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Meng-Chuan Lai

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YNIMG Journal 2023 Journal Article

Systematic comparisons of different quality control approaches applied to three large pediatric neuroimaging datasets

  • Hajer Nakua
  • Colin Hawco
  • Natalie J. Forde
  • Michael Joseph
  • Maud Grillet
  • Delaney Johnson
  • Grace R. Jacobs
  • Sean Hill

Introduction Poor quality T1-weighted brain scans systematically affect the calculation of brain measures. Removing the influence of such scans requires identifying and excluding scans with noise and artefacts through a quality control (QC) procedure. While QC is critical for brain imaging analyses, it is not yet clear whether different QC approaches lead to the exclusion of the same participants. Further, the removal of poor-quality scans may unintentionally introduce a sampling bias by excluding the subset of participants who are younger and/or feature greater clinical impairment. This study had two aims: (1) examine whether different QC approaches applied to T1-weighted scans would exclude the same participants, and (2) examine how exclusion of poor-quality scans impacts specific demographic, clinical and brain measure characteristics between excluded and included participants in three large pediatric neuroimaging samples. Methods We used T1-weighted, resting-state fMRI, demographic and clinical data from the Province of Ontario Neurodevelopmental Disorders network (Aim 1: n = 553, Aim 2: n = 465), the Healthy Brain Network (Aim 1: n = 1051, Aim 2: n = 558), and the Philadelphia Neurodevelopmental Cohort (Aim 1: n = 1087; Aim 2: n = 619). Four different QC approaches were applied to T1-weighted MRI (visual QC, metric QC, automated QC, fMRI-derived QC). We used tetrachoric correlation and inter-rater reliability analyses to examine whether different QC approaches excluded the same participants. We examined differences in age, mental health symptoms, everyday/adaptive functioning, IQ and structural MRI-derived brain indices between participants that were included versus excluded following each QC approach. Results Dataset-specific findings revealed mixed results with respect to overlap of QC exclusion. However, in POND and HBN, we found a moderate level of overlap between visual and automated QC approaches (rtet=0. 52–0. 59). Implementation of QC excluded younger participants, and tended to exclude those with lower IQ, and lower everyday/adaptive functioning scores across several approaches in a dataset-specific manner. Across nearly all datasets and QC approaches examined, excluded participants had lower estimates of cortical thickness and subcortical volume, but this effect did not differ by QC approach. Conclusion The results of this study provide insight into the influence of QC decisions on structural pediatric imaging analyses. While different QC approaches exclude different subsets of participants, the variation of influence of different QC approaches on clinical and brain metrics is minimal in large datasets. Overall, implementation of QC tends to exclude participants who are younger, and those who have more cognitive and functional impairment. Given that automated QC is standardized and can reduce between-study differences, the results of this study support the potential to use automated QC for large pediatric neuroimaging datasets.

YNICL Journal 2021 Journal Article

Sex/gender differences in the human autistic brains: A systematic review of 20 years of neuroimaging research

  • Kelly Mo
  • Tara Sadoway
  • Sarah Bonato
  • Stephanie H. Ameis
  • Evdokia Anagnostou
  • Jason P. Lerch
  • Margot J. Taylor
  • Meng-Chuan Lai

Our current understanding of autism is largely based on clinical experiences and research involving male individuals given the male-predominance in prevalence and the under-inclusion of female individuals due to small samples, co-occurring conditions, or simply being missed for diagnosis. There is a significantly biased 'male lens' in this field with autistic females insufficiently understood. We therefore conducted a systematic review to examine how sex and gender modulate brain structure and function in autistic individuals. Findings from the past 20 years are yet to converge on specific brain regions/networks with consistent sex/gender-modulating effects. Despite at least three well-powered studies identifying specific patterns of significant sex/gender-modulation of autism-control differences, many other studies are likely underpowered, suggesting a critical need for future investigation into sex/gender-based heterogeneity with better-powered designs. Future research should also formally investigate the effects of gender, beyond biological sex, which is mostly absent in the current literature. Understanding the roles of sex and gender in the development of autism is an imperative step to extend beyond the 'male lens' in this field.

YNICL Journal 2020 Journal Article

Beyond diagnosis: Cross-diagnostic features in canonical resting-state networks in children with neurodevelopmental disorders

  • Eun Jung Choi
  • Marlee M. Vandewouw
  • Margot J. Taylor
  • Paul D. Arnold
  • Jessica Brian
  • Jennifer Crosbie
  • Elizabeth Kelley
  • Meng-Chuan Lai

Children with neurodevelopmental disorders (NDDs) share common behavioural manifestations despite distinct categorical diagnostic criteria. Here, we examined canonical resting-state network connectivity in three diagnostic groups (autism spectrum disorder, attention-deficit/hyperactivity disorder and paediatric obsessive-compulsive disorder) and typically developing controls (TD) in a large single-site sample (N = 407), applying diagnosis-based and dimensional approaches to understand underlying neurobiology across NDDs. Each participant's functional network graphs were computed using five graph metrics. In diagnosis-based comparisons, an analysis of covariance was performed to compare all NDDs to TD, followed by pairwise comparisons between NDDs. In the dimensional approach, participants' functional network graphs were correlated with continuous behavioural measures, and a data-driven k-means clustering analysis was applied to determine if subgroups of participants were seen, without diagnostic information having been included. In the diagnosis-based comparisons, children with NDDs did not differ significantly from the TD group and the NDD categorical groups also did not differ significantly from each other, across all graph metrics. In the dimensional, diagnostic-independent approach, however, subcortical functional connectivity was significantly correlated with participants' general adaptive functioning across all participants. The clustering analysis identified an optimal solution of two clusters, and participants assigned in the same data-driven cluster were highly heterogeneous in diagnosis. Neither cluster exclusively contained a specific diagnostic group, nor did NDDs separate cleanly from TDs. Each participant's distance ratio between the two clusters was significantly correlated with general adaptive functioning, social deficits and attentional problems. Our results suggest the neurobiological similarity and dissimilarity between NDDs need to be investigated beyond DSM/ICD-based, behaviourally-defined diagnostic categories.

YNICL Journal 2020 Journal Article

Greater Individual Variability in Functional Brain Activity during Working Memory Performance in young people with Autism and Executive Function Impairment

  • Colin Hawco
  • Laagishan Yoganathan
  • Aristotle N. Voineskos
  • Rachael Lyon
  • Thomas Tan
  • Zafiris J. Daskalakis
  • Daniel M. Blumberger
  • Paul E. Croarkin

Individuals with autism spectrum disorder (ASD) often present with executive functioning (EF) deficits, including spatial working memory (SWM) impairment, which impedes real-world functioning. The present study examined task-related brain activity, connectivity and individual variability in fMRI-measured neural response during an SWM task in older youth and young adults with autism and clinically significant EF impairment. Neuroimaging was analyzed in 29 individuals with ASD without intellectual disability who had clinically significant EF impairment on the Behavior Rating Inventory of Executive Function, and 20 typically developing controls (participant age range=16-34). An SWM N-Back task was performed during fMRI. SWM activity (2-Back vs. 0-Back) and task-related dorsolateral prefrontal cortex (DLPFC) connectivity was examined within and between groups. Variability of neural response during SWM was also examined. During SWM performance both groups activated the expected networks, and no group differences in network activation or task-related DLPFC-connectivity were found. However, greater individual variability in the pattern of SWM activity was found in the ASD versus the typically developing control group. While there were no group differences in SWM task-evoked activity or connectivity, fronto-parietal network engagement was found to be more variable/idiosyncratic in ASD. Our results suggest that the fronto-parietal network may be shifted or sub-optimally engaged during SWM performance in participants with ASD with clinically significant EF impairment, with implications for developing targeted interventions for this subgroup.

YNIMG Journal 2012 Journal Article

Individual differences in brain structure underpin empathizing–systemizing cognitive styles in male adults

  • Meng-Chuan Lai
  • Michael V. Lombardo
  • Bhismadev Chakrabarti
  • Christine Ecker
  • Susan A. Sadek
  • Sally J. Wheelwright
  • Declan G.M. Murphy
  • John Suckling

Individual differences in cognitive style can be characterized along two dimensions: ‘systemizing’ (S, the drive to analyze or build ‘rule-based’ systems) and ‘empathizing’ (E, the drive to identify another's mental state and respond to this with an appropriate emotion). Discrepancies between these two dimensions in one direction (S>E) or the other (E>S) are associated with sex differences in cognition: on average more males show an S>E cognitive style, while on average more females show an E>S profile. The neurobiological basis of these different profiles remains unknown. Since individuals may be typical or atypical for their sex, it is important to move away from the study of sex differences and towards the study of differences in cognitive style. Using structural magnetic resonance imaging we examined how neuroanatomy varies as a function of the discrepancy between E and S in 88 adult males from the general population. Selecting just males allows us to study discrepant E-S profiles in a pure way, unconfounded by other factors related to sex and gender. An increasing S>E profile was associated with increased gray matter volume in cingulate and dorsal medial prefrontal areas which have been implicated in processes related to cognitive control, monitoring, error detection, and probabilistic inference. An increasing E>S profile was associated with larger hypothalamic and ventral basal ganglia regions which have been implicated in neuroendocrine control, motivation and reward. These results suggest an underlying neuroanatomical basis linked to the discrepancy between these two important dimensions of individual differences in cognitive style.

v2026.09.13