight ahead, indicating spared proprioceptive-vestibular integration in patient groups. With vision, visual input had a reduced modulatory effect on GVS responses in PCA relative to tAD and control groups. This was evident at the earliest stage of mechanical response, suggesting reduced feedforward visual influences on balance control in PCA. Our findings implicate disrupted occipito-thalamic pathways in PCA-related balance disturbances. The findings reveal a dissociation between perceived uprightness and sensorimotor balance control, with implications for understanding disturbed spatial orientation and balance in dementia.
PMID:41110946 | DOI:10.1113/JP288693