Biology subjects

Chechlacz, M.

Publications and source records attributed to Chechlacz, M..

4 recordsLinked to original sources

bioRxiv2023

Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Education is often used as a surrogate measure of so called cognitive reserve (CR) benefiting cognitive functioning in later years. In line with Robertsons theory we tested here a hypothesis that education acting on the noradrenergic system strengthen the right fronto-parietal networks to facilitate CR and maintain cognition throughout the lifetime. We used machine learning and mediation analysis to model interactions between neurobiological features (genetic variants in noradrenergic signalling, structural and functional fronto-parietal connectivity) and education (proxy of CR) on cognitive outcomes (general cognitive ability score) in the UK Biobank cohort. We show that: (1) interactions between education and neurobiological variables better explain cognitive outcomes than either factor alone; (2) among the neurobiological features selected using variable importance testing, measures of right fronto-parietal connectivity are the strongest mediators of the effect of education on cognitive outcomes. Our findings offer novel insights into neurobiological basis of CR by pointing to between-networks connectivity, representing connections linking the default mode network with the right fronto-parietal network as the key facilitator of CR.

neuroscience↗

bioRxiv2023

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

Chronotype impacts numerous physiological and disease traits, from metabolic syndrome to schizophrenia. The suprachiasmatic nucleus (SCN) maintains transcriptional-translational feedback loop (TTFL) which acts as a central chronobiological pacemaker, regulating 24-hour cycles throughout the human body. However, each tissue maintains its own peripheral clock, and both endogenous hormones and neurotransmitters and exogenous environmental cues regulate the SCNs central clock. The extent to which brain regions outside the SCN influence the core TTFL is unknown. Here, we investigated how genetic variability affecting brain regions outside the SCN may indirectly influence chronotype, using Mendelian randomization and causal inference. We performed genome wide association studies (GWAS) based on image derived phenotypes (IDPs) from neuroimaging data (grey matter volume, thickness and surface area, microstructural white matter measures; 42,062 participants), and additionally for sleep duration and morning/evening chronotype (361,739 participants). Significant, single nucleotide polymorphisms (SNPs) associating with each phenotype were entered into 2-sample Mendelian randomization performed using inverse-variance weighted methods (exposure versus outcome): 1) chronotype versus each IDP, 2) sleep versus each IDP and 3) each IDP versus chronotype. Subsequently, we investigated genes where significant instrumental SNPs were located for circadian periodic cycling, interaction with TTFL genes in common biological pathways (genetic, physical, or functional interaction), and enrichment of traits from UK Biobank and GWAS Catalogs. We found three associations with chronotype (morning/evening diurnal preference) outside the SCN based on genetically predicted (FAM76B, DENND1A, CDH11) regional differences in brain volume. Specifically, genetically predicted lower inferior temporal gyrus volume linked to morning phenotype, while lower volume of the superior parietal lobule and angular gyrus linked to evening preference. In addition, evening chronotype exposure influenced superior temporal gyrus volume, and both increased sleep duration and evening chronotype influenced thalamic volume. We conclude that genetically mediated associations between chronotype and brain regions outside SCN exist suggesting novel zeitgeber mechanisms.

neuroscience↗

bioRxiv2021

Right fronto-parietal networks mediate the neurocognitive benefits of enriched environments.

Exposure to enriched environments (EE) throughout a lifetime, providing so called reserve, protects against cognitive decline in later years. It has been hypothesised that high levels of alertness necessitated by EE might strengthen the right fronto-parietal networks (FPN) to facilitate this neurocognitive resilience. We have previously shown that EE offset age-related deficits in selective attention by preserving grey matter within right fronto-parietal regions. Here, using neurite orientation dispersion and density imaging (NODDI), we examined the relationship between EE, microstructural properties of fronto-parietal white matter association pathways (three branches of the superior longitudinal fasciculus, SLF), structural brain health (atrophy), and attention (alertness, orienting and executive control) in a group of older adults. We show that EE is associated with a lower orientation dispersion index (ODI) within the right SLF1 which in turn mediates the relationship between EE and alertness, as well as grey- and white-matter atrophy. This suggests that EE may induce white matter plasticity (and prevent age-related dispersion of axons) within the right FPN to facilitate the preservation of neurocognitive health in later years.

neuroscience↗

bioRxiv2021

The Association Between Poor Sleep and Accelerated Brain Ageing

The ageing brain undergoes widespread gray (GM) and white matter (WM) degeneration. But numerous studies indicate large heterogeneity in the age-related brain changes, which can be attributed to modifiable lifestyle factors, including sleep. Inadequate sleep has been previously linked to GM atrophy and WM changes. However, the reported findings are highly inconsistent. By contrast to previous research independently characterizing patterns of either the GM or the WM changes, we used here linked independent component analysis (FLICA) to examine covariation in GM and WM in a group of older adults. Next, we employed a novel technique to estimate the brain age delta (i.e. difference between chronological and apparent brain age assessed using neuroimaging data) and study its associations with sleep quality and sleep fragmentation, hypothesizing that poor sleep accelerates brain ageing. FLICA revealed a number of multimodal (including both GM and WM) neuroimaging components, associated with age, but also with sleep quality and sleep fragmentation. Brain age delta estimates were highly sensitive in detecting the effects of sleep problems on the ageing brain. Specifically, we show significant associations between brain age delta and poor sleep quality, suggesting two years deviation above the chronological age. Our findings indicate that sleep problems in healthy older adults should be considered a risk factor for accelerated brain ageing.

neuroscience↗