Biology subjects

Boraxbekk, C.-J.

Publications and source records attributed to Boraxbekk, C.-J..

6 recordsLinked to original sources

bioRxiv2024

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics; an international mega-analysis

Social anxiety disorder (SAD) has been associated with alterations in amygdala and hippocampal volume but there is mixed evidence for the direction of volumetric alterations. Additionally, little is known about the involvement of the distinct subfields in the pathophysiology of SAD. Volumetric data from a large multi-centre sample of 107 adult individuals with SAD and 140 healthy controls (HCs) was segmented using FreeSurfer to produce 9 amygdala and 12 hippocampal subfield volumes. Volumes were compared between groups using linear mixed-effects models adjusted for age, age-squared, sex, site and whole amygdala and hippocampal volumes. Subgroup analyses examined subfield volumes in relation to comorbid anxiety disorder, and comorbid major depressive disorder (MDD), psychotropic medication status, and symptom severity. In the full sample, SAD was associated with smaller amygdala volumes in the basal (d=-0.32, pFDR=0.022), accessory basal (d=- 0.42, pFDR=0.005) and corticoamygdaloid transition area (d=-0.37, pFDR=0.014), and larger hippocampal volume in the CA3 (d=0.34, pFDR=0.024), CA4 (d=0.44, pFDR=0.007), dentate gyrus (d=0.35, pFDR=0.022) and molecular layer (d=0.28, pFDR= 0.033), compared to HCs. SAD without comorbid anxiety, in addition, demonstrated smaller lateral amygdala (d=-0.30, pFDR=0.037) and hippocampal amygdala transition area (d=-0.33, pFDR=0.027) relative to HCs. In SAD without comorbid MDD, only the smaller accessory basal amygdala remained significant (d=-0.41, pFDR=0.017). No association was found between subfield volume and medication status or symptom severity. In conclusion, we observed distinct patterns of volumetric differences across specific amygdala and hippocampal subfields, regions that are associated with sensory information processing, threat evaluation and fear generalization. These findings suggest a possible disruption in information flow between the amygdala and hippocampal formation for fear processing in SAD.

neuroscience↗

bioRxiv2023

Accelerated brain change in healthy adults is associated with genetic risk for Alzheimer's disease and uncovers adult lifespan memory decline

Across healthy adult life our brains undergo gradual structural change in a pattern of atrophy that resembles accelerated brain changes in Alzheimers disease (AD). Here, using four polygenic risk scores for AD (PRS-AD) in a longitudinal adult lifespan sample aged 30 to 89 years (2-7 timepoints), we show that healthy individuals who lose brain volume faster than expected for their age, have a higher genetic AD risk. We first demonstrate PRS-AD associations with change in early Braak regions, namely hippocampus, entorhinal cortex, and amygdala, and find evidence these extend beyond that predicted by APOE genotype. Next, following the hypothesis that brain changes in ageing and AD are largely shared, we performed machine learning classification on brain change trajectories conditional on age in longitudinal AD patient-control data, to obtain a list of AD-accelerated features and model change in these in adult lifespan data. We found PRS-AD was associated with a multivariate marker of accelerated change in many of these features in healthy adults, and that most individuals above [~]50 years of age are on an accelerated change trajectory in AD-accelerated brain regions. Finally, high PRS-AD individuals also high on a multivariate marker of change showed more adult lifespan memory decline, compared to high PRS-AD individuals with less brain change. Our results support a dimensional account linking normal brain ageing with AD, suggesting AD risk genes speed up the shared pattern of ageing- and AD-related neurodegeneration that starts early, occurs along a continuum, and tracks memory change in healthy adults.

neuroscience↗

bioRxiv2022

Is short sleep bad for the brain? Brain structure and cognitive function in short sleepers

Many sleep less than recommended without experiencing daytime tiredness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this question using a combined cross-sectional and longitudinal sample of 47,029 participants (age 20-89 years) with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. 701 participants who reported to sleep < 6 hours did not experience daytime tiredness or sleep problems. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime tiredness and sleep problems (n = 1619) and participants sleeping the recommended 7-8 hours (n = 3754). However, both groups of short sleepers showed slightly lower general cognitive function, 0.16 and 0.19 standard deviations, respectively. Analyses using acelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income and education. The results suggest that some people can cope with less sleep without obvious negative consequences for brain morphometry, in line with a view on sleep need as individualized. Tiredness and sleep problems seem to be more relevant for brain structural differences than sleep duration per se. However, the slightly lower performance on tests of general cognitive function warrants closer examination by experimental designs in natural settings. Significance statementShort habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here we show that daytime tiredness and sleep problems are more important variables for regional brain volumes than sleep duration. However, participants sleeping < 6 hours had slightly lower scores on tests of general cognitive function. This indicates that sleep need is individual, and that sleep duration per se may be a less relevant variable for brain health than daytime tiredness and sleep problems. The association between habitual short sleep and lower scores on tests of general cogntitive function must be further scrutinized in natural settings.

neuroscience↗

bioRxiv2022

Sleep duration and brain structure - phenotypic associations and genotypic covariance

The question of how much sleep is best for the brain attracts scientific and public interest, and there is concern that insuficient sleep leads to poorer brain health. However, it is unknown how much sleep is sufficient and how much is too much. We analyzed 51,295 brain magnetic resonnance images from 47,039 participants, and calculated the self-reported sleep duration associated with the largest regional volumes and smallest ventricles relative to intracranial volume (ICV) and thickest cortex. 6.8 hours of sleep was associated with the most favorable brain outcome overall. Critical values, defined by 95% confidence intervals, were 5.7 and 7.9 hours. There was regional variation, with for instance the hippocampus showing largest volume at 6.3 hours. Moderately long sleep (> 8 hours) was more strongly associated with smaller relative volumes, thinner cortex and larger ventricles than even very short sleep (< 5 hours), but effect sizes were modest. People with larger ICV reported longer sleep (7.5 hours), so not correcting for ICV yielded longer durations associated with maximal volume. Controlling for socioeconomic status, body mass index and depression symptoms did not alter the associations. Genetic analyses showed that genes related to longer sleep in short sleepers were related to shorter sleep in long sleepers. This may indicate a genetically controlled homeostatic regulation of sleep duration. Mendelian randomization analyses did not suggest sleep duration to have a causal impact on brain structure in the analyzed datasets. The findings challenge the notion that habitual short sleep is negatively related to brain structure. Significance statementAccording to consensus recommendations, adults should sleep between 7 and 9 hours to optimize their health. We found that sleeping less than the recommended amount was associated with greater regional brain volumes relative to intracranial volume, and very short sleep was only weakly related to smaller volumes. Genetic analyses did not show causal effects of sleep duration on brain structure. Taken together, the results suggest that habitual short sleep is not an important contributor to lower brain volumes in adults on a group level, and that large individual dfferences in sleep need likely exist.

neuroscience↗

bioRxiv2022

Brain aging differs with cognitive ability regardless of education

Higher general cognitive ability (GCA) is associated with lower risk of neurodegenerative disorders, but neural mechanisms are unknown. GCA could be associated with more cortical tissue, from young age, i.e. brain reserve, or less cortical atrophy in adulthood, i.e. brain maintenance. Controlling for education, we investigated the relative association of GCA with reserve and maintenance of cortical volume, -area and -thickness through the adult lifespan, using multiple longitudinal brain imaging cohorts (n = 3327, 7002 MRI scans, baseline age 20-88 years, followed-up up to 11 years). There were widespread positive relationships between GCA and cortical characteristics (level-level associations). In select regions, higher baseline GCA was associated with less atrophy over time (level-change associations). Relationships remained when controlling for polygenic scores for both GCA and education. Our findings suggest that higher GCA is associated with cortical volumes by both brain reserve and -maintenance mechanisms through the adult lifespan.

neuroscience↗

bioRxiv2019

Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field strength, we performed 1H-MRS in 60 healthy volunteers to asses age-related differences in neuron- and glia-related metabolite levels and their relation to cognitive ageing. Gender was balanced and participants were assigned to a younger, middle and older group according to their age, ranging from 18 to 79 years. They underwent 1H-MRS of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus and thalamus and performed a visuo-spatial working memory task outside the scanner. Multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all brain regions of interest. Considering specific metabolites, elevated levels of glia-related metabolites in older age groups were observed in all brain regions. For the neuron-related metabolites, differences among age groups were only observed in two regions. We found higher levels of total N-acetyl aspartate in hippocampus for the older than the middle group, and lower levels of glutamate in DLPFC in the older than the younger group. Working memory performance correlated negatively with levels of glia-related metabolites for total creatine and total choline in ACC and myo-inositol in hippocampus and thalamus, but not with neuron-related metabolites. Together, the results show that age effects on glia-related metabolites scale with cognitive ageing in multiple brain regions. We conclude that 1H-MRS-derived glia-related markers may be of value in longitudinal studies of brain ageing. Significance statementNeurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. Due to the higher spectral resolution and sensitivity, 7 tesla 1H-MRS has potential to improve consistency of the results. Here we apply this technique to demonstrate that glia-related metabolites are elevated in older age in anterior cingulate cortex, hippocampus and thalamus with a novel link to cognitive ageing of visuo-spatial working memory. This study is the first to investigate normal ageing in these brain regions using 7 tesla 1H-MRS and the results indicate that glia-related metabolites could be of value in longitudinal studies of cognitive ageing.

neuroscience↗