Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.12.20.572617

Using Machine Learning to Identify Neural Mechanisms Underlying the Development of Cognition in Children and Adolescents with ADHD

Abstract

Children and adolescents diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) often show deficits in various measures of higher-level cognition, such as, memory and executive functioning. Poorer high-level cognitive functioning in children with ADDH has been associated with differences in functional connectivity across the brain, including the frontoparietal network. However, little is known about the developmental changes to cortical functional connectivity profiles associated with higher-order cognitive abilities in this cohort. To characterize changes in the functional brain connectivity profiles related to higher-order cognitive functioning, we analyzed a large dataset(n=479) from the publicly available Healthy Brain Network which included fMRI data collected while children and adolescents between the ages of 6 and 16 watched a short movie-clip. The cohort was divided into two groups, neurotypical youth (n=106), and children and adolescents with ADHD (n=373). We applied machine learning models to functional connectivity profiles generated from the fMRI data to identify patterns of network connectivity that differentially predict cognitive abilities in our cohort of interest. We found, using out-of-sample cross validation, models using functional connectivity profiles in response to movie-watching successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not in adolescents with ADHD. The models identified connections with the default mode, memory retrieval, and dorsal attention networks as driving prediction during early and middle childhood, but connections with the somatomotor, cingulo-opercular, and frontoparietal networks were more important in middle childhood. This work demonstrated that computational models applied to neuroimaging data in response to naturalistic stimuli can identify distinct neural mechanisms associated with cognitive abilities at different developmental stages in children and adolescents with ADHD.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pho, B., Stevenson, R., Mohsenzadeh, Y., Stojanoski, B.. 2023-12-21. Using Machine Learning to Identify Neural Mechanisms Underlying the Development of Cognition in Children and Adolescents with ADHD. https://doi.org/10.1101/2023.12.20.572617

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Functional validation of allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic option for Autosomal Dominant Leukodystrophy

Adult-onset Autosomal Dominant Leukodystrophy (ADLD) is a rare fatal leukodystrophy caused by increased LMNB1 gene dosage, most commonly resulting from duplication of the LMNB1 locus. Because ADLD is a gene dosage disorder, selective reduction of pathological LMNB1 expression represents a rational therapeutic strategy. Although allele-specific RNA interference has previously been shown to lower LMNB1 levels in patient-derived fibroblasts and directly reprogrammed neurons, its therapeutic effects have not been evaluated in disease-relevant human glial cells or using functional efficacy endpoints. Here, we established human induced pluripotent stem cell-derived astrocytes from ADLD patients as a human glial model in which to validate allele-specific LMNB1 silencing across molecular, cellular, and functional readouts. ADLD astrocytes recapitulated increased LMNB1 expression and characteristic nuclear abnormalities and displayed transcriptional alterations affecting extracellular matrix organization, calcium homeostasis, metabolism and RNA processing. Functionally, these cells also exhibited functional phenotypes suitable for therapeutic evaluation: astrocyte-conditioned medium impaired the viability of both murine and human oligodendroglial cultures, while conditioned-medium and direct astrocyte-seeding paradigms revealed impaired post-lesion myelin recovery in lysolecithin-treated cerebellar organotypic slices. Allele-specific LMNB1 silencing restored physiological LMNB1 levels, corrected nuclear abnormalities, attenuated astrocyte-mediated oligodendroglial toxicity, improved post-lesion myelin recovery, and was associated with selective transcriptional programs associated with extracellular support and cholesterol metabolism. Together, these findings provide molecular, cellular, and functional validation of allele-specific LMNB1 dosage correction in patient-derived human astrocytes and offer key support for LMNB1-lowering strategies in disease-relevant human glial cells.

neuroscience↗

Perceptual integration of multisensory haptic, visual, and auditory feedback for roughness discrimination in augmented reality

Understanding how our different senses interact to shape our perception is essential to design realistic and immersive virtual and augmented reality (VR/AR) experiences. The present study investigated how roughness perception can be modulated through haptic, visual, and auditory cues in AR using a vibrotactile wristband. Participants compared virtual textures varying in vibration frequency/amplitude, visual grain size, and friction sound. Results revealed strong linear relationships between stimulus parameters and perceived roughness, with haptic frequency and visual cues driving the highest discrimination performance. Adding non-informative sensory feedback reduced perceptual sensitivity, acting as noise. Individual differences emerged: participants who rated haptic as the easiest modality showed greater sensitivity to haptic variations, while visual-reliant participants performed better with visual cues. We conclude that roughness in AR can be systematically manipulated, but is vulnerable to perceptual interference from irrelevant inputs, where our work provides actionable insights for implementing optimized and adaptive AR/VR interfaces.

neuroscience↗

Structural and functional MRI signatures of Gambling Disorder: a case-control study

Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.

neuroscience↗