Huntington's disease (HD) is traditionally associated with motor, cognitive, and neuropsychiatric symptoms. Recent observations suggest that disturbances in social cognition may feature prominently in HD, potentially contributing to behavioral challenges.
Objective
This study aims to explore the onset and neural mechanisms underlying social cognition disturbances in HD, which are not yet well understood despite increasing recognition of these symptoms.
Methods
This study compared 20 individuals in the early stages of HD with 20 healthy controls across a range of cognitive tests, in-depth social cognition assessments, and structural MRI evaluations.
Results
The findings revealed alterations in various aspects of social cognition, particularly cognitive and affective Theory of Mind, in the early HD group. Some of these alterations correlated with the neurodegeneration of the striatum (caudate), suggesting that social cognition deficits may serve as early indicators of disease progression.
Conclusions
This research underscores the importance of integrating social cognition evaluations into the clinical assessment of HD and hints at a complex interplay between these deficits and the broader neuropsychological impact of the disease. The results thus advocate for a more holistic approach to understanding and managing HD, considering the potential interdependencies between social cognition and other cognitive functions.
Huntington Study Group. Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord1996; 11: 136–142.
2.
MontoyaAPriceBHMenearM, et al.Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci2006; 31: 21–29.
3.
PaulsenJSLangbehnDRStoutJC, et al.Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry2008; 79: 874–880.
4.
TabriziSJLangbehnDRLeavittBR, et al.Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol2009; 8: 791–801.
5.
CraufurdDSnowdenJ. Neuropsychological and neuropsychiatric aspects of Huntington’s disease. Oxford Monogr Med Genet2002; 45: 62–94.
6.
SnowdenJSGibbonsZCBlackshawA, et al.Social cognition in frontotemporal dementia and Huntington’s disease. Neuropsychologia2003; 41: 688–701.
7.
AllainPHavet-ThomassinVVernyC, et al.Evidence for deficits on different components of theory of mind in Huntington’s disease. Neuropsychology2011; 25: 741–751.
8.
EddyCMParkinsonEGRickardsHE. Changes in mental state and behaviour in Huntington’s disease. Lancet Psychiatry2016; 3: 1079–1086.
BeerJSOchsnerKN. Social cognition: a multi level analysis. Brain Res2006; 1079: 98–105.
11.
StoneVEGerransP. What’s domain-specific about theory of mind?Soc Neurosci2006; 1: 309–319.
12.
BoraEVelakoulisDWalterfangM. Social cognition in Huntington’s disease: a meta-analysis. Behav Brain Res2016; 297: 131–140.
13.
HenleySMDNovakMJUFrostC, et al.Emotion recognition in Huntington’s disease: a systematic review. Neurosci Biobehav Rev2012; 36: 237–253.
14.
RobothamLSauterDABachoud-LéviA-C, et al.The impairment of emotion recognition in Huntington’s disease extends to positive emotions. Cortex2011; 47: 880–884.
15.
LabuschagneIJonesRCallaghanJ, et al.Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington’s disease. Psychiatry Res2013; 207: 118–126.
16.
TracyJLRobinsRW. Putting the self into self-conscious emotions: a theoretical model. Psychol Inq2004; 15: 103–125.
17.
YitzhakNGurevichTInbarN, et al.Recognition of emotion from subtle and non-stereotypical dynamic facial expressions in huntington’s disease. Cortex2020; 126: 343–354.
18.
EddyCMRickardsHE. Moral judgment and decision making in Huntington’s disease. Basal Ganglia2012; 2: 139–142.
19.
DuclosHde La SayetteVBonnetA-L, et al.Social cognition in the frontal variant of Alzheimer’s disease: a case study. J Alzheimers Dis2016; 55: 459–463.
20.
MendezMFShapiraAESJ. An investigation of moral judgement in frontotemporal dementia. Cogn Behav Neurol2005; 18: 193–197.
Baron-CohenSLeslieAMFrithU. Does the autistic child have a “theory of mind” ?Cognition1985; 21: 37–46.
23.
BrothersLRingB. A neuroethological framework for the representation of minds. J Cogn Neurosci1992; 4: 107–118.
24.
BrüneMBlankKWitthausH, et al.Theory of mind’ is impaired in Huntington’s disease. Mov Disord2011; 26: 671–678.
25.
CaillaudMLaisneyMBejaninA, et al.Specific cognitive theory of mind and behavioral dysfunctions in early manifest Huntington disease: a case report. Neurocase2020; 26: 36–41.
26.
LagravineseGAvanzinoLFerrariD, , et al.Theory of mind is impaired in mild to moderate Huntington’s disease independently from global cognitive functioning. Front Psychol2017; 8: 80.
27.
EddyCMSira MahalingappaSRickardsHE. Is Huntington’s disease associated with deficits in theory of mind?Acta Neurol Scand2012; 126: 376–383.
28.
LarsenIUVinther-JensenTGadeA, et al.Do I misconstrue? Sarcasm detection, emotion recognition, and theory of mind in huntington disease. Neuropsychology2016; 30: 181–189.
29.
AdjeroudNBesnardJMassiouiNE, et al.Theory of mind and empathy in preclinical and clinical Huntington’s disease. Soc Cogn Affect Neurosci2016; 11: 89–99.
30.
MauragePLahayeMGrynbergD, et al.Dissociating emotional and cognitive empathy in pre-clinical and clinical Huntington’s disease. Psychiatry Res2016; 237: 103–108.
31.
SaftCLissekSHoffmannR, et al.Mentalizing in preclinical Huntington’s disease: an fMRI study using cartoon picture stories. Brain Imaging Behav2013; 7: 154–162.
32.
EddyCMRickardsHE. Theory of mind can be impaired prior to motor onset in Huntington’s disease. Neuropsychology2015; 29: 792–798.
33.
HenleySMDWildEJHobbsNZ, et al.Defective emotion recognition in early HD is neuropsychologically and anatomically generic. Neuropsychologia2008; 46: 2152–2160.
34.
DoganISaßCMirzazadeS, et al.Neural correlates of impaired emotion processing in manifest Huntington’s disease. Soc Cogn Affect Neurosci2014; 9: 671–680.
35.
NovakMJUSeunarineKKGibbardCR, et al.White matter integrity in premanifest and early Huntington’s disease is related to caudate loss and disease progression. Cortex2014; 52: 98–112.
36.
HarringtonDLLiuDSmithMM, et al.Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease. Brain Behav2014; 4: 29–40.
37.
MasonSLZhangJBegetiF, et al.The role of the amygdala during emotional processing in Huntington’s disease: from pre-manifest to late stage disease. Neuropsychologia2015; 70: 80–89.
38.
ShoulsonIFahnS. Huntington disease: clinical care and evaluation. Neurology1979; 29: 1–3.
39.
CardebatDDoyonBPuelM, et al.Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level. Acta Neurol Belg1990; 90: 207–217.
40.
ReitanRM. Validity of the Trail Making Test as an indicator. Percept Mot Skills1958; 8: 271–276.
41.
StroopJR. Studies of interference in serial verbal reactions. J Exp Psychol1935; 18: 643–662.
42.
SmithA. Symbol Digit Modalities Test. Los Angeles: Western Psychological Services, 1982.
43.
BenedictRHBSchretlenDGroningerL, et al.Hopkins verbal learning test – revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychol1998; 12: 43–55.
44.
MattisS. Mental status examination for organic mental syndrome in the elderly patient. In: BellakLKarasuTB (eds) Geriatric psychiatry. New York: Grune & Stratton, 1976, pp.77–121.
45.
van der SchalkJHawkSTFischerAH, et al.Moving faces, looking places: validation of the Amsterdam Dynamic Facial Expression Set (ADFES). Emotion2011; 11: 907–920.
46.
BertouxMDuclosHCaillaudM, et al.When affect overlaps with concept: emotion recognition in semantic variant of primary progressive aphasia. Brain2020; 143: 3850–3864.
47.
CaillaudMBejaninALaisneyM, et al.Influence of emotional complexity on the neural substrates of affective theory of mind. Hum Brain Mapp2020; 41: 139–149.
48.
DesgrangesBLaisneyMBonL, et al.TOM-15 : une épreuve de fausses croyances pour évaluer la théorie de l’esprit cognitive. Rev Neuropsychol2012; 4: 216–220.
49.
WillingerUSchmoegerMMuellerC, et al.Theory of mind & cognitive flexibility. Eur Psychiatry2011; 26: 439–439.
50.
SaftCLissekSHoffmannR, et al.Mentalizing in preclinical Huntington’s disease: an fMRI study using cartoon picture stories. Brain Imaging Behav2013; 7: 154–162.
51.
AdjeroudNBesnardJEl MassiouiN, et al.Theory of mind and empathy in preclinical and clinical Huntington’s disease. Soc Cogn Affect Neurosci2016; 11: 89–99.
52.
MauragePLahayeMGrynbergD, et al.Dissociating emotional and cognitive empathy in pre-clinical and clinical Huntington’s disease. Psychiatry Res2016; 237: 103–108.
53.
PaulsenJSSalmonDPMonschAU, et al.Discrimination of cortical from subcortical dementias on the basis of memory and problem-solving tests. J Clin Psychol1995; 51: 48–58.
54.
KinnunenKMSchwarzAJTurnerEC, et al.Volumetric MRI-based biomarkers in Huntington’s disease: an evidentiary review. Front Neurol2021; 12: 712555.
55.
CraufurdDSnowdenJ. Neuropsychological and neuropsychiatric aspects of Huntington’s disease. Oxford Monogr Med Genet2002; 45: 62–94.
56.
MatzOCSpocterM. The effect of Huntington’s disease on the basal nuclei: a review. Cureus2022; 14: e24473.
57.
PeinemannASchullerSPohlC, et al.Executive dysfunction in early stages of Huntington’s disease is associated with striatal and insular atrophy: a neuropsychological and voxel-based morphometric study. J Neurol Sci2005; 239: 11–19.
58.
Abu-AkelAShamay-TsooryS. Neuroanatomical and neurochemical bases of theory of mind. Neuropsychologia2011; 49: 2971–2984.
59.
VotinovMMyznikovAZheltyakovaM, et al.The interaction between caudate nucleus and regions within the theory of mind network as a neural basis for social intelligence. Front Neural Circuits2021; 15: 727960.
60.
KippsCMDugginsAJMcCuskerEA, et al.Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington’s disease. J Cogn Neurosci2007; 19: 1206–1217.
61.
SturmVEAscherEAMillerBL, et al.Diminished self-conscious emotional responding in frontotemporal lobar degeneration patients. Emotion2008; 8: 861.
62.
KippsCMDugginsAJMcCuskerEA, et al.Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington’s disease. J Cogn Neurosci2007; 19: 1206–1217.
63.
SturmVEAscherEAMillerBL, et al.Diminished self-conscious emotional responding in frontotemporal lobar degeneration patients. Emotion2008; 8: 861.
64.
Corradi-Dell’AcquaCRonchiRThomassonM, et al.Deficits in cognitive and affective theory of mind relate to dissociated lesion patterns in prefrontal and insular cortex. Cortex2020; 128: 218–233.
65.
SchurzMRaduaJTholenMG, et al.Toward a hierarchical model of social cognition: a neuroimaging meta-analysis and integrative review of empathy and theory of mind. Psychol Bull2021; 147: 293–327.
66.
PaulsenJSMagnottaVAMikosAE, et al.Brain structure in preclinical Huntington’s disease. Biol Psychiatry2006; 59: 57–63.
67.
RosasHDSalatDHLeeSY, et al.Cerebral cortex and the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain2008; 131: 1057–1068.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
