Emotion Evaluation and Social Inference Impairments in Huntington’s Disease

Abstract

Background: Huntington’s disease (HD) is an inherited neurodegenerative disorder characterised by motor, cognitive and neuropsychiatric symptoms. Recent research has established that individuals with HD display reduced discrimination of emotional facial expressions and impaired higher-order social cognitive skills, including ‘theory of mind’.

Objective: This study aimed to further characterise the emotion evaluation and theory of mind deficits in HD in an ecologically-valid context, and determine their impact on socially-relevant functional abilities.

Methods: A sample of 17 HD participants and 24 healthy controls were assessed using The Awareness of Social Inference Test (TASIT), together with additional self- and informant rated measures of cognition, social communication, empathy and neuropsychiatric symptoms.

Results: Participants with HD showed significant difficulties in evaluating negative emotions, and understanding sincere, sarcastic and ‘paradoxical sarcastic’ statements, compared with controls. The ability to evaluate positive emotions was negatively correlated with behavioural problems, but no other clinical, behavioural or communication measures correlated significantly with TASIT subscales.

Conclusions: These findings suggest that social cognitive difficulties in symptomatic HD may be underpinned by more generalised impairments, related to deciphering social exchanges, as opposed to a selective theory of mind deficit. Such difficulties have the potential to place significant strain on interpersonal relationships, and thus warrant thorough clinical assessment, using ecologically-valid tools, to promote early detection and development of person-centred interventions.

Keywords

Social cognition theory of mind TASIT emotion recognition sarcasm executive function social communication empathy clinical assessment

INTRODUCTION

Huntington’s disease (HD) is an inherited neurodegenerative disorder associated with progressive motor, cognitive and psychiatric decline. Clinical onset of symptomatic HD is currently defined by hallmark motor symptoms [1]. However, research has consistently established that cognitive, mood and behavioural signs emerge in “premanifest” disease stages [2], as do structural and functional brain changes in numerous cortical and subcortical regions [3]. Due to the dysfunction of frontostriatal circuitry, cognitive changes in symptomatic HD stages typically comprise attentional and executive-mediated deficits, together with declines in memory and communication. Despite decades of research characterising such deficits, comparatively less is known about the more complex neuropsychiatric and social cognitive deficits arising from disturbances to cortico-subcortical circuits not tapped by traditional neuropsychological tests, such as the ventromedial prefrontal cortex [4].

Social cognition encompasses how individuals perceive and respond to social situations. This domain is known to be affected in many neurological conditions due to the disruption of prefrontal, particularly ventromedial, circuits [5]. Two important components of social cognition are basic emotion recognition and ‘theory of mind’ (ToM), the ability to understand another person’s mental state, including their thoughts, feelings and intentions. Deficits in both emotion recognition and ToM have been identified in HD [6]. Emotion recognition deficits arise very early in HD and the ability to recognise negative emotions, such as disgust and fear, has been established as a sensitive measure of disease progression [7]. Additionally, a selective ToM deficit in HD has been reported, which affects social inference abilities [8]. However, studies of social cognition in HD to date have failed to identify relationships between social cognitive deficits and functional or behavioural outcomes [9]. A very recent review conducted meta-regression analyses to determine whether any clinical measures were related to social cognitive abilities in HD [6]. These analyses revealed that greater social cognitive impairments were associated with more severe motor symptoms and longer duration of illness. Such findings would seem to suggest that social cognitive impairments increase as the disease progresses; however, the consequent functional decline in terms of everyday abilities has been largely overlooked. On the other hand, psychosocial difficulties and behavioural problems in HD, but not physical or cognitive factors, were predictive of long-term residential care placement [10]. Furthermore, social cognitive deficits have been found to have devastating consequences on interpersonal functioning, quality of life and carer burden in other brain disorders [11].

One possible reason for the lack of relationship between social cognition measures and functional, mood and behavioural outcomes in HD, is that the social cognition measures used in HD research have generally lacked ecological validity. Social cognition is challenging to test experimentally in an ecologically-valid manner, due to the spontaneous and dynamic nature of everyday social interactions. Moreover, existing tasks likely draw on cognitive and affective abilities differentially, which could explain the heterogeneity of findings [12]. In general, important components to assess include the understanding of verbal, paralinguistic and non-verbal cues, as well as interpretation of the social context, which involves a complex interplay of incoming visual and auditory information with previously-learnt knowledge and emotional reactions [13]. Recently, a measure of social cognition was designed specifically for use in brain injured populations, employing professionally-enacted video vignettes of social situations. This tool, known as The Awareness of Social Inference Test (TASIT), measures both emotion recognition skills and the capacity to understand conversational inferences in situations where the literal verbal exchange may be contradicted by the context [14]. TASIT has been utilised across a number of clinical groups in the last decade, including traumatic brain injury [15], Parkinson’s disease [16] and Multiple Sclerosis [17]. TASIT represents a candidate measure for inclusion in clinical test batteries because is it straight-forward to administer and score, has good psychometric properties, and stimuli are designed to approximate real-world social exchanges [15]. To our knowledge, there is only one recently-published paper describing the use of TASIT in a sample of HD participants. This study revealed that symptomatic, but not premanifest HD participants, were significantly impaired for all of the emotion evaluation and social inference subtests of TASIT, compared with controls [18]. However, this study was conducted in Danish and used either muted videos or Danish translations for TASIT stimuli. Furthermore, the study failed to account for the level of cognitive impairment in HD participants: a limitation to be addressed in future studies in order to clarify the relative contributions of cognitive and affective processes to ToM performance in HD.

The current study sought to use TASIT to assess social cognition in an ecologically-valid context in HD, and relate this to behavioural and communication changes, in order to understand the impact of social cognitive impairments in everyday life. As such, a number of clinical, cognitive, neuropsychiatric and functional measures were administered, and data was obtained from several sources, including family members. Specifically, the primary aim of this paper was to determine the utility of TASIT for investigating social cognitive deficits in cognitively-impaired HD individuals, compared with healthy controls. The second aim was to establish the clinical, cognitive and neuropsychiatric correlates of TASIT performances, including measures of empathy, social communication and behavioural/functional changes. First, we hypothesised that TASIT performances would be significantly poorer for emotional evaluation and social inference subtests in HD participants, compared with controls. Second, it was predicted that poorer TASIT scores would be associated with longer disease duration, more severe motor symptoms, greater cognitive impairment, reduced empathy, poorer conversational skills, increased behavioural disturbances and greater functional decline.

MATERIALS AND METHODS

Participants

The total sample comprised 41 primary participants aged between 42 and 76 years, consisting of 17 individuals with HD and 24 healthy controls. Each participant nominated a ‘close other’ to participate in the study as an informant. The HD and control groups were matched for all demographic variables: age, gender, level of education, employment status, relationship to the informant, informant age, informant gender and the informant’s employment status. Fifty-one percent of the primary sample had completed secondary schooling or higher, and 61% were not currently working. Informants were predominantly partners (61%) and children (27%), female (68%) and employed in a full- or part-time capacity (65%).

Participants underwent detailed screening prior to recruitment and were all free from brain injury, neurological or psychiatric conditions (other than HD). Non-English speakers and those with significant hearing impairment were excluded from the study. HD participants were recruited from a statewide specialist multidisciplinary HD clinic. For inclusion in the study, participants were required to meet criteria for a clinical diagnosis of HD with genetic confirmation. Time since clinical diagnosis ranged from 1 to 15 years. HD participants also underwent a clinical neurological assessment using the Unified Huntington’s Disease Rating Scale (UHDRS) and total motor scores ranged from 11 to 66 [1]. Demographic and clinical information is presented in Table 1.

Informed consent was collected from all participants. Ethical approval was obtained from the Calvary Health Care Bethlehem Human Research Ethics Committee.

Materials

TASIT (shortened version). The Emotion Evaluation and Social Inference (minimal) subtests were used from TASIT to assess comprehension of basic emotion and ToM [see ref: 19]. TASIT is a widely-used, reliable and well-validated test of social cognitive abilities, and the shortened version has comparable psychometric properties [19]. Shortened TASIT was selected to halve the administration time, which is important for participants with neurological disease undergoing cognitive assessment. While not previously administered in English in a HD population, the shortened version of TASIT has previously been used in another English-speaking neurodegenerative population, namely Motor Neurone disease [see ref: 20]. Fourteen video vignettes from the Emotion Evaluation subtest were used, with portrayals of positive (‘happiness’, ‘surprise’ and ‘neutral’) and negative emotions (‘anger’, ‘disgust’, ‘fear’ and ‘sadness’). Participants selected the emotion portrayed from a response card with the emotions listed in random order. For the Social Inference subtest, nine video vignettes of actors making ‘sincere’, ‘sarcastic’ or ‘paradoxically sarcastic’ (i.e., a statement that can only make sense when interpreted as sarcastic) statements were shown. Participants then answered four different types of questions about what a specific actor was ‘doing’, ‘saying’, ‘thinking’ and ‘feeling’. Vignettes were shown on a 15-inch computer screen, with attached loudspeakers. Lower scores on each subscale indicate poorer social cognitive skills.

Hospital Anxiety and Depression Scale (HADS). The HADS was used to assess symptoms of mood disturbance [21]. The HADS is a well-validated and reliable 14-item self-report questionnaire rated on a 4-point Likert scale. Scores of eight or greater on either of the anxiety or depression subscales are suggestive of the possible existence of a mood disorder.

Addenbrooke’s Cognitive Examination – Revised (ACE-R). The ACE-R was used to measure cognitive functioning [22]. It is a reliable and valid cognitive screening tool that has been found to be sensitive to signs of cognitive dysfunction. The ACE-R assesses five domains: memory, visuospatial function, verbal fluency, language and attention/orientation skills. Scores range from 0 to 100, with lower scores indicative of poorer cognitive abilities.

Brixton Spatial Anticipation Test. This measure is an executive function test, with minimal motor and speech demands, that assesses a participant’s ability to detect and follow a rule [23]. The reliability and validity of this measure has been established in healthy individuals and across a number of clinical groups. Scores range from 0 to 55 and reflect errors, such that higher scores indicate worse performances.

Frontal Systems Behavior Scale (FrSBe). The FrSBe is a 46-item scale designed to measure behaviours associated with frontal lobe disturbances [24]. The FrSBe has two parallel forms for self- and family ratings, which yield three subscale scores: apathy, disinhibition and executive dysfunction. T-scores, calculated from normative data, 65 or greater are indicative of ‘clinical abnormality’, while T-scores between 60 and 64 reflect a ‘borderline impairment’. The utility of the FrSBe in HD populations is well-established, and it is a highly reliable and valid tool.

Toronto Empathy Questionnaire (TEQ). The TEQ is a brief self- and informant rated measure of a wide range of empathy-related behaviours, with good reliability and validity [25]. It has 16 items rated on a 5-point Likert scale, with eight negatively scored items, such that lower total scores reflect poorer empathy.

La Trobe Communication Questionnaire (LCQ). The LCQ is a well-validated, reliable measure of perceived communicative abilities via self- and informant report. It was originally developed with a large normative sample [26] and further evaluated in the context of traumatic brain injury [27]. It is a 30-item questionnaire in which respondents rate conversational behaviours on a 4-point Likert scale, with higher scores reflecting greater impairment.

Cambridge Behavioural Inventory – Revised (CBI-R). The CBI-R is a 45-item test with 10 subscales: memory and orientation, everyday skills, self-care, abnormal behaviour, mood, beliefs, eating habits, sleep, stereotypic and motor behaviours, and motivation [28]. Caregivers rate each item on a 5-point Likert scale, with higher scores indicating more frequent problems.

Data analysis

Statistical analyses were conducted using IBM SPSS (version 20). TASIT data was not significantly skewed and thus parametric statistical tests were employed, consistent with previous studies [e.g., refs: 11; 16; 17]. Group differences were primarily investigated with independent measures t-tests. Pearson’s coefficients were used for correlational analyses. We focused on total scores for each measure to limit the number of comparisons. The nominal threshold for significance was α= 0.05.

RESULTS

As shown in Fig. 1, HD participants were significantly impaired on all subtests of TASIT compared with controls, except for evaluating positive emotions (p = 0.07; all other p < 0.05). Effect sizes (Cohen’s d) ranged from 0.79 to 1.81.

Cognitive and neuropsychiatric data obtained from primary participants and their informants are presented in Table 1. Neither HD participants nor their informants exhibited clinically significant signs of depression or anxiety on the HADS. Thus, significant mood or anxiety disorder was not deemed a confounding factor to either HD participant performances or informant ratings. Data in Table 1 shows significant impairments across a number of measures in HD participants, compared with controls. Informant FrSBe ratings indicated that HD individuals were showing clinical abnormalities in their behaviour, with T-scores ≥65 for apathy and executive dysfunction. Table 1 also highlights the difference between self- and informant ratings for the FrSBe, TEQ and LCQ, such that HD participants show reduced self-awareness of their apparent difficulties. Therefore, subsequent correlational analyses focused on informant ratings of behaviour, empathy and social communication skills.

Pearson’s correlations were used to explore associations between TASIT scores and the cognitive and neuropsychiatric variables (see Table 2). Importantly, ACE-R scores were only significantly associated with the evaluation of negative emotions, reflecting the fact that TASIT performance was not strongly dependent on core cognitive abilities. Pearson’s correlations were also used to investigate associations between TASIT scores and clinical variables, however TASIT subscales were not significantly correlated with either disease duration or UHDRS total motor scores.

DISCUSSION

This study sought to investigate the social cognitive abilities of HD individuals with significant cognitive impairment, including their emotion evaluation skills and understanding of social inference, such as sarcasm, via use of a novel task. The focus of this paper was to characterise HD-related deficits in social processing in an ecologically-valid context, with regards to their cognitive and neuropsychiatric underpinnings, and their everyday functional implications. Our study revealed that HD individuals showed significantly reduced negative emotion evaluation skills, compared with healthy controls. HD individuals also exhibited significantly poorer social inference abilities, in terms of understanding and interpreting sincere statements, sarcasm and paradoxical sarcasm. These findings were broadly consistent with our primary hypothesis. Secondly, correlational analyses revealed that overall cognitive abilities were significantly associated with negative emotion evaluation. In addition, executive functioning was negatively correlated with social inference skills. Lastly, behavioural problems were negatively correlated with positive emotion evaluation abilities, but no other clinical or functional correlates emerged. Findings from correlational analyses partially supported our hypotheses. In sum, our study revealed significant impairments in social cognition in HD, but these were not robustly related to changes in behaviour and communication.

Our finding of impaired ability to recognise negative emotions in HD, such as anger, fear and disgust, is well-supported by prior research [e.g., ref: 7]. Moreover, previous studies have demonstrated that such deficits remain after minimising the mental and verbal demands of the tasks, which was interpreted to be indicative of neuropathological causes in HD participants [29]. Previous findings regarding the recognition of positive emotions in HD participants are mixed [see ref: 30]. Our marginally significant finding is difficult to interpret but is broadly reflective of the only previously published paper using TASIT in HD, which found that symptomatic HD participants were impaired in evaluating both positive and negative emotions relative to controls [18]. However, our findings would also align with the recent meta-analysis by Henley et al. [31], which concluded that deficits in positive emotion recognition are not consistently found in symptomatic HD. Compared with the Danish study, which used muted videos, task difficulty may have been lessened for HD participants in our study by providing the verbal and paralinguistic cues [18]. Another explanation is that discrepancies between studies are mediated by differences in disease severity among HD participants, as negative emotions may be affected very early in disease progression, with emotion recognition deficits becoming more widespread in manifest disease stages [6]. Indeed, the consistent finding that emerges, regardless of our marginally significant result, is that the recognition of negative emotions is more severely affected than positive emotions in HD [31].

Corroborating Larsen et al.’s [18] findings, we showed impairments for HD individuals on all aspects of the social inference subtest. Larsen et al. suggested that HD individuals might have a specific difficulty with misconstruing ambiguous social and emotional cues, as opposed to understanding sarcasm per se. Indeed, use of TASIT with other clinical groups, including traumatic brain injury and schizophrenia, has indicated that patients performed similarly to healthy controls for the sincere statements [14]. That our sample showed inference deficits for all types of vignettes might suggest a more generalised social processing deficit with regards to the complex integration of verbal, paralinguistic, non-verbal and contextual cues simultaneously [6]. In line with this notion, Snowden et al. [32] reported that HD participants did attempt to make social inferences on a ToM task, but these were typically inappropriate and misconstrued the contents of the cartoon story. McDonald et al. [33] have discussed the theory that social inference impairments may be explained by the loss of implicit social cognition in acquired neurological conditions, which would fit with our data. Our findings also serve to highlight the ecological validity of TASIT for capturing social processing problems, given that HD participants perform similarly to healthy individuals in the ‘control’ conditions of other ToM tasks [12]. In HD participants, it is possible that TASIT might draw on social functions not targeted by the questionnaire measures, or not recognised by patients and caregivers.

This generalised social processing deficit in HD, affecting the performance of all types of social inference tasks, appeared to occur in addition to cognitive dysfunction and disease severity, based on the correlational findings. Indeed, while some previous studies have found associations between executive function and ToM performance, these correlations are relatively weak and can be dissociated from ToM processes [14]. ACE-R scores explained 36% of the variance in negative emotion evaluation abilities and Brixton scores explained up to 41% of social inference abilities in our HD sample. These correlations suggest that the interpretation of different emotions and social exchanges is reliant on cognitive processes to an extent, but also draw on additional functions (e.g., ToM). Our findings might reflect a strength of TASIT over other ToM tasks, as it poses several questions to participants to assess their reasoning, rather than relying on a single response. An alternative explanation for the correlation between executive function and TASIT scores is that HD individuals have difficulty inhibiting a more automatic, literal response on the sarcastic and paradoxical sarcastic vignettes [4]. This interpretation is supported by the body of work outlining inhibitory deficits in HD [34], which may in fact be mediated by similar underlying circuitry as these social inference impairments. Moreover, Allain et al. [35] suggested that the Brixton test specifically draws on inductive reasoning abilities, which could explain its association with social inferences subtests. The social processing deficit suggested by these results, and supported by other work [18; 32], could be investigated in future studies using eye-tracking technology to determine whether HD individuals show abnormal patterns of processing the video stimuli.

The only significant correlation we found between TASIT scores and behavioural ratings was for positive emotion evaluation and CBI-R scores. This suggests that misidentifications of neutral, happy and surprised facial expressions were associated with increased behavioural problems. It seems likely that this relationship is reflective of the severity of HD, in that individuals that generally misperceive all emotions exhibit increased neuropsychiatric signs [31]. The fact that TASIT scores were not significantly related to other behavioural/functional variables might indicate that the questionnaire measures tap into separate aspects of social interactions than those measured by TASIT. Further, TASIT may be able to capture subtle changes in functional capabilities that neither participants nor their informants appreciate, but nonetheless have an impact on everyday interactions. Alternatively, social cognitive impairments may not have an impact on functional outcomes in individuals with well-established symptomatic HD, possibly because their general cognitive and other deficits are the main driving forces of functional disability by this stage. Overall, our correlational results seem to suggest that TASIT performance in HD draws more on the cognitive ToM abilities than affective processes. Previous research in other clinical populations, such as schizophrenia, has indicated that TASIT performances are related to everyday conversational and functional abilities [36, 37]. We chose to focus on informant reports and total scores for this study to limit the number of comparisons, however TASIT scores might be more specifically associated with particular aspects of behaviour, such as the ‘partner sensitivity’ items on the LCQ. Moreover, we did not investigate each emotion individually as participants were only presented with two vignettes for each, thus further investigation of these deficits using the full version of TASIT would be valuable. Given the non-significance of the correlations with many of the functional and behavioural measures used in this study, further investigation is necessary to ascertain the everyday consequences of ToM deficits in HD. Our generally large statistical effect sizes suggest that these social processing deficits are likely to have clinical significance. The lack of relationship between the clinical indicators of disease severity and TASIT scores could be explained by the nature of our HD sample, which comprised HD participants with well-established disease. If established symptomatic disease is indeed associated with a more generalised social cognitive deficit, there may in fact be a range restriction effect. That is, once a generalised impairment is present, disease severity may be less of a factor. Therefore, it is possible that a significant relationship may emerge if both premanifest participants and participants with early symptomatic HD were included in the study.

Neuroanatomical theories of pathology in HD would be consistent with the deficits observed in the present study, mediated by disturbances to frontostriatal circuitry, together with limbic and other basal ganglia pathways [38]. However, this notion cannot be directly substantiated without corresponding neuroimaging data. As such, multimodal neuroimaging investigations will be important in future to delineate the particular neural networks involved in emotion evaluation and social inference abilities in HD.

A study limitation that warrants recognition is the sample size and lack of premanifest and early symptomatic HD participants. Future studies with larger numbers of participants might have increased power to detect underlying associations between TASIT scores and clinical, functional and behavioural measures. Moreover, investigation of the decline in social processing abilities across different disease stages via longitudinal studies would be beneficial. A better understanding of such decline could potentially advance the clinical use of evidence-based interventions with timely, tailored cognitive and behavioural interventions to reduce problematic behaviours stemming from social cognitive deficits. In addition, the shortened version of TASIT we used has not been specifically validated for use in English-speaking HD populations, a limitation that future studies could address. We chose to administer this version as the original TASIT is too long for HD participants, there was no validated shortened version when we conducted our study, and it had been successfully utilised in participants with Motor Neurone Disease previously [20]. However, it is possible that factors, other than ToM deficits, could have contributed to the performances of HD individuals on this task, such as oculomotor impairments. Our use of the shortened TASIT may explain the lack of neuropsychiatric and functional correlates because validation studies suggest that the ‘enriched’ social inference stimuli (the subtest we did not include) are more related to behaviours such as egocentricism and social manners [13]. Lastly, numerous complexities within the carer-care recipient relationships may have contributed to the informant’s perception of the HD individual’s behaviour, which cannot strictly be compared with the close relationship between two people not affected by a neurological disease (i.e., healthy controls and their nominated informants). Indeed, the type of relationship between participants and informants (i.e., a partner compared with a child) might mediate the expectations of behaviours, such as empathy, a factor we did not control for.

In conclusion, manifest HD is associated with significant impairments in ToM (i.e., making social inferences) and emotion recognition (particularly for negative emotions), as assessed using an ecologically-valid task. Whilst these impairments were correlated with cognitive abilities to an extent, including executive functioning, they were not generally related to clinical severity, neuropsychiatric or socially-relevant functional measures (i.e., empathy, conversational abilities). These results provide important new insights into social cognitive and ToM deficits in HD, which are known to have a functional impact in everyday life. However, further research is needed to fully characterise the nature of such deficits, including their cognitive and affective underpinnings, and contributions to everyday behavioural and functional difficulties. Based on our results, we suggest firstly, that clinical assessment should routinely involve investigation of social cognitive abilities, using an ecologically-valid task, such as TASIT, with dynamic, socially-relevant stimuli. This is necessary due to the frequent and pervasive nature of such deficits, and the failure of conventional neuropsychological tests to fully capture them. Secondly, these findings highlight potential areas for clinical interventions that may target underlying causes for interpersonal and behavioural problems in HD individuals, or bypass areas of difficulty to assist with everyday social functioning.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

Footnotes

ACKNOWLEDGMENTS

The authors would like to thank all the participants who made this study possible. The authors would also like to acknowledge the Bethlehem Griffiths Research Foundation for providing the funding support for this research. Thank you to Roxanne Maule, Sally Brinkmann, Michelle Schilders, and Renee Lichter for their contributions to data collection and management during this project.

References

Huntington Study GrouUnified Huntington’s disease rating scale: Reliability and consistency. Mov Disorders. 1996;112:136–42.

Stout

, Paulsen

, Queller

, Solomon

, Whitlock

, Campbell

, et al. Neurocognitive signs in prodromal Huntington’s disease. Neuropsychology. 2011;251:1–14.

Georgiou-Karistianis

, Gray

, Domínguez

DJF

, Dymowski

, Bohanna

, Johnston

, et al. Automated differentiation of pre-diagnosis Huntington’s disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: The IMAGE-HD study. Neurobiol Dis. 2013;51:82–92.

Kipps

, Nestor

, Acosta-Cabronero

, Arnold

, Hodges

. Understanding social dysfunction in the behavioural variant of frontotemporal dementia: The role of emotion and sarcasm processing. Brain. 2009;132:592–603.

Shamay-Tsoory

, Tomer

, Aharon-Peretz

. The neuroanatomical basis of understanding sarcasm and its relationship to social cognition. Neuropsychology. 2005;193:288–300.

Bora

, Velakoulis

, Walterfang

. Social cognition in Huntington’s disease: A meta-analysis. Behav Brain Res. 2016;297:131–40.

Tabrizi

, Langbehn

, Leavitt

, Roos

, Durr

, Craufurd

, et al. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data. Lancet Neurol. 2009;8:791–801.

Brüne

, Blank

, Witthaus

, Saft

. “Theory of mind” is impaired in Huntington’s disease. Mov Disorders. 2011;264:671–8.

Eddy

, Mahalingappa

, Rickards

. Is Huntington’s disease associated with deficits in theory of mind?Acta Neurol Scand. 2012;126:376–83.

10.

Fisher

, Andrews

, Churchyard

, Mathers

. Home or residential care? The role of behavioural and psychosocial factors in determining discharge outcomes for inpatients with Huntington’s disease. J Huntingtons Dis. 2012;1:187–93.

11.

McDonald

, Gowland

, Randall

, Fisher

, Osborne-Crowley

, Honan

. Cognitive factors underpinning poor expressive communication skills after traumatic brain injury: Theory of mind or executive function?Neuropsychology. 2014;285:801–11.

12.

Adjeroud

, Besnard

, El Massioui

, Verny

, Prudean

, Scherer

, et al. Theory of mind and empathy in preclinical and clinical Huntington’s disease. Soc Cogn Affect Neurosci. 2016;111:89–99.

13.

McDonald

. New frontiers in neuropsychological assessment: Assessing social perception using a standardised instrument, The Awareness of Social Inference Test. Aust Psychol. 2012;47:39–48.

14.

McDonald

, Flanagan

, Rollins

, Kinch

. TASIT: A new clinical tool for assessing social perception after traumatic brain injury. J Head Trauma Rehabil. 2003;183:219–38.

15.

McDonald

, Bornhofen

, Shum

, Long

, Saunders

, Neulinger

. Reliability and validity of The Awareness of Social Inference Test (TASIT): A clinical test of social perception. Disabil Rehabil. 2006;2824:1529–42.

16.

Pell

, Monetta

, Rothermich

, Kotz

, Cheang

, McDonald

. Social perception in adults with Parkinson’s disease. Neuropsychology. 2014;286:905–16.

17.

Genova

, Cagna

, Chiaravalloti

, DeLuca

, Lengenfelder

. Dynamic assessment of social cognition in individuals with multiple sclerosis: A pilot study. J Int Neuropsychol Soc. 2016;22:83–8.

18.

Larsen

, Vinther-Jensen

, Gade

, Nielsen

, Vogel

. Do I misconstrue? Sarcasm detection, emotion recognition, and theory of mind in Huntington disease. Neuropsychology. 2015;29(in press):1–9.

19.

Westerhof-Evers

, Visser-Keizer

, McDonald

, Spikman

. Performance of healthy subjects on an ecologically valid test for social cognition: The short, Dutch version of The Awareness of Social Inference Test (TASIT). J Clin Exp Neuropsychol. 2014;3610:1031–41.

20.

Staios

, Fisher

, Lindell

, Ong

, Howe

, Reardon

. Exploring sarcasm detection in amyotrophic lateral sclerosis using ecologically valid measures. Front Hum Neurosci. 2013;7178:1–9.

21.

Zigmond

, Snaith

. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70.

22.

Mioshi

, Dawson

, Mitchell

, Arnold

, Hodges

. The Addenbrooke’s Cognitive Examinaton Revised (ACE-R): A brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry. 2006;21:1078–85.

23.

Van Den Berg

, Nys

, Brands

, Ruis

, Van Zandvoort

, Kessels

. The Brixton Spatial Anticipation Test as a test for executive function: Validity in patient groups and norms for older adults. J Int Neuropsychol Soc. 2009;15:695–703.

24.

Malloy

, Grace

. A review of rating scales for measuring behavior change due to frontal systems damage. Cog Behav Neurol. 2005;181:18–27.

25.

Spreng

, McKinnon

, Mar

, Levine

. The Toronto Empathy Questionnaire: Scale development and initial validation of a factor-analytic solution to multiple empathy measures. J Pers Assess. 2009;911:62–71.

26.

Douglas

, O’Flaherty

, Snow

. Measuring perception of communicative ability: The development and evaluation of the La Trobe Communication Questionnaire. Aphasiology. 2000;143:251–68.

27.

Douglas

, Bracy

, Snow

. Measuring perceived communicative ability after traumatic brain injury: Reliability and validity of the La Trobe Communication Questionnaire. J Head Trauma Rehabil. 2007;221:31–8.

28.

Wear

, Wedderburn

, Mioshi

, Williams-Gray

, Mason

, Barker

, et al. The Cambridge Behavioural Inventory revised. Dement Neuropsychol. 2008;22:102–7.

29.

Snowden

, Austin

, Sembi

, Thompson

, Craufurd

, Neary

. Emotion recognition in Huntington’s disease and frontotemporal dementia. Neuropsychologia. 2008;46:2638–49.

30.

Löffler

, Radke

, Morawetz

, Derntl

. Emotional dysfunctions in neurodegenerative diseases. J Comp Neurol. 2016;524:1727–43.

31.

Henley

, Novak

, Frost

, King

, Tabrizi

, Warren

. Emotion recognition in Huntington’s disease: A systematic review. Neurosci Biobehav Rev. 2012;36:237–53.

32.

Snowden

, Gibbons

, Blackshaw

, Doubleday

, Thompson

, Craufurd

, et al. Social cognition in frontotemporal dementia and Huntington’s disease. Neuropsychologia. 2003;41:688–701.

33.

McDonald

, Saad

, James

. Social dysdecorum following severe traumatic brain injury: Loss of implicit social knowledge or loss of control?J Clin Exp Neuropsychol. 2011;336:619–30.

34.

Aron

, Schlaghecken

, Fletcher

, Bullmore

, Eimer

, Barker

, et al. Inhibition of subliminally primed responses is mediated by the caudate and thalamus: Evidence from functional MRI and Huntington’s disease. Brain. 2003;126:713–23.

35.

Allain

, Havet-Thomassin

, Verny

, Gohier

, Lancelot

, Besnard

, et al. Evidence for deficits on different components of theory of mind in Huntington’s disease. Neuropsychology. 2011;256:741–51.

36.

Watts

, Douglas

. Interpreting facial expression and communication competence following severe traumatic brain injury. Aphasiology. 2006;208:707–22.

37.

Mancuso

, Horan

, Kern

, Green

. Social cognition in psychosis: Multidimensional structure, clinical correlates, and relationship with functional outcome. Schizophr Res. 2011;125:143–51.

38.

Wichmann

, DeLong

. Functional and pathophysiological models of the basal ganglia. Curr Opin Neurobiol. 1996;6:751–8.