Abstract

ObjectiveTo establish proof‐of‐principle for the use of heart rate responses as objective measures of degraded emotional reactivity across the frontotemporal dementia spectrum, and to demonstrate specific relationships between cardiac autonomic responses and anatomical patterns of neurodegeneration.MethodsThirty‐two patients representing all major frontotemporal dementia syndromes and 19 healthy older controls performed an emotion recognition task, viewing dynamic, naturalistic videos of facial emotions while ECG was recorded. Cardiac reactivity was indexed as the increase in interbeat interval at the onset of facial emotions. Gray matter associations of emotional reactivity were assessed using voxel‐based morphometry of patients’ brain MR images.ResultsRelative to healthy controls, all patient groups had impaired emotion identification, whereas cardiac reactivity was attenuated in those groups with predominant fronto‐insular atrophy (behavioral variant frontotemporal dementia and nonfluent primary progressive aphasia), but preserved in syndromes focused on the anterior temporal lobes (right temporal variant frontotemporal dementia and semantic variant primary progressive aphasia). Impaired cardiac reactivity correlated with gray matter atrophy in a fronto‐cingulo‐insular network that overlapped correlates of cognitive emotion processing.InterpretationAutonomic indices of emotional reactivity dissociate from emotion categorization ability, stratifying frontotemporal dementia syndromes and showing promise as novel biomarkers. Attenuated cardiac responses to the emotions of others suggest a core pathophysiological mechanism for emotional blunting and degraded interpersonal reactivity in these diseases.

Highlights

  • Frontotemporal dementia (FTD) comprises a spectrum of neurodegenerative disorders with three major syndromes[1]; behavioral variant, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia

  • Emotion identification was impaired in all syndromic groups relative to the healthy control group (overall group effect F(4) = 9.7, P < 0.001, g2 = 0.459; bvFTD, rtvFTD, semantic variant primary progressive aphasia (svPPA) all P < 0.001, nonfluent variant primary progressive aphasia (nfvPPA) P = 0.01)

  • Mean heart rate over the entire recording was higher in the nfvPPA group than in healthy controls (P = 0.002)

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Summary

Introduction

Frontotemporal dementia (FTD) comprises a spectrum of neurodegenerative disorders with three major syndromes[1]; behavioral variant (bvFTD), semantic variant primary progressive aphasia (svPPA), and nonfluent variant primary progressive aphasia (nfvPPA). This classification admits considerable heterogeneity; in particular, bvFTD comprises several clinico-anatomical subsyndromes, of which the most distinctive is the variant with predominant right temporal lobe atrophy (right temporal variant; rtvFTD).[2,3] Deficits in emotion processing and empathy are prominent in all FTD syndromes,[4,5] but remain poorly characterized and difficult to quantify. Central to understanding affective empathy is the concept of interoceptive inference, which proposes that emotional awareness entails reciprocal feedback between somatic physiology and the cognitive interpretation of those signals.[8,9] Emotional stimuli produce autonomic effects including modulation of heart rate, but different emotions do not reliably produce specific individual patterns of autonomic responses, and they are hypothesized to relate to arousal and intensity rather than emotion category.[10,11] Stimulus onset induces a cardiac orienting deceleration, which is modulated by affective content, with greater cardiac deceleration accompanying higher emotional valence.[12,13,14] This central regulation of cardiac function is mediated by a distributed brain network including anterior cingulate cortex (ACC), insula, and orbitofrontal cortex (OFC).[15,16] Cardiac afferent information informs affective valuation,[17] and visceral autonomic responses may support emotional contagion and empathy.[9]

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