Functional network dynamics in a neurodevelopmental disorder of known genetic origin.

Dynamic connectivity in functional brain networks is a fundamental aspect of cognitive development, but we have little understanding of the mechanisms driving variability in these networks. Genes are likely to influence the emergence of fast network connectivity via their regulation of neuronal processes, but novel methods to capture these rapid dynamics have rarely been used in genetic populations. The current study redressed this by investigating brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with a ZDHHC9-associated intellectual disability to individuals with no known impairment. We characterised transient network dynamics using a Hidden Markov Model (HMM) on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation. The HMM is a data-driven method that captures rapid patterns of coordinated brain activity recurring over time. Resting-state network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation and, crucially, ZDHHC9 gene expression levels predicted the group differences in dynamic connectivity across networks. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between regional gene expression and brain network dynamics, and present the new application of a powerful method for understanding the neural mechanisms linking genetic variation to cognitive difficulties

Gene functional networks and autism spectrum characteristics in young people with intellectual disability: a dimensional phenotyping study

Funder: Baily Thomas Charitable Fund; doi: http://dx.doi.org/10.13039/501100001262Abstract: Background: The relationships between specific genetic aetiology and phenotype in neurodevelopmental disorders are complex and hotly contested. Genes associated with intellectual disability (ID) can be grouped into networks according to gene function. This study explored whether individuals with ID show differences in autism spectrum characteristics (ASC), depending on the functional network membership of their rare, pathogenic de novo genetic variants. Methods: Children and young people with ID of known genetic origin were allocated to two broad functional network groups: synaptic physiology (n = 29) or chromatin regulation (n = 23). We applied principle components analysis to the Social Responsiveness Scale to map the structure of ASC in this population and identified three components—Inflexibility, Social Understanding and Social Motivation. We then used Akaike information criterion to test the best fitting models for predicting ASC components, including demographic factors (age, gender), non-ASC behavioural factors (global adaptive function, anxiety, hyperactivity, inattention), and gene functional networks. Results: We found that, when other factors are accounted for, the chromatin regulation group showed higher levels of Inflexibility. We also observed contrasting predictors of ASC within each network group. Within the chromatin regulation group, Social Understanding was associated with inattention, and Social Motivation was predicted by hyperactivity. Within the synaptic group, Social Understanding was associated with hyperactivity, and Social Motivation was linked to anxiety. Limitations: Functional network definitions were manually curated based on multiple sources of evidence, but a data-driven approach to classification may be more robust. Sample sizes for rare genetic diagnoses remain small, mitigated by our network-based approach to group comparisons. This is a cross-sectional study across a wide age range, and longitudinal data within focused age groups will be informative of developmental trajectories across network groups. Conclusion: We report that gene functional networks can predict Inflexibility, but not other ASC dimensions. Contrasting behavioural associations within each group suggest network-specific developmental pathways from genomic variation to autism. Simple classification of neurodevelopmental disorder genes as high risk or low risk for autism is unlikely to be valid or useful

Dataset for: Auditory White Noise Exposure Modulates Human Cortical Excitability Patterns

dataset for calculating excitability indice

Auditory white noise exposure results in intrinsic cortical excitability changes

Summary: Cortical excitability is commonly measured by applying magnetic stimulation in combination with measuring behavioral response. This measure has, however, some shortcomings including spatial limitation to the primary motor cortex and not accounting for intrinsic excitability fluctuations. Here, we use a measure for intrinsic excitability based on phase synchronization previously validated for epilepsy. We apply this measure in 30 healthy participants’ magnetoencephalography (MEG) recordings during the exposure of auditory white noise, a stimulus that has been suggested to modify cortical excitability. Using cortical parcellation of the MEG source data, we could find a specific pattern of increased and decreased excitability while participants are exposed to white noise vs. silence. Specifically, excitability during white noise exposure decreases in the frontal lobe and increases in the temporal lobe. This study thus adds to the understanding of cortical excitability changes due to specific environmental stimuli as well as the spatial extent of these effects

[Formula: see text]FarmApp: a new assessment of cognitive control and memory for children and young people with neurodevelopmental difficulties.

We introduce a new touchscreen-based method measuring aspects of cognitive control and memory, in children and young people with neurodevelopmental difficulties, including intellectual disability (ID). FarmApp is a gamified, tablet-based assessment tool measuring go/no-go response speed, response inhibition, visuospatial short-term memory span, and long-term memory. Here, we assessed the feasibility, validity, and utility of the method, including the benefits of measuring change in performance over two weeks. We observed that: 1) a higher proportion of participants completed FarmApp than traditional psychometric tests; 2) this proportion increased when participants had opportunity for two weeks of self-paced testing at home; 3) ADHD-relevant behavioral difficulties were associated with average go/no-go performance across all attempts, and change in go/no-go performance over time, indicating sensitivity of the method to cognitive differences with real-world relevance. We also addressed the potential utility of the FarmApp for exploring links between ID etiology and cognitive processes. We observed differences in go/no-go task between two groups of ID participants stratified by the physiological functions of associated genetic variants (chromatin-related and synaptic-related). Moreover, the synaptic group demonstrated higher degree of improvement in go/no-go performance over time. This outcome is potentially informative of dynamic mechanisms contributing to cognitive difficulties within this group. In sum, FarmApp is a feasible, valid, and useful tool increasing access to cognitive assessment for individuals with neurodevelopmental difficulties of variable severity, with an added opportunity to monitor variation in performance over time and determine capacity to acquire task competence

The importance of ROI extraction method for MEG connectivity estimation. Practical recommendations for the study of resting state functional connectivity.

The zipped file contains all the t-maps of the contrasts across extraction methods, ROIs, frequency bands. Maps relative to different connectivity measurements are grouped in folders. Each folder also contains the .gii file for the reference cortex surface. You may use several softwares to visualize these maps. If you wish to visualize the maps with Brainstorm: 1) Go to Default Anatomy. Right Click -> Import surface. Select Group_analysis_cortex.gii. 2) Go to the Group_analysis data folder (you should create one if not present). Go to Common Files. Right Click -> File -> Import Source Maps. Select the t-maps to be visualized. For any additional info, please get in touch with the corresponding author