Functional neuroanatomy of musical object processing in Alzheimer's disease and frontotemporal dementia

Music, besides its emotional and social resonance, models a complex sensory environment exemplifying auditory objects corresponding to sources (musical instruments) and information streams (melodies). These musical dimensions can be variably preserved or blighted by neurodegenerative disease. Music is, therefore, an attractive way to investigate the neural mechanisms of sensory object processing in these diseases. Here, we assessed the functional neuroanatomy underlying the perceptual, semantic, and apperceptive processing of musical objects in Alzheimer's disease and temporal variant frontotemporal dementia. We studied 35 patients (20 Alzheimer's disease, 15 temporal variant frontotemporal dementia; 14 females; mean [standard deviation] age 70.3 [8.4] years) in relation to 25 cognitively healthy volunteers (16 females; age 69.5 [6.8] years). In a functional MRI experiment with sparse image acquisition to minimise the impact of scanner noise, participants passively listened to monophonic melodies. We varied timbre (same/change), timbre familiarity (natural/artificial instruments), melody familiarity (familiar/novel), and apperception (melodies with interpolated timbre changes); these manipulations allowed us to assess the functional neuroanatomical correlates of musical feature perception, melody familiarity, constancy, novelty, and instrument familiarity. Behavioural correlates were assessed in post-scan tasks and disease-related atrophy patterns using voxel-based morphometry of participants' structural scans. All contrasts were assessed at P < 0.05, corrected for multiple voxel-wise comparisons within pre-specified anatomical regions of interest. For timbre change perception, all participant groups demonstrated comparable temporo-parietal cortical activation anchored in planum temporale. For melodies, processing of semantic familiarity in all participant groups engaged a common network including supplementary motor area and inferior frontal gyrus, with reduced supplementary motor area activation in the Alzheimer's disease group compared with other groups, while melody novelty comparably engaged postero-medial cortical circuitry across groups. Apperceptive coding of melody constancy was associated with activation of the posterior superior temporal cortex in the healthy volunteers, but greater activation of the temporal polar cortex in the temporal variant frontotemporal dementia group than in healthy volunteers. For instrument familiarity, the temporal variant frontotemporal dementia group showed reduced activation of the temporal polar cortex, but increased activation of the anterior insula compared to healthy volunteers. Brain activation profiles were not influenced by behavioural performance on post-scan tasks and did not coincide with regional atrophy. Our findings delineate complex, differentiated functional neuroanatomical profiles of musical object processing in Alzheimer's disease and frontotemporal dementia, with implications for our understanding of the neural mechanisms that decode complex sensory environments and the design and evaluation of interventions in these diseases.