Striatal degeneration impairs language learning: evidence from Huntington's disease

Abstract

Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly correlated with the bicaudate ratio. The overall results support striatal involvement in rule extraction from speech and suggest that language acquisition requires several aspects of memory and executive functions for word and rule learning.

Figure 1

Illustration of the material used in the learning phase. Words (i.e., patemi) and rules (i.e., the structure pa__mi) could be acquired from the same material.

Figure 2

Mean performance (± standard error of the mean) of the healthy control group and the Huntington’s Disease gene carriers (HD) for the word and the rule learning tests. A. Rule and word learning performance of the healthy control group and all the HD patients of the study at different stages of the disease. B. Rule learning performance of the healthy control group, Pre-HD and stage I HD patients when matched for their word learning performance. Pre-HD: Pre-symptomatic gene-carriers of HD; HD₁: HD patients at stage I; HD₂: HD patients at stages II, III and IV.

Figure 3

Proportions of correct responses in the first and second block of the learning tests. Transfer scores are superimposed, calculated as the difference in performance from the first to the second block of languages tested (scores for words and rules together). * p < .021. Bars indicate ± standard error of the mean.