Abstract
Impaired processing of emotional signals is a core feature of frontotemporal dementia syndromes, but the underlying neural mechanisms have proved challenging to characterize and measure. Progress in this field may depend on detecting functional changes in the working brain, and disentangling components of emotion processing that include sensory decoding, emotion categorization and emotional contagion. We addressed this using functional MRI of naturalistic, dynamic facial emotion processing with concurrent indices of autonomic arousal, in a cohort of patients representing all major frontotemporal dementia syndromes relative to healthy age-matched individuals. Seventeen patients with behavioural variant frontotemporal dementia [four female; mean (standard deviation) age 64.8 (6.8) years], 12 with semantic variant primary progressive aphasia [four female; 66.9 (7.0) years], nine with non-fluent variant primary progressive aphasia [five female; 67.4 (8.1) years] and 22 healthy controls [12 female; 68.6 (6.8) years] passively viewed videos of universal facial expressions during functional MRI acquisition, with simultaneous heart rate and pupillometric recordings; emotion identification accuracy was assessed in a post-scan behavioural task. Relative to healthy controls, patient groups showed significant impairments (analysis of variance models, all P < 0.05) of facial emotion identification (all syndromes) and cardiac (all syndromes) and pupillary (non-fluent variant only) reactivity. Group-level functional neuroanatomical changes were assessed using statistical parametric mapping, thresholded at P < 0.05 after correction for multiple comparisons over the whole brain or within pre-specified regions of interest. In response to viewing facial expressions, all participant groups showed comparable activation of primary visual cortex while patient groups showed differential hypo-activation of fusiform and posterior temporo-occipital junctional cortices. Bi-hemispheric, syndrome-specific activations predicting facial emotion identification performance were identified (behavioural variant, anterior insula and caudate; semantic variant, anterior temporal cortex; non-fluent variant, frontal operculum). The semantic and non-fluent variant groups additionally showed complex profiles of central parasympathetic and sympathetic autonomic involvement that overlapped signatures of emotional visual and categorization processing and extended (in the non-fluent group) to brainstem effector pathways. These findings open a window on the functional cerebral mechanisms underpinning complex socio-emotional phenotypes of frontotemporal dementia, with implications for novel physiological biomarker development.
Highlights
Impaired responses to emotional signals are a striking feature of the frontotemporal dementias (FTD) and profoundly disrupt social functioning in these diseases (Rohrer et al, 2012; Hsieh et al, 2013; Warren et al, 2013a; Marshall et al, 2018c)
Performance data for the post-scan emotion identification task are presented in Table 1 and Figure 3
Our findings extend previous work in behavioural variant of FTD (bvFTD) (Virani et al, 2013; De Winter et al, 2016), demonstrating that Nonfluent variant primary progressive aphasia (nfvPPA) is associated with reduced engagement of the temporo-occipital hub for dynamic facial expression processing while all major FTD syndromes lead to reduced activity in fusiform face-responsive cortex
Summary
Impaired responses to emotional signals are a striking feature of the frontotemporal dementias (FTD) and profoundly disrupt social functioning in these diseases (Rohrer et al, 2012; Hsieh et al, 2013; Warren et al, 2013a; Marshall et al, 2018c). In the healthy brain, processing of socio-emotional signals such as facial expressions engages four principal, large-scale and hierarchically organised neural networks (Alcalá-López et al, 2017): a ‘visual-sensory’ network of face and biological motion-responsive areas, mediating analysis of stimulus features; a ‘limbic’ network of mesial temporal and ventromedial prefrontal structures, mediating affective valuation of stimuli; an ‘intermediate’ fronto-parietal and cingulo-insular network, integrating salient environmental and bodily states; and a ‘higher associative’ network of temporo-parietal junctional, temporal polar and dorsomedial prefrontal cortices, engaged in interpreting and responding to mental states. The pathophysiological mechanisms that translate neural circuit disintegration to complex socioemotional phenotypes in these diseases have not been examined directly
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