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Background Language has been shown to be affected in Huntington’s disease (HD) in several experimental tasks, independently of cognitive disabilities and since the earliest stages of the disease. However, studies of spontaneous speech are scarce and provide contradictory results. Aims To systematically profile the earliest spontaneous speech errors in HD and to test whether they extend to referential dysfunction in production, as it has been described in previous experimental work testing comprehension. Methods 28 native HD gene-carriers (9 pre-HD) and 28 matched controls were recorded while telling the Cinderella story using a visual support. Speech samples were transcribed and rated by two independent raters using Computarised Language Analysis (CLAN). Measures were normalised and errors were clustered in five different components. All participants underwent MRI scanning and high resolution T1 images were analysed using voxed-based morphometry (VBM) in order to study brain atrophy. Results Manifest HD patients showed increased errors in all five components: Quantitative, comprising the Mean Length of Utterances, the Number of Words, and Words per Minute; Fluency, capturing disturbances in the flow of speech due to abnormal Pauses and Truncations; Connectivity, related to the combining of clauses; Reference, capturing all variables relating to the referential use of language in discourse such as the use of noun phrases to identify objects and establish topics of the discourse; Concordance, related to deficits in grammatical Agreement. In the case of the preHD group, these differences were observed in Connectivity and Reference measures. Correlations of these measures with the voxels showing VBM differences between patients and controls showed that the Quantitative measure correlated with atrophy in bilateral caudate and putamen. The remaining components showed no significant correlation with the VBM differences. Conclusions Striatal atrophy is associated to spontaneous speech deficits. However, deficits in spontaneous speech in HD are characterised not only by dysfluencies related to motor dysfunction but also by syntactic and referential errors in their discourse. Specific deficits in connecting clauses and reference are detectable even before overt clinical symptomatology.

Background Impulsivity in Huntington’s disease (HD) patients has been understudied despite its clear impact in daily life. Although it is known that there are different types of impulsivity, this trait has been mainly studied through impulsive actions in cued go/no-go tasks that contain an important motor component, while the more purely emotional/choice component of impulsivity in HD remains unknown. Objective To study the neurobiological basis that characterise individual differences in emotional impulsivity in HD. Methods Thirty-one controls and 32 HD patients (11 of which were pre-symptomatic) were scanned using diffusion tensor imaging (DTI) to study the relationship between the structural connectivity of the uncinate fasciculus (UF), the main tract involved in the motivational circuit, and the impulsivity trait (k), evaluated with a delay discounting task. Results No significant difference was observed in k between the two groups. In controls, k correlated with both right and left UF, whereas in HD patients, k correlated only with the left UF. On the other hand, only the right UF was found to be affected in HD patients compared with controls. Conclusion This study reveals that HD patients do not differ from controls in the impulse behaviour associated with delay discounting choices. Moreover, the connectivity pattern observed in HD patients and controls is consistent with previous studies that show that individual differences in microstructure integrity of the left UF are related to impulsivity levels in delay discounting tasks.

Background Although age of onset of Huntington’s disease (HD) is mainly determined by the size of the CAG repeat expansion, other factors may play a role. One potential factor is Cognitive Reserve (CR), as it has been shown in other neurodegenerative disorders and ageing. Objective The objective of this study is to investigate the effect of CR on age of onset in HD and to examine the neural bases underlying the individual differences in executive function that could be due to the effects of CR in HD. Methods Thirty-one HD patients completed a CR questionnaire and were scanned using functional magnetic resonance imaging. We analysed the Resting State Executive Control Network (RS-ECN), a novel approach to study the brain areas underlying executive function. The strength of connectivity with this network was calculated voxel-wise. The difference between the theoeretical and estimated age of onset (26 symptomatic-HD) was calculated for each patient. Results Our results revealed that high levels of CR significantly delayed the appearance of clinical symptoms. Functional connectivity and morphometry analysis showed a brain reorganisation modulated by CR, which changed the connectivity strength in the anterior cingulate cortex, in the left superior parietal cortex (SPC) and slowed the volume loss in the bilateral precuneus and the bilateral caudate. Furthermore, higher strength of connectivity in the left SPC was related to better performance in cognitive flexibility (TMT B-A) and working memory (Backward Digits Span) tasks. Conclusions These findings provide converging evidence that CR might act as a protective mechanism for the progression of the disease, delaying the onset of symptoms and improving the performance in executive functions by modulating the RS-ECN and slowing brain atrophy.