MUSIC AND UNDERLYING BRAIN FUNCTION IN PERSONS WITH DEMENTIA

Abstract

There is currently considerable interest in music as a focus of preserved capacity in dementia. However, in addition to its place as an art form and balm for distress, music has unique informational and cognitive attributes that make it well suited as a probe of pathophysiology in neurodegenerative brain diseases. Here I describe recent work that uses music to characterise functional neuroanatomical profiles of disordered information processing in the large-scale brain networks targeted by Alzheimer's disease and frontotemporal dementias. We studied cohorts of patients with defined or highly predictable molecular pathologies: Alzheimer's disease (typical amnestic, posterior cortical and logopenic variants) and syndromes of semantic dementia and genetically mediated behavioural variant frontotemporal dementia (MAPT and C9orf72 mutations). In a functional MRI paradigm based on passive listening to melodies, we manipulated stimulus dimensions designed to engage core perceptual and cognitive processes: rhythm (temporal coding), melodic familiarity (semantic memory) and melodic repetition (episodic memory). Cerebral activation profiles in patients were referenced to a healthy older control group. We identified separable profiles of altered brain network function in neurodegenerative pathologies relative to healthy controls. Rhythm processing was associated with dysfunction of a fronto-temporal network in TDP pathologies (semantic dementia, C9orf72 mutations). Semantic processing of melodies was associated with dysfunction of mesial temporal lobe in MAPT mutations and insula and postero-medial cortex in logopenic aphasia. Episodic memory for melodies was associated with dysfunction of postero-medial cortex in both typical amnestic Alzheimer's disease and posterior cortical atrophy. Disease-associated response profiles were complex, including both reduced and abnormally enhanced activation to particular musical dimensions. These findings suggest that music can differentiate functional neuroanatomical phenotypes of molecular pathologies underpinning major dementias. Further work is needed to validate this promise in larger patient cohorts with pathological correlation. Effective treatments for dementia may depend on the identification of new disease markers that can link molecular pathology with neural network disintegration and complex symptoms of social and emotional dysfunction: music may be a novel tool to achieve this.