Fronto-parietal contributions to episodic retrieval-evidence from neurodegenerative disorders

Converging evidence suggests a critical role for the parietal cortices in episodic memory retrieval. Here, we examined episodic memory performance in Corticobasal Syndrome (CBS), a rare neurodegenerative disorder presenting with early parietal atrophy in the context of variable medial temporal lobe damage. Forty-four CBS patients were contrasted with 29 typical Alzheimer's disease (AD), 29 healthy Controls, and 20 progressive supranuclear palsy patients presenting with brainstem atrophy as a disease control group. Participants completed standardized assessments of verbal episodic memory (learning, delayed recall, and recognition), and underwent structural and diffusion-weighted MRI. Selective delayed recall deficits were evident in the CBS group relative to Controls, at an intermediate level to the stark amnesia displayed by AD, and Control-level performance noted in progressive supranuclear palsy. Considerable variability within the CBS group on delayed recall performance led to the identification of memory-spared (N = 19) and memory-impaired (N = 25) subgroups. Whereas CBS-Spared showed no significant memory deficits, the CBS-Impaired subgroup were indistinguishable from typical AD across all episodic memory measures. Whole-brain voxel-based morphometry analyses implicated fronto-parietal and medial temporal regions in delayed recall performance in both the CBS-Impaired and AD groups. Furthermore, diffusion tensor imaging analyses revealed correlations between delayed recall performance and altered structural connectivity between fronto-parietal and frontotemporal regions in the CBS-Impaired group. Our findings underscore the importance of a distributed brain network including frontal, medial temporal, and parietal brain regions in supporting the capacity for successful episodic memory retrieval.