Furthermore, it is necessary to sample a wide range of stimuli and behaviours, as alterations of affective processing in neurodegenerative diseases may extend to categories of stimuli that lack primary biological reward value. Besides neuropsychological and psychophysical procedures, a complete characterisation of affective responses in patients with dementia requires detailed analysis of output behaviours, particularly those signalling pleasure or aversion. This reflects the inherently complex organisation of emotional behaviour, which is often only partly accessible to explicit cognitive decoding and relies intimately on subjective states of emotional awareness or affect. In contrast to the better characterised phenotypes of language, perceptual and executive impairment, phenotypes of altered emotional responsiveness are difficult to capture using standard neuropsychological instruments and remain poorly defined in the dementias. This phenotypic overlap reflects the involvement in these diseases of distributed fronto-temporal, parietal and subcortical circuitry previously implicated in the representation, decoding and evaluation of salient stimuli ( Sescousse, Caldu, Segura, & Dreher, 2013). However, emotional disturbances may also be significant in other FTLD syndromes such as progressive nonfluent aphasia (PNFA) ( Kumfor et al., 2011 Rohrer & Warren, 2011 Rohrer, Sauter, Scott, Rossor, & Warren, 2012) and with other neurodegenerative pathologies, notably Alzheimer's disease (AD) ( Sturm et al., 2013). Altered emotional responses are a hallmark of diseases in the frontotemporal lobar degeneration (FTLD) spectrum, particularly in association with the syndromes led by behavioural disintegration (behavioural variant frontotemporal dementia, bvFTD) and semantic disintegration (semantic dementia, SD) ( Duval et al., 2012 Hodges & Patterson, 2007 Rankin et al., 2009 Rohrer & Warren, 2010 Snowden et al., 2001). From a neurobiological perspective, such dysfunction illuminates critical neural mechanisms mediated by brain networks that are targeted by neurodegenerative pathologies ( Zhou & Seeley, 2014).
From a clinical perspective, emotional dysregulation is likely to contribute to a wide spectrum of symptoms that impact the lives of patients and their caregivers: examples range from abnormal responses to thermoregulatory and other basic homeostatic signals ( Ahmed et al., 2014) to pathological seeking of rewarding stimuli such as food, sex or drugs ( Perry et al., 2014 Whitwell et al., 2007 Woolley et al., 2007) and derangements of complex social behaviours ( Clark, Downey, Golden, et al., 2014 Mahoney, Rohrer, Omar, Rossor, & Warren, 2011 Sturm et al., 2013). Sounds may constitute a novel probe of brain mechanisms for emotional salience coding that are targeted by neurodegenerative disease.Īltered emotional responsiveness to salient sensory stimuli is a key issue in neurodegenerative diseases. Our findings suggest that abnormalities of auditory hedonic processing are a significant issue in common dementias. Auditory hedonic alterations correlated with grey matter loss in a common, distributed, right-lateralised network including antero-mesial temporal lobe, insula, anterior cingulate and nucleus accumbens. Aversion to sounds was the exclusive auditory phenotype in AD whereas more complex phenotypes including musicophilia were common in bvFTD and SD. Behavioural responses signalling abnormal aversion to environmental sounds, aversion to music or heightened pleasure in music (‘musicophilia’) occurred in around half of the cohort but showed clear syndromic and genetic segregation, occurring in most patients with bvFTD but infrequently in PNFA and more commonly in association with MAPT than C9orf72 mutations. Here we addressed this issue in a cohort of 73 patients representing major canonical dementia syndromes (behavioural variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA) amnestic Alzheimer's disease (AD)) using a semi-structured caregiver behavioural questionnaire and voxel-based morphometry (VBM) of patients' brain MR images. Patients with dementia may exhibit abnormally altered liking for environmental sounds and music but such altered auditory hedonic responses have not been studied systematically.