Music processing in behavioural variant frontotemporal dementia and Alzheimer’s disease: a functional MRI study

Abstract Music engages brain regions involved in perceptual, socio-emotional and cognitive functions that may be relatively preserved in individuals with Alzheimer's disease but seem affected early in behavioural variant frontotemporal dementia. The effects of music in dementia are often assessed through observational studies, leaving the neurophysiological underpinnings of music processing in these dementia types unclear. Improved understanding of these mechanisms is relevant because the effectiveness of music therapy may depend on dementia types. In this study we investigated whether patients with behavioural variant frontotemporal dementia and Alzheimer’s disease differ in music processing compared to healthy controls. We studied 60 participants (n=35 female; aged 52-81), including 13 patients with behavioural variant frontotemporal dementia, 22 patients Alzheimer's disease, and 25 healthy controls. We designed a novel functional MRI paradigm based on passive listening to self-selected favourite music and experimenter-selected unfamiliar musical pieces using a sparse-sampling design. Activation patterns of favourite music listening (favourite > silence), unfamiliar music listening (unfamiliar > silence), and favourite music more than unfamiliar music (favourite > unfamiliar) were determined for each participant. Next, we compared activation patterns across groups for each contrast. Finally, associations between activation patterns and disease severity were investigated in behavioural variant frontotemporal dementia and Alzheimer’s disease separately. The patient groups exhibited typical neuropsychological, socio-emotional and structural anatomical changes associated with Alzheimer’s disease and behavioural variant frontotemporal dementia. Patients with behavioural variant frontotemporal dementia showed overall less activation during favourite music listening compared to Alzheimer’s disease and healthy controls. When contrasting favourite and unfamiliar music, we found that patients with behavioural variant frontotemporal dementia showed reduced activation in the supplementary motor area, a region that has previously been implicated as an important region for semantic musical memory. Increased connectivity of the auditory cortices was observed in behavioural variant frontotemporal dementia compared to controls, potentially indicating network immaturity. Only patients with Alzheimer’s disease exhibited activation in the caudate nucleus during unfamiliar music, a region associated with musical reward processing. Disease severity in Alzheimer’s disease and behavioural variant frontotemporal dementia were associated with distinct patterns of functional activation. Our results confirm and expand the observation that music is processed differently in patients with behavioural variant frontotemporal dementia and Alzheimer's disease. The reduced activation in the supplementary motor area may explain altered music processing in behavioural variant frontotemporal dementia. These differences in music processing could have clinical implications in the selection of music therapy.