Cognitive reserve involves decision making and is associated with left parietal and hippocampal hypertrophy in neurodegeneration.

Cognitive reserve is the ability to actively cope with brain deterioration and delay cognitive decline in neurodegenerative diseases. It operates by optimizing performance through differential recruitment of brain networks or alternative cognitive strategies. We investigated cognitive reserve using Huntington's disease (HD) as a genetic model of neurodegeneration to compare premanifest HD, manifest HD, and controls. Contrary to manifest HD, premanifest HD behave as controls despite neurodegeneration. By decomposing the cognitive processes underlying decision making, drift diffusion models revealed a response profile that differs progressively from controls to premanifest and manifest HD. Here, we show that cognitive reserve in premanifest HD is supported by an increased rate of evidence accumulation compensating for the abnormal increase in the amount of evidence needed to make a decision. This higher rate is associated with left superior parietal and hippocampal hypertrophy, and exhibits a bell shape over the course of disease progression, characteristic of compensation.

Language disorders in patients with striatal lesions: Deciphering the role of the striatum in language performance.

The classical neural model of language refers to a cortical network involving frontal, parietal and temporal regions. However, patients with subcortical lesions of the striatum have language difficulties. We investigated whether the striatum is directly involved in language or whether its role in decision-making has an indirect effect on language performance, by testing carriers of Huntington's disease (HD) mutations and controls. HD is a genetic neurodegenerative disease primarily affecting the striatum and causing language disorders. We asked carriers of the HD mutation in the premanifest (before clinical diagnosis) and early disease stages, and controls to perform two discrimination tasks, one involving linguistic and the other non-linguistic stimuli. We used the hierarchical drift diffusion model (HDDM) to analyze the participants' responses and to assess the decision and non-decision parameters separately. We hypothesized that any language deficits related to decision-making impairments would be reflected in the decision parameters of linguistic and non-linguistic tasks. We also assessed the relative contributions of both HDDM decision and non-decision parameters to the participants' behavioral data (response time and discriminability). Finally, we investigated whether the decision and non-decision parameters of the HDDM were correlated with brain atrophy. The HDDM analysis showed that patients with early HD have impaired decision parameters relative to controls, regardless of the task. In both tasks, decision parameters better explained the variance of response time and discriminability performance than non-decision parameters. In the linguistic task, decision parameters were positively correlated with gray matter volume in the ventral striatum and putamen, whereas non-decision parameters were not. Language impairment in patients with striatal atrophy is better explained by a deficit of decision-making than by a deficit of core linguistic processing. These results suggest that the striatum is involved in language through the modulation of decision-making, presumably by regulating the process of choice between linguistic alternatives.

Structural priming in sentence comprehension: A single prime is enough.

Experiencing a syntactic structure affects how we process subsequent instances of that structure. This phenomenon, called structural priming, is observed both in language production and in language comprehension. However, while abstract syntactic structures can be primed independent of lexical overlap in sentence production, evidence for structural priming in comprehension is more elusive. In addition, when structural priming in comprehension is found, it can often be accounted for in terms of participants' explicit expectations. Participants may use the structural repetition over several sentences and build expectations, which create a priming effect. Here, we use a new experimental paradigm to investigate structural priming in sentence comprehension independent of lexical overlap and of participants' expectations. We use an outcome dependent variable instead of commonly used online measures, which allows us to more directly compare these effects with those found in sentence production studies. We test priming effects in syntactically homogeneous and heterogeneous conditions on a sentence-picture matching task that forces participants to fully parse the sentences. We observe that, while participants learn the structural regularity in the homogeneous condition, structural priming is also found in the heterogeneous condition, in which participants do not expect any particular structure. In fact, we find that a single prime is enough to trigger priming. Our results indicate that-like in sentence production-structural priming can be observed in sentence comprehension without lexical repetition and independent of participants' expectation.

The role of the striatum in linguistic selection: Evidence from Huntington's disease and computational modeling.

Though accumulating evidence indicates that the striatum is recruited during language processing, the specific function of this subcortical structure in language remains to be elucidated. To answer this question, we used Huntington's disease as a model of striatal lesion. We investigated the morphological deficit of 30 early Huntington's disease patients with a novel linguistic task that can be modeled within an explicit theory of linguistic computation. Behavioral results reflected an impairment in HD patients on the linguistic task. Computational model-based analysis compared the behavioral data to simulated data from two distinct lesion models, a selection deficit model and a grammatical deficit model. This analysis revealed that the impairment derives from an increased randomness in the process of selecting between grammatical alternatives, rather than from a disruption of grammatical knowledge per se. Voxel-based morphometry permitted to correlate this impairment to dorsal striatal degeneration. We thus show that the striatum holds a role in the selection of linguistic alternatives, just as in the selection of motor and cognitive programs.

Cortical thickness, stance control, and arithmetic skill: An exploratory study in premanifest Huntington disease.

BACKGROUND: Huntington disease (HD) is an inherited neurodegenerative disorder most commonly manifesting in adulthood. Identification of biomarkers tracking neurodegeneration before the onset of motor symptoms is important for future interventional studies. Our study aimed to contribute in the phenotypic characterization of the premanifest HD phase. METHODS: 28 premanifest subjects (preHD), 25 age-matched controls, and 12 manifest HD patients were enrolled for the study. The participants underwent a multimodal protocol including cognitive evaluations, arithmetic ability test, posturography, composite cerebellar functional test (CCFS), and brain 3T-MRI. PreHD were divided at the group median for predicted years to expected onset into "far-from-onset" (>15 years, PreHD-far), and "close-to-onset" (≤15 years, preHD-close). Basal ganglia volumes and cortical thickness were computed using FreeSurfer. RESULTS: PreHD-close showed significantly lower scores than controls in Symbol Digit Modalities Test (p = 0.017), Arithmetic subtraction task (p = 0.04), and MMSE (p < 0.006). At posturography, preHD-close showed increased sway velocity (<0.04) and distance (p < 0.02) compared to controls. PreHD-close had reduced striatum and globus pallidus volumes and left occipital cortical thinning compared to controls. Compared to PreHD far-from-onset, PreHD-close showed bilateral cortical thinning in occipital and parahippocampal regions, inversely correlating with burden score and prognostic index for HD. CCFS only differed between controls and manifest HD. PreHD far-from-onset did not show significant differences in comparison with controls. CONCLUSIONS: We confirmed that quantitative brain MRI represents a valid biomarker of neurodegeneration in preHD. Posturography and Arithmentic tests seem promising tools for detecting early changes in premanifest HD, but need to be further confirmed in large cohorts.

Complex linguistic rules modulate early auditory brain responses.

During speech perception, listeners compensate for phonological rules of their language. For instance, English place assimilation causes green boat to be typically pronounced as greem boat; English listeners, however, perceptually compensate for this rule and retrieve the intended sound (n). Previous research using EEG has focused on rules with clear phonetic underpinnings, showing that perceptual compensation occurs at an early stage of speech perception. We tested whether this early mechanism also accounts for the compensation for more complex rules. We examined compensation for French voicing assimilation, a rule with abstract phonological restrictions on the contexts in which it applies. Our results reveal that perceptual compensation for this rule by French listeners modulates an early ERP component. This is evidence that early stages of speech sound categorization are sensitive to complex phonological rules of the native language.

The role of the striatum in sentence processing: disentangling syntax from working memory in Huntington's disease.

The role of sub-cortical structures in language processing remains controversial. In particular, it is unclear whether the striatum subserves language-specific processes such as syntax or whether it solely affects language performance via its significant role in executive functioning and/or working memory. Here, in order to address this issue, we attempted to equalize working memory constraints while varying syntactic complexity, to study sentence comprehension in 15 patients with striatal damage, namely Huntington's disease at early stage, and in 15 healthy controls. More particularly, we manipulated the syntactic relation between a name and a pronoun while holding the distance between them constant. We exploited a formal principle of syntactic theory called Principle C. This principle states that whereas in a sentence such as "Paul smiled when he entered" Paul and he can be a single person, this interpretation is blocked in sentences such as "He smiled when Paul entered". In a second experiment we varied working memory load using noun-adjective gender agreement in center-embedded and right-branching relatives (e.g., "the girl who watches the dog is green" vs. "the girl watches the dog which is green"). The results show that HD patients correctly establish name-pronoun co-reference but they fail to block it when Principle C should apply. Furthermore, they have good performance with both center-embedded and right-branching relatives, suggesting that their difficulties in sentence comprehension do not arise from memory load impairment during sentence processing. Taken together, our findings indicate that the striatum holds a genuine role in syntactic processing, which cannot be reduced to its involvement in working memory. However, it only impacts on particular aspects of syntax that may relate to complex computations whereas other operations appear to be preserved. Hypotheses about the role of the striatum in syntactic processing are discussed.