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

Daniel A Jimenez,Rebecca L Bond,Mai-Carmen Requena-Komuro,Harri Sivasathiaseelan,Charles R Marshall,Lucy L Russell,Caroline Greaves,Katrina M Moore,Ione Oc Woollacott,Rachelle Shafei,Chris Jd Hardy,Jonathan D Rohrer,Jason D Warren

doi:10.1016/j.cortex.2020.05.016

Abstract

IntroductionAbnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised. MethodsWe collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry. Results46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation. ConclusionAltered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally.

Highlights

Fear is an emotion of fundamental biological importance
We have shown that alterations in phobic reactivity are relatively common in major syndromes of frontotemporal dementia (FTD), the behavioural variant, in comparison both to healthy older individuals and patients with Alzheimer’s disease (AD)
While alterations in phobic reactivity were bidirectional across the FTD cohort, development of a new phobia only occurred in patients with a syndrome of FTD

Summary

Introduction

Fear is an emotion of fundamental biological importance. Evolutionarily ancient, it signals danger, directs actions that preserve life and limb and thereby promotes survival. In further contrast to anxiety, fear in undiluted form is rarely experienced by adult humans under ordinary conditions in everyday life - while to engender it deliberately is generally ethically unacceptable. This is a fortunate state of affairs and makes the experience of fear difficult to study experimentally. It presents a pertinent challenge in neurodegenerative diseases, notably the frontotemporal dementias (FTD), in which altered emotion processing is a leading clinical issue and potentially a core pathophysiological principle (Kumfor & Piguet, 2012; C G Lyketsos et al, 2000; Marshall et al, 2019; Rascovsky et al, 2011; Sivasathiaseelan et al, 2019)

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Conclusion