The functional neuroanatomy of emotion processing in frontotemporal dementias.
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.
['Marshall|Charles R|CR|', 'Hardy|Christopher J D|CJD|', 'Russell|Lucy L|LL|', 'Bond|Rebecca L|RL|', 'Sivasathiaseelan|Harri|H|', 'Greaves|Caroline|C|', 'Moore|Katrina M|KM|', 'Agustus|Jennifer L|JL|', 'van Leeuwen|Janneke E P|JEP|', 'Wastling|Stephen J|SJ|', 'Rohrer|Jonathan D|JD|', 'Kilner|James M|JM|', 'Warren|Jason D|JD|']
D000342:Affective Symptoms D000368:Aged D018888:Aphasia, Primary Progressive D001341:Autonomic Nervous System D001931:Brain Mapping D004644:Emotions D005149:Facial Expression D005260:Female D057180:Frontotemporal Dementia D006339:Heart Rate D006801:Humans D008032:Limbic System D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D009415:Nerve Net D009483:Neuropsychological Tests D011680:Pupil
emotion frontotemporal dementia functional MRI autonomic cardiac