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General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

ABSTRACT: Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components : gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 41 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|β| range = 0.15 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.

SUBMITTER: Moodie JE

PROVIDER: S-EPMC10055068 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Moodie Joanna E JE Harris Sarah E SE Harris Mathew A MA Buchanan Colin R CR Davies Gail G Taylor Adele A Redmond Paul P Liewald David D Del C Valdés Hernández Maria M Shenkin Susan S Russ Tom C TC Muñoz Maniega Susana S Luciano Michelle M Corley Janie J Stolicyn Aleks A Shen Xueyi X Steele Douglas D Waiter Gordon G Sandu-Giuraniuc Anca A Bastin Mark E ME Wardlaw Joanna M JM McIntosh Andrew A Whalley Heather H Tucker-Drob Elliot M EM Deary Ian J IJ Cox Simon R SR

bioRxiv : the preprint server for biology 20230920

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regul ...[more]

PMID: 36993650

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Project description:IntroductionStudies have shown age-related differences in numerical cognition, for example, in the level of numerosity comparison ability. Moreover, some studies point out individual differences in the cognitive strategies employed during the performance of numerosity comparison tasks and reveal that they are related to the aging process. One probable cause of these differences is the level of cognitive functioning. The aim of our study was to determine the relationships among numerosity comparison ability, the cognitive strategies utilized in the performance of numerosity comparison tasks and the general cognitive functioning in older people.MethodsForty-seven elderly people participated in the study. The participants were examined using overall cognitive functioning scales and computerized numerosity comparison task.ResultsThe results showed many correlations between the participants' level of cognitive functioning and the percent of correct responses (PCR) and response time (RT) during numerosity comparison, as well as with the cognitive strategies applied by the participants. Task correctness was positively related to the level of performance in the attention and executive function tasks. In contrast, the long-term memory resources index and visuospatial skills level were negatively correlated with RT regarding numerosity comparison task performance. The level of long-term memory resources was also positively associated with the frequency of use of more complex cognitive strategies. Series of regression analyses showed that both the level of general cognitive functioning and the cognitive strategies employed by participants in numerosity comparison can explain 9-21 percent of the variance in the obtained results.DiscussionIn summary, these results showed significant relationships between the level of cognitive functioning and proficiency in numerosity comparison measured in older people. Moreover, it has been shown that cognitive resources level is related to the strategies utilized by older people, which indicates the potential application for cognitive strategy examinations in the development of new diagnostic tools.

Project description:Subcortical ischemic stroke can lead to persistent structural changes in the cerebral cortex. The evolution of cortical structural changes after subcortical stroke is largely unknown, as are their relations with motor recovery, lesion location, and early impairment of specific subsets of fibers in the corticospinal tract (CST). In this observational study, cortical structural changes were compared between 181 chronic patients with subcortical stroke involving the motor pathway and 113 healthy controls. The impacts of acute lesion location and early impairments of specific CSTs on cortical structural changes were investigated in the patients by combining voxel-based correlation analysis with an association study that compared CST damage and cortical structural changes. Longitudinal patterns of cortical structural change were explored in a group of 81 patients with subcortical stroke using a linear mixed-effects model. In the cross-sectional analyses, patients with partial recovery showed more significant reductions in cortical thickness, surface area, or gray matter volume in the sensorimotor cortex, cingulate gyrus, and gyrus rectus than did patients with complete recovery; however, patients with complete recovery demonstrated more significant increases in the cortical structural measures in frontal, temporal, and occipital regions than did patients with partial recovery. Voxel-based correlation analysis in these patients showed that acute stroke lesions involving the CST fibers originating from the primary motor cortex were associated with cortical thickness reductions in the ipsilesional motor cortex in the chronic stage. Acute stroke lesions in the putamen were correlated with increased surface area in the temporal pole in the chronic stage. The early impairment of the CST fibers originating from the primary sensory area was associated with increased cortical thickness in the occipital cortex. In the longitudinal analyses, patients with partial recovery showed gradually reduced cortical thickness, surface area, and gray matter volume in brain regions with significant structural damage in the chronic stage. Patients with complete recovery demonstrated gradually increasing cortical thickness, surface area, and gray-matter volume in the frontal, temporal, and occipital regions. The directions of slow structural changes in the frontal, occipital, and cingulate cortices were completely different between patients with partial and complete recovery. Complex cortical structural changes and their dynamic evolution patterns were different, even contrasting, in patients with partial and complete recovery, and were associated with lesion location and with impairment of specific CST fiber subsets.

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General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Publications

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

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