Higher-order Processes Research Articles

Temporally dissociable neural representations of pitch height and chroma.

The extraction and analysis of pitch underpin speech and music recognition, sound segregation, and other auditory tasks. Perceptually, pitch can be represented as a helix composed of two factors: height monotonically aligns with frequency, while chroma cyclically repeats at doubled frequencies. Although the early perceptual and neurophysiological mechanisms for extracting pitch from acoustic signals have been extensively investigated, the equally essential subsequent stages that bridge to high-level auditory cognition remain less well understood. How does the brain represent perceptual attributes of pitch at higher-order processing stages and how are the neural representations formed over time? We used a machine learning approach to decode time-resolved neural responses of human listeners (10 females and 7 males) measured by magnetoencephalography across different pitches, hypothesizing that different pitches sharing similar neural representations would result in reduced decoding performance. We show that pitch can be decoded from lower-frequency neural responses within auditory-frontal cortical regions. Specifically, linear mixed-effect modeling reveals that height and chroma explain decoding performance of delta band (0.5-4 Hz) neural activity at distinct latencies: a long-lasting height effect precedes a transient chroma effect, followed by a recurrence of height after chroma, indicating sequential processing stages associated with unique perceptual and neural characteristics. Furthermore, the localization analyses of the decoder demonstrate that height and chroma are associated with overlapping cortical regions, with differences observed in the right orbital and polar frontal cortex. The data provide a perspective motivating new hypotheses on the mechanisms of pitch representation.Significance Statement Pitch is fundamental to various facets of human hearing, including music appreciation, speech comprehension, vocal learning, and sound source differentiation. How does the brain encode the perceptual features of pitch? By applying machine learning techniques to time-resolved neuroimaging data of individuals listening to different pitches, our findings reveal that pitch height and chroma-two distinct features of pitch-are associated with different neural dynamics within the auditory-frontal cortical network, with height playing a more prominent role. This offers a unified theoretical framework for understanding the perceptual and neural characteristics of pitch perception and opens new avenues for noninvasively decoding human auditory perception to develop brain-computer interfaces.

Mind in others' shoes: Neuroscientific protocol for external referent decision awareness (ERDA) in organizations.

This study investigates the neural and physiological mechanisms underlying External Referent Decision Awareness (ERDA) within organizational contexts, focusing on hierarchical roles (Head, Peer, Staff). Twenty-two professionals participated, and electroencephalographic (EEG frequency band: Delta, Theta, Alpha, Beta, Gamma) and autonomic indices (skin conductance and cardiovascular indices) were recorded, while personality traits and decision-making styles were assessed. Results revealed higher Delta and Theta activation in the left temporo-parietal junction (TPJ) during Peer-related decisions, reflecting increased social cognition and ambiguity regulation in those contexts. Gamma activity, associated with high-order cognitive processes, was prominent in the left frontal cortex across all roles, indicating complex decision evaluation. These findings underscore the complexity of low-frequency bands (Delta and Theta), involved in emotional regulation and social cognition, while high-frequency bands (Gamma) reflect cognitive integration and decision complexity. Furthermore, autonomic data showed higher Skin Conductance Levels (SCL) for Head decisions, suggesting greater emotional involvement.The findings revealed a significant negative correlation between avoidant decision-making styles and the neural and behavioral evaluations of leader decisions, suggesting reduced engagement of neurocognitive systems involved in reward processing and evaluative judgment in individuals with a tendency to avoid decision-making. Additionally, higher extraversion correlated with more favorable evaluations of decisions made by Staff, potentially indicating greater activation in neural circuits associated with social reward and group dynamics. In conclusion, these findings suggest that neural activity and personality traits interact to shape hierarchical decision-making awareness, highlighting the need for tailored leadership and decision-making strategies in organizations.

High-resolution awake mouse fMRI at 14 tesla.

High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts. Using a 14 T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100 µm×100 µm×200 µm resolution with a 2 s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust blood oxygen level-dependent (BOLD) responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 s prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous exposure of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.

The added value of metadata on test completion time for the quantification of cognitive functioning in survey research.

Information on the time spent completing cognitive testing is often collected, but such data are not typically considered when quantifying cognition in large-scale community-based surveys. We sought to evaluate the added value of timing data over and above traditional cognitive scores for the measurement of cognition in older adults. We used data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study (N = 4,091), to assess the added value of timing data over and above traditional cognitive scores, using item-specific regression models for 36 cognitive test items. Models were adjusted for age, gender, interviewer, and item score. Compared to Quintile 3 (median time), taking longer to complete specific items was associated (p < 0.05) with lower cognitive performance for 67% (Quintile 5) and 28% (Quintile 4) of items. Responding quickly (Quintile 1) was associated with higher cognitive performance for 25% of simpler items (e.g., orientation for year), but with lower cognitive functioning for 63% of items requiring higher-order processing (e.g., digit span test). Results were consistent in a range of different analyses adjusting for factors including education, hearing impairment, and language of administration and in models using splines rather than quintiles. Response times from cognitive testing may contain important information on cognition not captured in traditional scoring. Incorporation of this information has the potential to improve existing estimates of cognitive functioning.

Higgs boson production at μ+μ+ colliders

We study Higgs boson production at μ+μ+ colliders at high energy. Since both initial-state particles are positively charged, there is no W boson fusion at the leading order, as it requires a W+W− pair. However, we find that the cross section of the higher-order, γ-and Z-mediated W boson fusion process is large at high center-of-mass energies s, growing as (logs)3. This is in contrast to the logs behavior of the leading-order W boson fusion. Thus, even though it is a higher-order process, the rate of Higgs boson production for 10 TeV energies at μ+μ+ colliders with polarized beams can be as high as about half of the one at μ+μ− colliders, assuming the same integrated luminosity. To calculate the cross section of this process accurately, we carefully treat the collinear emission of the photon in the intermediate state. The thereby obtained large cross section furthermore shows the significance of Higgs production with an extra W boson in the final state also at μ+μ− and e+e− colliders. Published by the American Physical Society 2024

A novel tuning formula for PID/PIDD2 controllers for higher-order process plants

The industrial process control systems are high-order sophisticated and complicated systems with characteristics such as inertia, uncertainty, and even oscillatory. The controller design issue has long been challenging for the industry process control systems. This study proposes a novel tuning formula for PID/PIDD2 controllers for high-order process plants. Specifically, for the underdamped second-order with time delays (SOPDT) process plant, a formula for the tuning of PID/PIDD2 controller is proposed based on the relative damping coefficient x; for the critical and over-damped SOPDT process plants, the idea of using zero-pole cancellation is skillfully applied. The tuning parameters are determined by considering both robustness and integrated time absolute error (ITAE). The proposed tuning formula applies to the automatic voltage regulator (AVR) system and extends to the load frequency control (LFC) system and a practical double-capacity water tank experiment. Simulation results demonstrate that the proposed tuning method shows better robustness and anti-interference.

Case Report: A Comprehensive Early Childhood Mental Health Evaluation for Children in the Foster Care System.

Children in the foster care system often have a host of prenatal and postnatal risk factors that can compromise development including disruptions in important attachment relationships. We argue that to effectively address this complex history and inform specific recommendations for intervention, it is important for an Early Childhood Mental Health (ECMH) evaluation to include both an assessment of the caregiver-child relationship status and neurodevelopment. We describe an ECMH evaluation for a 21-month-old girl who was referred to a multidisciplinary birth to three specialty clinic for difficulties separating from her preadoptive mother, indiscriminate friendliness, and emotional and behavioral dysregulation. She had a history of prenatal substance exposure and several disruptions in important attachment relationships. We gained insight into the caregiver-child relationship through behavioral observations and used standardized testing to assess neurodevelopment. This combination of assessment techniques revealed inconsistencies in secure base attachment patterns between the parent and child. She also performed lower than what would be expected for her age across several domains of development. This case highlights a comprehensive approach to an ECMH evaluation. Recommendations for intervention prioritized the parent-child relationship given the importance of attunement between caregiver and child to first optimize stress regulation and thus set the foundation for higher-order cognitive processes to develop.

An eye-tracking and neuroimaging study of negative wording effects on cognitive load in a metacognitive awareness tool

We compared the extraneous cognitive load imposed by two wording conditions: negatively worded and non-negated items in an L2 questionnaire. The questionnaire is the metacognitive awareness listening questionnaire (MALQ), a widely used instrument for assessing metacognitive awareness strategies. Respondents' (N = 109) eye movements measured by an eye-tracker and brain activation levels measured by functional near-infrared spectroscopy (fNIRS) were obtained to examine their extraneous cognitive load in responding to MALQ. Using MANOVA, we identified distinct gaze behavior associated with negatively worded items, indicating that the presence of such items may increase extraneous cognitive load. In addition, English-as-a-second-language participants generally exhibited higher extraneous cognitive load than their L1 counterparts. The results of the neuroimaging investigation further indicated that negatively worded items require more visual attention and cognitive effort, while positively worded items may engage higher-order reflective processing in the brain, highlighting a complex interaction between attention and extraneous cognitive load. Additionally, linear mixed effects models showed that although the models under the two-wording conditions explained a significant amount of variation in respondents’ MALQ scores, they had relatively lower explanatory power (R2) though better global fit compared to the models based on the five constructs that MALQ measures (planning-evaluation, directed attention, person knowledge, mental translation, and problem-solving). We suggest that a balanced approach that considers both the target constructs and the negeative wording effect might be the most effective strategy in questionnaire design and validation. Further implications of these findings are discussed.

CESE Schemes for Solar Wind Plasma MHD Dynamics

Magnetohydrodynamic (MHD) numerical simulation has emerged as a pivotal tool in space physics research, witnessing significant advancements. This methodology offers invaluable insights into diverse space physical phenomena based on solving the fundamental MHD equations. Various numerical methods are utilized to approximate the MHD equations. Among these, the space–time conservation element and solution element (CESE) method stands out as an effective computational approach. Unlike traditional numerical schemes, the CESE method significantly enhances accuracy, even at the same base point. The concurrent discretization of space and time for conserved variables inherently achieves higher-order accuracy in both dimensions, without the need for intricate higher-order time discretization processes, which are often challenging in other methods. Additionally, this scheme can be readily extended to multidimensional cases, without relying on operator splitting or direction alternation. This paper primarily delves into the remarkable progress of CESE MHD models and their applications in studying solar wind, solar eruption activities, and the Earth’s magnetosphere. We aim to illuminate potential avenues for future solar–interplanetary CESE MHD models and their applications. Furthermore, we hope that the discussions presented in this review will spark new research endeavors in this dynamic field.

Sex differences in autism spectrum disorder using class imbalance adjusted functional connectivity

Autism spectrum disorder (ASD) is an atypical neurodevelopmental condition with a diagnostic ratio largely differing between male and female participants. Due to the sex imbalance in participants with ASD, we lack an understanding of the differences in connectome organization of the brain between male and female participants with ASD. In this study, we matched the sex ratio using a Gaussian mixture model-based oversampling technique and investigated the differences in functional connectivity between male and female participants with ASD using low-dimensional principal gradients. Between-group comparisons of the gradient values revealed significant interaction effects of sex in the sensorimotor, attention, and default mode networks. The sex-related differences in the gradients were highly associated with higher-order cognitive control processes. Transcriptomic association analysis provided potential biological underpinnings, specifying gene enrichment in the cortex, thalamus, and striatum during development. Finally, the principal gradients were differentially associated with symptom severity of ASD between sexes, highlighting significant effects in female participants with ASD. Our work proposed an oversampling method to mitigate sex imbalance in ASD and observed significant sex-related differences in functional connectome organization. The findings may advance our knowledge about the sex heterogeneity in large-scale brain networks in ASD.

The self-relevant spotlight metaphor: Self-relevant targets diminish distractor–response-binding effects

AbstractRecently, it has been proposed that self-relevance of a stimulus enhances executive control and reduces the impact of distractors on current task performance. The present study aimed to test whether the binding between a distractor and a response is influenced by self-relevance, too. We assumed that targets’ self-relevance should increase executive control processes and therefore reduce the influence of distractors on current performance. In a distractor–response-binding (DRB) task, which measures the strength of binding between distractor stimuli and responses, we varied target relevance so that participants responded to targets that either were or were not self-relevant. Our design made it possible to measure DRB effects for both relevance conditions separately. DRB effects were diminished if targets were self-relevant compared to when they were not. These results expand our understanding of the influence of self-relevance on cognitive performance. The influence of self-relevance is not purely perceptual (Sui &amp; Humphreys, 2012, Journal of Experimental Psychology: Human Perception and Performance, 38[5], 1105–1117), but also found in higher-order processes such as executive control. Moreover, whereas for different paradigms binding advantages of self-relevance are assumed (Sui &amp; Humphreys, 2015a, Trends in Cognitive Sciences, 19[12], 719–728; Humphreys &amp; Sui, 2016, Cognitive Neuroscience, 7[1/4], 5–17), this study identifies an important boundary condition, in that distractor–response binding is reduced by target self-relevance.

Whisker stimulation with different frequencies reveals non-uniform modulation of functional magnetic resonance imaging signal across sensory systems in awake rats.

Primary sensory systems are classically considered to be separate units, however there is current evidence that there are notable interactions between them. We examined the cross-sensory interplay by applying a quiet and motion-tolerant zero echo time functional magnetic resonance imaging (fMRI) technique to elucidate the evoked brain-wide responses to whisker pad stimulation in awake and anesthetized rats. Specifically, characterized the brain-wide responses in core and non-core regions to whisker pad stimulation by the varying stimulation-frequency, and determined whether isoflurane-medetomidine anesthesia, traditionally used in preclinical imaging, confounded investigations related to sensory integration. We demonstrated that unilateral whisker pad stimulation not only elicited robust activity along the whisker-mediated tactile system, but also in auditory, visual, high-order, and cerebellar regions, indicative of brain-wide cross-sensory and associative activity. By inspecting the response profiles to different stimulation frequencies and temporal signal characteristics, we observed that the non-core regions responded to stimulation in a very different way compared to the primary sensory system, likely reflecting different encoding modes between the primary sensory, cross-sensory, and integrative processing. Lastly, while the activity evoked in low-order sensory structures could be reliably detected under anesthesia, the activity in high-order processing and the complex differences between primary, cross-sensory, and associative systems were visible only in the awake state. We conclude that our study reveals novel aspects of the cross-sensory interplay of whisker-mediated tactile system, and importantly, that these would be difficult to observe in anesthetized rats.

Humor processing and its relationship with clinical features in patients with first-episode schizophrenia

Humor, a higher-order social cognitive process unique to humans, is commonly impaired in patients with chronic schizophrenia. However, humor processing and its association with the clinical characteristics in the early stage of the illness remain unknown. In this study, we investigated humor processing and its relationship with clinical features in patients with first-episode schizophrenia (FES). We recruited 45 patients with FES and 44 healthy controls matched for age, sex, and education level. The participants completed the Picture Humor Processing Task (HPT-p) and Video Humor Processing Task (HPT-v), which evaluated humor comprehension and appreciation, and a questionnaire assessing their humor styles. Clinical participants also completed clinical and social functioning measurements. Signal detection theory analysis was used to calculate the d' and β values, which represent the detection of humor signals in the comprehension phase and inner criteria of the humor appreciation phase, respectively. In the HPT-p, patients with FES showed a higher false alarm rate (p = 0.048) than healthy controls, whereas the hitting rate, signal recognition ability (d' value), and intrinsic evaluation criterion (β value) were comparable between the two participants groups. In the HPT-v, patients with FES showed lower within-group coherence in the funniness rating (p = 0.023) than healthy controls. In addition, the false alarm rate in the HPT-p and negative symptoms effectively predicted social functioning in patients with FES (R2 = 0.681, p < 0.001). Our results indicate that impairment of humor comprehension in patients with schizophrenia is generated in the first episode and contributes to social functioning deficits, which require early recognition and intervention.

Cognitive disparity in online rumor perception: a group analysis during COVID-19.

The harmonious cognitive alignment among various netizen groups is pivotal for the spread and amplification of online rumors. This alignment, characterized by shared cognitive inclinations, fosters uniformity in attitudes and perspectives, thereby precipitating synchronized engagement in the dissemination of such rumors. Notably, discernible disparities emerge in group cognition as different types of rumors pertaining to the same event propagate. This research endeavors to dissect the roles of netizen groups through the lens of cognitive variance, thereby attaining a more profound comprehension of the distinctive traits and behavioral dynamics of various netizen factions in the context of online rumor dissemination. By integrating Bloom's taxonomy and crafting a survey questionnaire, this study captured the cognitive responses of netizens to various online rumor themes across two critical dimensions: (1) Information Cognition: exploring cognitive processing levels from basic recall to application and analysis and (2) Attitude Change: evaluating higher-order cognitive processes such as evaluating and creating in response to complex rumor scenarios. The decision tree classification algorithm was meticulously applied to dissect the catalysts behind the cognitive shifts among netizens. Additionally, the K-Means clustering algorithm was effectively utilized to categorize netizen groups along thematic lines, offering a nuanced view of their cognitive engagement. The initial impression of a rumor significantly influences netizens' final cognitive perceptions. Twelve characteristics were observed in netizen groups during the dissemination of rumors on different themes, and these groups were classified into four categories: knowledge-oriented, competition-oriented, social-oriented, and entertainment-oriented, based on their cognitive differences. Throughout the lifecycle of online rumors, from inception to dissemination, diverse netizen groups assume distinct roles, each exerting a unique influence on the spread and reception of information. By implementing tailored governance strategies that are sensitive to the characteristics of these groups, it is possible to attain substantially more effective outcomes in managing the propagation of online rumors. This nuanced approach to governance recognizes the heterogeneity of the online community and leverages it to enhance the efficacy of interventions.

Noise analysis of a quasi-phase-matched quantum frequency converter and higher-order counter-propagating SPDC

Quantum frequency conversion (QFC) will be an indispensable ingredient in future quantum technologies. For example, large-scale fibre-based quantum networks will require QFC to interconnect heterogeneous building blocks like emitters, channels, memories, and detectors. The performance of existing QFC devices – typically realized in periodically poled nonlinear crystals – is often severely limited by parasitic noise that arises when the pump wavelength lies between the inter-converted wavelengths. Here we comprehensively investigate the noise spectrum of a QFC device pumped by a CW 1064 nm laser. The converter was realized as a bulk periodically poled potassium titanyl phosphate (ppKTP) crystal quasi-phase-matched for conversion between 637 nm and 1587 nm, which was also polished and coated to resonantly enhance the pump field by a factor of 50. While Raman scattering dominates the noise background from 1140 nm to 1330 nm, at larger energy shifts (beyond 60 THz), parasitic spontaneous parametric down-conversion (SPDC) is the strongest noise source. Further, the noise spectrum was contaminated by a regular succession of narrow-band peaks, which we attribute to a heretofore unidentified higher-order counter-propagating SPDC processes – with quasi-phase-matching orders up to 44 evident in our measurements. This work provides a comprehensive overview of the limiting noise sources in QFC devices that use quasi-phase-matched crystals and will prove an invaluable resource in guiding their future development.

The Spectral Representation Method: A framework for simulation of stochastic processes, fields, and waves

The Spectral Representation Method (SRM) was developed in the 1970s to simulate Gaussian stochastic processes and fields from a Fourier series expansion according to the Spectral Representation Theorem. Since those early developments, the SRM has continuously evolved into a comprehensive framework for the simulation of stochastic processes, fields, and waves with a rigorous theoretical foundation. Its major advantages are conceptual simplicity and computational efficiency. In the 1990s, much of the theory for simulation of Gaussian stochastic processes, fields, and waves was firmly established and early methods for simulation of non-Gaussian processes, fields, and waves were introduced. In the 2000s and 2010s, methods that coupled the SRM with Translation Process Theory were improved to enable efficient and accurate simulations of stochastic processes, fields, and waves with strongly non-Gaussian marginal probability distributions. More recently, the SRM was extended for higher-order non-Gaussian processes, fields, and waves by extending the Fourier stochastic expansion to include non-linear wave interactions derived from higher-order spectra. This paper reviews the key theoretical developments related with the SRM and provides the relevant algorithms necessary for its practical implementation for the simulation of stochastic processes, fields, and waves that can be either stationary or non-stationary, homogeneous or non-homogeneous, one-dimensional or multi-dimensional, scalar or multi-variate, Gaussian or non-Gaussian, or any combination thereof. The paper concludes with some brief remarks addressing the open research challenges in SRM-based theory and simulations.

Deep Learning Model for Quality Assessment of Urinary Bladder Ultrasound Images using Multi-scale and Higher-order Processing.

Autonomous Ultrasound Image Quality Assessment (US-IQA) is a promising tool to aid the interpretation by practicing sonographers and to enable the future robotization of ultrasound procedures. However, autonomous US-IQA has several challenges. Ultrasound images contain many spurious artifacts, such as noise due to handheld probe positioning, errors in the selection of probe parameters and patient respiration during the procedure. Further, these images are highly variable in appearance with respect to the individual patient's physiology. We propose to use a deep Convolutional Neural Network (CNN), USQNet, which utilizes a Multi-scale and Local-to-Global Second-order Pooling (MS-L2GSoP) classifier to conduct the sonographer-like assessment of image quality. This classifier first extracts features at multiple scales to encode the inter-patient anatomical variations, similar to a sonographer's understanding of anatomy. Then, it uses second-order pooling in the intermediate layers (local) and at the end of the network (global) to exploit the second-order statistical dependency of multi-scale structural and multi-region textural features. The L2GSoP will capture the higher-order relationships between different spatial locations and provide the seed for correlating local patches, much like a sonographer prioritizes regions across the image. We experimentally validated the USQNet for a new dataset of the human urinary bladder ultrasound images. The validation involved first with the subjective assessment by experienced radiologists' annotation, and then with state-of-the-art CNN networks for US-IQA and its ablated counterparts. The results demonstrate that USQNet achieves a remarkable accuracy of 92.4% and outperforms the SOTA models by 3 - 14% while requiring comparable computation time.

Evidence for convergence of distributed cortical processing in band-like functional zones in human entorhinal cortex

The wide array of cognitive functions associated with the hippocampus is supported through interactions with the cerebral cortex. However, most of the direct cortical input to the hippocampus originates in the entorhinal cortex, forming the hippocampal-entorhinal system. In humans, the role of the entorhinal cortex in mediating hippocampal-cortical interactions remains unknown. In this study, we used precision neuroimaging to examine the distributed cortical anatomy associated with the human hippocampal-entorhinal system. Consistent with animal anatomy, our results associate different subregions of the entorhinal cortex with different parts of the hippocampus long axis. Furthermore, we find that the entorhinal cortex comprises three band-like zones that are associated with functionally distinct cortical networks. Importantly, the entorhinal cortex bands traverse the proposed human homologs of rodent lateral and medial entorhinal cortices. Finally, we show that the entorhinal cortex is a major convergence area of distributed cortical processing and that the topography of cortical networks associated with the anterior medial temporal lobe mirrors the macroscale structure of high-order cortical processing.

Cortical Alterations Associated with Executive Function Deficits in Youth with a Congenital Heart Defect

Abstract Adolescents and young adults born with a complex congenital heart defect (CHD) are at risk for executive function (ExF) impairments, which contribute to the psychological and everyday burden of CHD. Cortical dysmaturation has been well described in fetuses and neonates with CHD and early evidence suggests that cortical alterations in thickness, surface area, and gyrification index are non-transient and can be observed in adolescents with CHD. However, cortical alterations have yet to be correlated with ExF deficits in youth with CHD. This study aims to use a data-driven approach to identify the most important cortical features associated with ExF deficits in adolescents and young adults with CHD. To do so, we combined two comparable datasets acquired at the Research Institute of the McGill University Health Centre and the University Children’s Hospital Zurich each including both youth with CHD and healthy controls. For each participant, a high-resolution T1-weighted magnetic resonance image, a self-reported ExF assessment (the Behaviour Rating Inventory of Executive Function— Adult Scale), and their clinical and demographic characteristics were available. Corticometric Iterative Vertex-Based Estimation of Thickness (CIVET) was used to extract cortical thickness, cortical surface area, and local gyrification index measures. Using orthogonal projective non-negative matrix factorization (OPNMF), we identified non-overlapping spatial components that integrate cortical thickness, cortical surface area, and local gyrification index and capture structural covariance across these features. Behavioural partial least squares correlation (bPLS) analysis was then used to compute correlations between the individual variability in the OPNMF covariance patterns and ExF outcomes for each subject. A total of 56 youth with CHD who underwent cardiopulmonary bypass surgery before three years of age and 56 age- and sex-matched healthy controls were included in our analyses. Cortical grey matter volume, cortical thickness, and cortical surface area were found to be significantly reduced in CHD patients compared to controls. OPNMF identified 12 stable cortex-wide components summarizing the inter-subject variability in cortical thickness, cortical surface area, and local gyrification index. bPLS revealed two significant latent variables (LV) accounting for a total of 82.8% of the variance in the sample, each describing distinct patterns between the brain and cognitive data. LV1 summarized a pattern of belonging to the CHD group, worse scores on most BRIEF-A scales, younger age at MRI, and female sex. This pattern was associated with increased cortical thickness, local gyrification index, and decreased cortical surface area in several OPNMF components. Finally, we identified a positive relationship between the LV1 brain-behaviour pattern and total aortic cross-clamp time in the CHD group, indicating that longer aortic cross-clamp time was associated with worse neurodevelopmental outcomes. In this study, we uncover novel multivariate relationships between ExF and alterations in cortical thickness, surface area, and local gyrification index in adolescents and young adults with CHD using a data-driven approach. Although our findings highlight the important role played by the cortex in higher order cognitive processes, future studies are needed to elucidate the individual contribution of individual and clinical attributes into the deficits observed in this population.

Compensatory mechanisms amidst demyelinating disorders: insights into cognitive preservation.

Demyelination disrupts the transmission of electrical signals in the brain and affects neurodevelopment in children with disorders such as multiple sclerosis and myelin oligodendrocyte glycoprotein-associated disorders. Although cognitive impairments are prevalent in these conditions, some children maintain cognitive function despite substantial structural injury. These findings raise an important question: in addition to the degenerative process, do compensatory neural mechanisms exist to mitigate the effects of myelin loss? We propose that a multi-dimensional approach integrating multiple neuroimaging modalities, including diffusion tensor imaging, magnetoencephalography and eye-tracking, is key to investigating this question. We examine the structural and functional connectivity of the default mode and executive control networks due to their significant roles in supporting higher-order cognitive processes. As cognitive proxies, we examine saccade reaction times and direction errors during an interleaved pro- (eye movement towards a target) and anti-saccade (eye movement away from a target) task. 28 typically developing children, 18 children with multiple sclerosis and 14 children with myelin oligodendrocyte glycoprotein-associated disorders between 5 and 18.9 years old were scanned at the Hospital for Sick Children. Tractography of diffusion MRI data examined structural connectivity. Intracellular and extracellular microstructural parameters were extracted using a white matter tract integrity model to provide specific inferences on myelin and axon structure. Magnetoencephalography scanning was conducted to examine functional connectivity. Within groups, participants had longer saccade reaction times and greater direction errors on the anti- versus pro-saccade task; there were no group differences on either task. Despite similar behavioural performance, children with demyelinating disorders had significant structural compromise and lower bilateral high gamma, higher left-hemisphere theta and higher right-hemisphere alpha synchrony relative to typically developing children. Children diagnosed with multiple sclerosis had greater structural compromise relative to children with myelin oligodendrocyte glycoprotein-associated disorders; there were no group differences in neural synchrony. For both patient groups, increased disease disability predicted greater structural compromise, which predicted longer saccade reaction times and greater direction errors on both tasks. Structural compromise also predicted increased functional connectivity, highlighting potential adaptive functional reorganisation in response to structural compromise. In turn, increased functional connectivity predicted faster saccade reaction times and fewer direction errors. These findings suggest that increased functional connectivity, indicated by increased alpha and theta synchrony, may be necessary to compensate for structural compromise and preserve cognitive abilities. Further understanding these compensatory neural mechanisms could pave the way for the development of targeted therapeutic interventions aimed at enhancing these mechanisms, ultimately improving cognitive outcomes for affected individuals.