Elsevier

Neuropsychologia

Volume 46, Issue 8, July 2008, Pages 2152-2160
Neuropsychologia

Defective emotion recognition in early HD is neuropsychologically and anatomically generic

https://doi.org/10.1016/j.neuropsychologia.2008.02.025Get rights and content

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder that classically presents with motor, cognitive and psychiatric symptoms. However, other abnormalities also occur in this condition, notably deficient recognition of facial emotional expressions. Deficits in emotion recognition impact significantly on the lives of HD patients and their families and thus it is important to clarify the onset and pattern of impairment. This study investigated facial emotion recognition in a large cohort of early HD patients, and premanifest gene-carriers. We used voxel-based morphometry (VBM) to examine the neuroanatomical correlates of emotion recognition performance. Forty patients with early HD, 21 premanifest gene carriers and 20 controls were assessed using 24 faces from the Ekman Pictures of Facial Affect, and volumetric brain MRI. The HD group was significantly worse than controls at recognising, surprise, disgust, anger and fear, and worse than the premanifest group at recognising disgust and anger. When patient data were expressed as z-scores, recognition of anger was significantly worse than disgust in the early HD group. In the VBM analysis, these deficits were associated with common regional atrophy: impaired recognition of surprise, disgust, anger and fear were all associated with striatal volume loss. Fear was associated with additional atrophy of the right insula and left and right lateral orbitofrontal cortex.

Even in early HD there is a wide-ranging impairment in recognition of negative emotions denoting ‘threat’. Our findings implicate a generic fronto-subcortical network in the pathogenesis of these emotion recognition deficits.

Introduction

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat on chromosome 4. It is classically characterised by involuntary movements, and cognitive and psychiatric deficits, with the onset of motor signs usually occurring in mid-adulthood, although there is often evidence for subtle cognitive and behavioural deficits ahead of these motor features (Lawrence et al., 1998; Snowden, Craufurd, Thompson, & Neary, 2002). Pathologically HD is characterised by neuronal loss and cerebral atrophy and until recently it was felt that the striatum was selectively targeted in early disease (Aylward et al., 2000) but there is increasing evidence that cortical areas are also affected (Kassubek, Gaus, & Landwehrmeyer, 2004; Rosas et al., 2002). As a result other deficits with a more cortico-striatal basis may be seen in early disease, including emotional processing (Gray, Young, Barker, Curtis, & Gibson, 1997).

Deficits in emotion recognition have been reported in both preclinical (prior to motor onset) and early HD with disgust recognition thought to be particularly impaired (Gray et al., 1997, Sprengelmeyer et al., 1996). This finding has now been replicated (Hennenlotter et al., 2004, Montagne et al., 2006; Sprengelmeyer, Schroeder, Young, & Epplen, 2005; Sprengelmeyer et al., 1997; Wang, Hoosain, Yang, Meng, & Wang, 2003), and has even been found to extend to vocal emotion recognition (Sprengelmeyer et al., 1996) and the olfactory and gustatory domains (Hayes, Stevenson, & Coltheart, 2007; Mitchell, Heims, Neville, & Rickards, 2005).

The presence of focal striatal atrophy in HD (Halliday et al., 1998) led to suggestions that striatal damage might underlie the impairment in disgust recognition, and recently functional and structural imaging studies have found evidence for striatal involvement in recognition of disgust in both visual and auditory modalities (Sprengelmeyer, Rausch, Eysel, & Przuntek, 1998). However, the specificity of this association has not been established. In functional imaging studies the anterior insula is also implicated in recognition of disgust (Hennenlotter et al., 2004; Kipps, Duggins, McCusker, & Calder, 2007; Murphy, Nimmo-Smith, & Lawrence, 2003; Phillips et al., 1997, Phillips et al., 1998, Sprengelmeyer et al., 1998), while striatal activation is also associated with fear recognition (Phillips et al., 1998). These findings suggest that the striatum and insula may jointly participate in processing disgust and other negative emotions. Functional imaging evidence is reinforced both by depth electrode studies of disgust processing (Krolak-Salmon et al., 2003), and by human lesion studies (Calder, Keane, Lawrence, & Manes, 2004; Calder, Keane, Manes, Antoun, & Young, 2000; Calder et al., 1996, Sprengelmeyer et al., 1997).

Furthermore, not all studies have replicated the finding of disproportionately impaired disgust recognition in HD. For example Milders, Crawford, Lamb, and Simpson (2003) looked at facial emotion recognition in a large number of pre- and post-motor onset HD patients and found that whilst post-motor onset patients were impaired at a number of emotions, including disgust, fear was the most severely affected emotion in the post-motor onset group and also in the pre-motor onset group. Recent data from the Predict-HD study has reinforced this, showing that premanifest subjects were impaired at recognition of all negative emotions (sadness, disgust, anger and fear) and showed no evidence of a disproportionate impairment in any one emotion (Johnson et al., 2007). The latter study also pointed out that omitting to adjust for factors such as age and IQ, which were correlated with recognition performance in their cohort, might contribute to differences between studies.

We therefore sought to clarify the emotion recognition deficit in early HD and its brain basis by studying a large, well-defined disease cohort using a range of tasks, including a facial emotion recognition test (Gray et al., 1997). We used voxel-based morphometry (VBM) (Ashburner & Friston, 2000) to look at associations between emotion recognition performance and grey matter atrophy, both across the whole brain and in specific regions of interest (ROI) suggested by previous research. We predicted involvement of a distributed network of structures including the striatum, insula, amygdala and orbitofrontal cortex, as these regions have been widely implicated in emotion recognition both in HD and other disease states and in healthy subjects (Blair, Morris, Frith, Perrett, & Dolan, 1999; Kipps et al., 2007, Sprengelmeyer et al., 1998).

Section snippets

Subjects

Sixty-one patients with genetically confirmed HD were recruited from the multidisciplinary HD clinic at the National Hospital for Neurology and Neurosurgery, London and the Huntington's Disease Clinic at Addenbrooke's Hospital, Cambridge. Forty patients were classified as “early HD” (Shoulson & Fahn, 1979, stages 1 and 2), and 21 patients were gene carriers without motor signs, i.e. “premanifest”. All patients had a CAG repeat length of >39. Twenty neurologically normal controls, who comprised

Results

Demographic data are shown in Table 1. Differences in gender, handedness and IQ were small and non-significant. The premanifest group was on average significantly younger than the healthy control group (t = 2.59, p = 0.011) and the early HD group (t = 4.43, p < 0.0001).

Discussion

Here we present evidence for impaired recognition of negative facial emotions in a well-characterised cohort of 40 patients with early HD. Our early stage non-depressed, non-demented HD patients were significantly worse than healthy subjects at recognising facial expressions of anger, disgust, fear and surprise, and significantly worse at recognising anger than disgust or fear. Although there was no evidence of significant deficits in individuals with premanifest HD, for all emotions other than

Acknowledgements

The authors would like to thank the patients and controls who took part in this study. They would also like to acknowledge Dr Rohani Omar for useful discussion and help creating ROIs, and Ms Jo Foster for providing the amygdala segmentation. We are grateful to the reviewers, whose comments were extremely helpful in improving the manuscript. This work was funded by the High Q Foundation. GRR is funded by an EPSRC CASE Studentship, sponsored by GlaxoSmithKline. RIS and NCF are funded by the MRC.

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