Biology subjects

Moqadam, R.

Publications and source records attributed to Moqadam, R..

3 recordsLinked to original sources

bioRxiv2024

Beyond brain size: disentangling the effect of sex and brain size on brain morphometry and cognitive functioning

It is imperative to study sex differences in brain morphology and function. However, there are major observable and unobservable confounding factors that can contribute to the estimated differences. Males have larger head sizes than females. Head size differences not only act as a confounding factor in studying sex differences in the brain, but also impact its anatomy and functioning. In this work, we seek to disentangle the effect of head size from sex in studying sex differentiated aging trajectories, its relation to canonical functional networks and cytoarchitectural classes, brain allometry, cognition. Using the UK Biobank (UKBB) neuroimaging data (N = 35,732 participants, 19,281 females, 44-82 years of age), we created a subsample (N = 11,294) where females (N = 5,657) and males were matched by their total intracranial volume (TIV) and age, a subsample that maintains the UKBB sample distribution, one matched only by age, and one that exaggerated the TIV difference between sexes. We then modeled the aging trajectories at both regional and vertex-wise levels in the four subsamples, and compared the estimations of the models. Our results show that when females and males have the same head size, the overall sex estimations tend towards zero, suggesting that most of the variability results from head size differences. Our approach also revealed bidirectional sex differences in brain neuroanatomy previously masked by the effect of head size. Further, the scaling relationship between regional and total brain volume remains fairly consistent across the lifespan and is not sex differentiated overall. We evaluated how the results of cognitive tests with perceived sex differences are influenced and explained by head size and found that although the correlation between TIV and cognitive scores is low, the matching process changes the direction of the effect sizes of differences between sexes in "verbal and numerical reasoning" and "working memory" cognitive domains. Taken together, employing a matching approach that is widely used in causal modeling studies, we provide new evidence for disentanglement of sex differences in the brain from head size as a biological confound.

neuroscience↗

bioRxiv2024

The Douglas Bell Canada Brain Bank Post-mortem Brain Imaging Protocol

Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Postmortem MRIs can provide complementary anatomical and microstructural information to in vivo imaging and ex vivo neuropathological assessments without compromising the sample for future investigations. We have developed a postmortem MRI protocol for the brain specimens of the Douglas-Bell Canada Brain Bank (DBCBB), the largest brain bank in Canada housing over 3000 neurotypical and diseased brain specimens, that allows for acquisition of high-resolution 3T and 7T MRIs. Our protocol can be used to scan DBCBB specimens with minimal tissue manipulation, allowing for feasibly scanning large numbers of postmortem specimens while retaining the quality of the tissue for downstream histology and immunohistochemistry assessments. We demonstrate the robustness of this protocol in spite of the dependency of image quality on fixation by acquiring data on the first day of extraction and fixation, to over twenty years post fixation. The acquired images can be used to perform volumetric segmentations, cortical thickness measurements, and quantitative analyses which can be potentially used to link MRI-derived and ex vivo histological measures, assaying both the normative organization of the brain and ex vivo measures of pathology.

neuroscience↗

bioRxiv2023

Investigating the impact of motion in the scanner on brain age predictions

IntroductionBrain Age Gap (BAG) is defined as the difference between the brains predicted age and the chronological age of an individual. Magnetic resonance imaging (MRI)-based BAG can quantify acceleration of brain aging, and is used to infer brain health as aging and disease interact. Motion in the scanner is a common occurrence that can affect the acquired MRI data and act as a major confound in the derived models. As such, age-related changes in head motion may impact the observed age-related differences. However, the relationship between head motion and BAG as estimated by structural MRI has not been systematically examined. The aim of this study is to assess the impact of motion on voxel-based morphometry (VBM) based BAG. MethodsData were obtained from two sources: i) T1-weighted (T1w) MRIs from the Cambridge Centre for Ageing and Neuroscience (CamCAN) were used to train the brain age prediction model, and ii) T1w MRIs from the Movement-related artifacts (MR-ART) dataset were used to assess the impact of motion on BAG. MR-ART includes one motion-free and two motion-affected (one low and one high) 3D T1w MRIs. We also visually rated the motion levels of the MR-ART MRIs from 0 to 5, with 0 meaning no motion and 5 high motion levels. All images were pre-processed through a standard VBM pipeline. GM density across cortical and subcortical regions were then used to train the brain age prediction model and assess the relationship between BAG and MRI motion. Principal component analysis was used to perform dimension reduction and extract the VBM-based features. BAG was estimated by regressing out the portion of delta age explained by chronological age. Linear mixed effects models were used to investigate the relationship between BAG and motion session as well as motion severity, including participant IDs as random effects. We repeated the same analysis using cortical thickness based on FreeSurfer 7.4.1 and to compare the results for volumetric versus surface-based measures of brain morphometry. ResultsIn contrast with the session with no induced motion, predicted delta age was significantly higher for high motion sessions 2.35 years (t = 5.17, p < 0.0001), with marginal effect for low motion sessions 0.95 years (t = 2.11, p=0.035) for VBM analysis as well as 3.46 years (t = 11.45, p < 0.0001) for high motion and 2.28 years (t = 7.54, p<0.0001) for low motion based on cortical thickness. In addition, delta age was significantly associated with motion severity as evaluated by visual rating 0.45 years per rating level (t = 4.59, p < 0.0001) for VBM analysis and 0.83 years per motion level (t = 12.89, p<0.0001) for cortical thickness analysis. ConclusionMotion in the scanner can significantly impact brain age estimates, and needs to be accounted for as a confound, particularly when studying populations that are known to have higher levels of motion in the scanner. These results have significant implications for brain age studies in aging and neurodegeneration. Based on these findings, we recommend assessment and inclusion of visual motion ratings in such studies. In cases that the visual rating proves prohibitive, we recommend the inclusion of normalized Euler number from FreeSurfer as defined in the manuscript as a covariate in the models.

neuroscience↗