Cardiac responses to viewing facial emotion differentiate frontotemporal dementias

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.

The functional neuroanatomy of emotion processing in frontotemporal dementias

“…Autonomic reactivity to viewing facial emotions in health engages both visual association areas and the central autonomic control network, including anterior cingulate and insula ( Critchley et al , 2005 ). Targeting of similar brain networks by the proteinopathies of FTD leads, predictably, to diverse socio-emotional symptoms: deficits of face recognition, emotional categorization, motoric and autonomic reactivity and emotional theory of mind have all been demonstrated in FTD and attributed to regional grey matter loss in distributed fronto-temporo-parietal circuitry ( Rosen et al , 2002 ; Kipps and Hodges, 2006 ; Omar et al , 2011 a , b ; Rohrer et al , 2012 ; Couto et al , 2013 ; Downey et al , 2013 ; Oliver et al , 2015 ; Hazelton et al , 2016 ; Hutchings et al , 2017 ; Marshall et al , 2018 a , b ). However, the pathophysiological mechanisms that translate neural circuit disintegration to complex socio-emotional phenotypes in these diseases have not been examined directly.…”

Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis

“…The pathophysiological mechanisms that mediate phobic alterations will only be fully delineated by functional neuroimaging techniques that can examine large-scale brain network connectivity changes and by correlation with autonomic responses. The latter will be particularly pertinent in FTD, in which abnormal physiological processing of sensory signals ( Marshall, Hardy, Allen, et al., 2018 ; Marshall, Hardy, Russell, et al., 2018 ; Marshall et al., 2017 ) and abnormal fear conditioning ( Hoefer et al., 2008 ) have emerged as significant issues that could clearly affect the subjective experience of fear in these patients. Besides abnormal salience coding, there are potentially several other, non-exclusive candidate mechansisms that could lead to altered phobic responses (including, for example, impaired understanding of phobic objects, and loss of insight into the nature and appropriateness of one's own fear response).…”

“…Multimodal impairments of emotion decoding and homeostatic signal processing underpinned by fronto-temporo-limbic circuit dysfunction are increasingly recognised in FTD and may contribute to loss of empathy and aberrant socio-emotional reactivity ( Farb et al., 2013 ; Kumfor & Piguet, 2012 ; Marshall, Hardy, Allen, et al., 2018 ; Marshall et al., 2017 , 2019 ; Marshall, Hardy, Russell, et al., 2018 ; Omar et al., 2011 ). In Alzheimer's disease (AD), emotion processing deficits tend to be less prominent but are increasingly also recognised even at earlier disease stages and adversely affect clinical outcomes ( Barnes et al., 2015 ; Lyketsos et al., 2011 ).…”

Frontotemporal Dementia: A Clinical Review

“…In addition, there is growing awareness of the systemic metabolic and physiological correlates of deranged homeostatic processing in FTD. 91,92 Complementary tools derived from functional neuroimaging, autonomic, and electrophysiology 39,53,88,93 address neural network dysfunction and may yield proxies of complex clinical phenotypes that are difficult to measure directly. Multimodal biomarkers combining these different measures may provide the most sensitive and specific pathophysiological indices of underlying pathogenic protein activity.…”

“…C9orf72associated FTD could be considered a "molecular nexopathy": a coherent conjunction of pathogenic protein, neural network, and clinical phenotype. 35 Deconstruction of other complex phenotypes within the FTD spectrum and identification of specific physiological markers may allow analogous linkages to be established for a range of pathogenic proteins; abnormal physiological coding of internal and externally generated emotional signals is richly differentiated across the FTD spectrum 53,55,93,105 and may yield quantifiable proxies of socioemotional behavioral disturbances that are difficult to measure directly.…”