A physiological signature of sound meaning in dementia

Phillip D Fletcher,Jennifer M Nicholas,Laura E Downey,Hannah L Golden,Camilla N Clark,Carolina Pires,Jennifer L Agustus,Catherine J Mummery,Jonathan M Schott,Jonathan D Rohrer,Sebastian J Crutch,Jason D Warren

doi:10.1016/j.cortex.2016.01.007

Phillip D Fletcher, Jennifer M Nicholas + Show 10 more

Open Access

https://doi.org/10.1016/j.cortex.2016.01.007

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Abstract

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.

Highlights

Disambiguation of potentially relevant, ‘salient’ stimuli from the busy multisensory background is accomplished efficiently and largely automatically by the healthy brain
We have demonstrated that dementia syndromes have different profiles of autonomic responses to real and synthetic nonverbal sounds, after controlling for elementary acoustic and affective factors
The magnitude of the differential response was inversely related to auditory nonverbal cortex 7 7 ( 2 0 1 6 ) 1 3 e2 3 semantic competence across dementia syndromes but was not related to overall autonomic reactivity, more general disease severity or medication effects

Summary

Introduction

Disambiguation of potentially relevant, ‘salient’ stimuli from the busy multisensory background is accomplished efficiently and largely automatically by the healthy brain. Successful processing of sensory salience depends on a number of subprocesses: these include accurate parsing of the sensory environment, representation of particular sensory objects, assignment of emotional and reward value, and linkage to physiological and motor effector mechanisms that govern an appropriate behavioural response (Beissner, Meissner, Bar, & Napadow, 2013; Critchley, Corfield, Chandler, Mathias, & Dolan, 2000; Kirsch, Boucsein, & Baltissen, 1995; Zhou & Seeley, 2014). Such abnormalities further suggest a physiological substrate for the higher order disturbances of emotional and social cognition that frequently accompany these diseases (Downey et al, 2015; Kumfor & Piguet, 2012; Omar et al, 2011; Warren, Rohrer, & Rossor, 2013; Woolley et al, 2015), with implications for biomarker development and management strategies

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