Huntington's disease patients display progressive deficits in hippocampal-dependent cognition during a task of spatial memory.

BACKGROUND: Cognitive disturbances occur early in Huntington's disease (HD) and place a significant burden on the lives of patients and family members. Whilst these impairments are typically attributed to deterioration of the frontal-striatal pathways, accumulating evidence suggests that hippocampal dysfunction may also contribute to such impairments. Here, we employ a novel spatial memory task that has previously been shown to elicit impairments in individuals with focal hippocampal lesions, as a means to further investigate the role of hippocampal dysfunction in HD. METHOD: Sixty-four individuals participated in the study, including 32 healthy controls, 11 patients with diagnosed HD and 16 premanifest HD gene carriers. We also included an additional control group of 5 individuals with focal unilateral basal ganglia lesions. Participants undertook a task that measured perception and short-term spatial memory using computer-generated visual scenes. RESULTS: HD patients experienced significant impairments in spatial perception and memory, which strongly correlated with disease burden score (DBS). Premanifest gene carriers performed at a similar level to healthy controls throughout all aspects of the task indicating that the effects seen in the HD patients represent a deterioration in function. Interestingly, basal ganglia lesion patients were not impaired in any aspects of the task. CONCLUSION: There is evidence of significant deficits in hippocampal-dependent spatial cognition in HD that cannot be explained as a function of degeneration to the basal ganglia. The impairments were greatest in individuals with higher DBSs, suggesting that deficits relate to the disease process in HD

Cognitive Diversity in a Healthy Aging Cohort: Cross-Domain Cognition in the Cam-CAN Project.

Objective: Studies of "healthy" cognitive aging often focus on a limited set of measures that decline with age. The current study argues that defining and supporting healthy cognition requires understanding diverse cognitive performance across the lifespan. Method: Data from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) cohort was examined across a range of cognitive domains. Performance was related to lifestyle including education, social engagement, and enrichment activities. Results: Results indicate variable relationships between cognition and age (positive, negative, or no relationship). Principal components analysis indicated maintained cognitive diversity across the adult lifespan, and that cognition-lifestyle relationships differed by age and domain. Discussion: Our findings support a view of normal cognitive aging as a lifelong developmental process with diverse relationships between cognition, lifestyle, and age. This reinforces the need for large-scale studies of cognitive aging to include a wider range of both ages and cognitive tasks.The Cambridge Centre for Aging and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1)

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss

Updating ambiguous word meanings: a role for the language-selective fronto-temporal network

Semantically ambiguous words (e.g. "bark") challenge word meaning access. An effective comprehension system can use immediate contextual cues and adapt in response to recent experience. We explored the contributions of the domain-specific Language Network and the domain-general Multiple Demand Networks by analysing behavioural data from volunteers with lesions to these two networks. Results from a sentence coherence judgement task show that word meaning access was more challenging for sentences containing ambiguous words (slower response times) but damage location and extent did not affect comprehension accuracy. Results from a subsequent word association task showed an increase in preference for lower frequency word meanings following recent experience with these words (Word Meaning Priming Effect). The size of this effect was reduced when there was greater damage to the Language Network, but not the MD Network and not overall damage, and was not driven by poorer comprehension.</jats:p

Causal contributions of the domain-general (Multiple Demand) and the language-selective brain networks to perceptual and semantic challenges in speech comprehension

Lesion-behaviour correlational study

Updating ambiguous word meanings: a role for the language-selective fronto-temporal network

Semantically ambiguous words (e.g. "bark") challenge word meaning access. An effective comprehension system can use immediate contextual cues and adapt in response to recent experience. We explored the contributions of the domain-specific Language Network and the domain-general Multiple Demand Networks by analysing behavioural data from volunteers with lesions to these two networks. Results from a sentence coherence judgement task show that word meaning access was more challenging for sentences containing ambiguous words (slower response times) but damage location and extent did not affect comprehension accuracy. Results from a subsequent word association task showed an increase in preference for lower frequency word meanings following recent experience with these words (Word Meaning Priming Effect). The size of this effect was reduced when there was greater damage to the Language Network, but not the MD Network and not overall damage, and was not driven by poorer comprehension.</jats:p

Causal contributions of the domain-general (Multiple Demand) and the language-selective brain networks to perceptual and semantic challenges in speech comprehension

1.AbstractListening to spoken language engages domain-general Multiple Demand (MD, fronto-parietal) regions of the human brain, in addition to domain-selective (fronto-temporal) language regions, particularly when comprehension is challenging. However, there is limited evidence that the MD network makes a functional contribution to core aspects of comprehension. In a behavioural study of volunteers (n=19) with chronic brain lesions, but without aphasia, we assessed the causal role of these networks in perceiving, comprehending and adapting to challenging spoken sentences. A first task measured word report for acoustically degraded (noise-vocoded) sentences before and after training. Participants with greater damage to MD but not language regions required more vocoder channels to achieve 50% word report indicating impaired perception. Perception improved following training, reflecting adaptation to acoustic degradation, but perceptual learning was unrelated to lesion location or extent. A second task used sentence coherence judgements to measure the speed and accuracy of comprehension of spoken sentences using lower-frequency meanings of semantically ambiguous words. Comprehension accuracy was high and unaffected by lesion location or extent. The availability of the lower-frequency meaning, as measured in a subsequent word association task, increased following comprehension (word-meaning priming). Word-meaning priming was reduced for participants with greater damage to language but not MD regions. We conclude that language and MD networks make dissociable contributions to challenging speech comprehension: using recent experience to update word meaning preferences depends on language specialised regions, whereas the domain-general MD network plays a causal role in reporting words from degraded speech.</jats:p