A physiological signature of sound meaning in dementia.

The meaning of sensory objects is often behaviourally and biologically salient and decoding of semantic salience is potentially vulnerable in dementia. However, it remains unclear how sensory semantic processing is linked to physiological mechanisms for coding object salience and how that linkage is affected by neurodegenerative diseases. Here we addressed this issue using the paradigm of complex sounds. We used pupillometry to compare physiological responses to real versus synthetic nonverbal sounds in patients with canonical dementia syndromes (behavioural variant frontotemporal dementia - bvFTD, semantic dementia - SD; progressive nonfluent aphasia - PNFA; typical Alzheimer's disease - AD) relative to healthy older individuals. Nonverbal auditory semantic competence was assessed using a novel within-modality sound classification task and neuroanatomical associations of pupillary responses were assessed using voxel-based morphometry (VBM) of patients' brain MR images. After taking affective stimulus factors into account, patients with SD and AD showed significantly increased pupil responses to real versus synthetic sounds relative to healthy controls. The bvFTD, SD and AD groups had a nonverbal auditory semantic deficit relative to healthy controls and nonverbal auditory semantic performance was inversely correlated with the magnitude of the enhanced pupil response to real versus synthetic sounds across the patient cohort. A region of interest analysis demonstrated neuroanatomical associations of overall pupil reactivity and differential pupil reactivity to sound semantic content in superior colliculus and left anterior temporal cortex respectively. Our findings suggest that autonomic coding of auditory semantic ambiguity in the setting of a damaged semantic system may constitute a novel physiological signature of neurodegenerative diseases.