The functional neuroanatomy of emotion processing in frontotemporal dementias

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.

Keywords: autonomic; cardiac; emotion; frontotemporal dementia; functional MRI.

Figure 1

Functional neuroanatomy of facial emotion viewing: effect of condition. Statistical parametric maps (SPMs) of T contrasts for effect of condition across all participants for early visual processing (visual stimulus > fixation cross contrast; left) and facial emotion processing (contrasts for all facial expressions > dynamic mosaic baseline, positive facial expressions > negative expressions, negative facial expressions > positive expressions) together with a plot (bottom left) of effect sizes (beta-values) demonstrating consistent activation of bilateral primary visual cortex across participant groups (box and whisker plots display median, interquartile range, minimum and maximum values, with outliers appearing as red crosses). SPMs are thresholded at the cluster-defining threshold of P < 0.005 uncorrected and displayed on sections of the structural group mean T₁-weighted template brain image. The plane of each section (in mm in MNI space) is shown in the top right of each image; axial sections show the left hemisphere on the top and the coronal section shows the left hemisphere on the left. The colour bar codes T-values (the same range applies to SPMs in other figures, unless otherwise indicated). bv = patient group with bvFTD; con = healthy control group; nfv = patient group with nfvPPA; sv = patient group with svPPA.

Figure 2

Functional neuroanatomy of facial emotion viewing: effect of participant group. Statistical parametric maps (SPMs) for the F-contrast (main effect of participant group; facial emotion > dynamic mosaic contrast; top row), together with plots of effect sizes (beta-values) demonstrating differential patterns of attenuated BOLD response across groups in the two significant clusters (bottom row; box and whisker plots display median, interquartile range, minimum and maximum values, with outliers appearing as red crosses). SPMs are thresholded at the cluster-defining threshold of P < 0.005 and displayed on sections of the structural group mean T₁-weighted template brain image. The plane of each section (in mm in MNI space) is shown in the top right of each image; the coronal section shows the right hemisphere on the right. bv = patient group with bvFTD; con = healthy control group; FG = fusiform gyrus; MTG = middle temporal gyrus; nfv = patient group with nfvPPA; sv = patient group with svPPA.

Figure 3

Emotion identification: behavioural results and functional neuroanatomy. The figure displays statistical parametric maps (SPMs) for the T-contrast (facial emotion > dynamic mosaic) in each patient group, with score on the post-scanner emotion identification task as predictor variable in order to show the key determinants of identification ability separately within each group (top left, bottom), together with a plot showing performance (per cent correct) on the emotion identification task by participant group (top right; box and whisker plots display median, interquartile range, minimum and maximum values, with outliers appearing as red crosses). SPMs are thresholded at the cluster-defining threshold of P < 0.005 uncorrected (all loci displayed on the sections shown were significant at P_FWE < 0.05 at whole brain or in pre-specified regions of interest (see Table 3 for details) and displayed on sections of the structural group mean T₁-weighted template brain image. The plane of each section (in mm in MNI space) is shown in the top right of each image; the axial section shows the left hemisphere on the left. bv = patient group with bvFTD; con = healthy control group; nfv = patient group with nfvPPA; sv = patient group with svPPA.

Figure 4

Cardiac reactivity: heart rate modulation and functional neuroanatomy. Statistical parametric maps (SPMs) for the T-contrast (facial emotion > dynamic mosaic) in the svPPA and nfvPPA patient groups, with cardiac reactivity as predictor variable. Associations are shown separately for negative correlation with cardiac reactivity (i.e. BOLD signal predicting parasympathetic cardiac deceleration; top row) and positive correlation with cardiac reactivity (i.e. BOLD signal predicting sympathetic cardiac acceleration; bottom row). The plot (top right) shows mean cardiac reactivity (per cent change in heart rate from baseline) to facial expression stimuli by participant group (box and whisker plots display median, interquartile range, minimum and maximum values, with outliers appearing as red crosses). SPMs are thresholded at the cluster-defining threshold of P < 0.005 uncorrected and displayed on sections of the structural group mean T₁-weighted template brain image. The plane of each section (in mm in MNI space) is shown in the top right of each image; axial sections show the right hemisphere on the right. The colour bar codes T-values. bv = patient group with bvFTD; con = healthy control group; nfv = patient group with nfvPPA; sv = patient group with svPPA.

Figure 5

Pupil reactivity: pupil size change and functional neuroanatomy. The figure displays statistical parametric maps (SPMs) for the T-contrast (facial emotion > dynamic mosaic) in the svPPA and nfvPPA patient groups, with pupil reactivity as predictor variable. The plot (bottom right) shows mean pupil reactivity (per cent increase in pupil size from baseline) to facial expression stimuli by participant group (box and whisker plots display median, interquartile range, minimum and maximum values, with outliers appearing as red crosses). SPMs are thresholded at the cluster-defining threshold of P < 0.005 uncorrected and displayed on sections of the structural group mean T₁-weighted template brain image. The plane of each section (in mm in MNI space) is shown in the top right of each image; axial and coronal sections show the left hemisphere on the left. bv = patient group with bvFTD; con = healthy control group; nfv = patient group with nfvPPA; sv = patient group with svPPA.