NeuroImage: Reports

Introduction Language functional MRI (fMRI) is a valuable tool for presurgical planning in epilepsy. Functional MRI can be challenging in children, and head motion can compromise its utility. The candidacy of patients with ADHD for fMRI is sometimes queried regarding concerns about possible head motion. In 2020, we implemented an fMRI task training program, via telehealth and/or mock MRI. We aimed to determine whether training increased language lateralisation success and/or reduced head motion in all patients, and in those with ADHD. We also aimed to determine whether patients with ADHD exhibited more head motion during fMRI than those without ADHD. Methods We retrospectively identified 223 epilepsy (85%) and other neurosurgery patients, (241 scans including repeats) with language fMRI at Royal Children's Hospital, Melbourne, Australia, 2016-2024. There were 24 individuals with ADHD listed in the Electronic Medical Record, five of whom had diagnoses of both ADHD and autism; and nine with autism. Language lateralisation success was determined by clinician description recorded as left/right/bilateral in the medical record. 99 patients were provided the training including fMRI task practise. Head motion was quantified by maximum Framewise Displacement (FDmax; mm). Results ADHD was associated with lower language lateralisation success. Training was associated with greater language lateralisation success, across all patients, and in those with ADHD. Regarding ADHD and head motion, outliers in FDmax were seen in 5 young patients with ADHD. Data were trimmed to allow separate investigation of FDmax for the sample with and without extremes of head motion. In untrimmed data, FDmax was significantly higher in patients with ADHD than in those without. In trimmed data, FDmax was on average lower in patients with ADHD than those without, however this was not statistically supported. Regarding training and head motion, across all patients, FDmax was significantly lower for scans with training than without. In patients with ADHD, FDmax was on average lower for scans with training, however training was not associated with FDmax. Conclusions Language fMRI training was associated with higher language lateralization success, particularly in patients with ADHD. Training was associated with reduced head motion across all patients. Although some young patients with ADHD had substantial head motion, most in our sample did not move more than those without ADHD. We conclude that the training program increases success of language fMRI, and that an ADHD diagnosis should not be a contraindication to language fMRI.

Very preterm (VPT) young adolescents are at high risk of executive, behavioural and socio-emotional difficulties. Previous research has shown significant evidence of the benefits of mindfulness-based intervention (MBI) on these abilities. This study aims to assess the association between the effects of MBI on neurobehavioral functioning and changes in white-matter microstructure in VPT young adolescents who completed an 8-week MBI program. Neurobehavioural assessments and multi-shell diffusion MRI were performed before and after MBI in 32 VPT young adolescents. Combined diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) measures were extracted on well-defined white matter tracts (TractSeg). A multivariate data-driven approach (partial least squares correlation) was used to explore associations between MBI-related changes on neurobehavioural measures and microstructural changes. Our finding showed an enhancement of global executive functioning after MBI that was associated with a general pattern of significant increase in fractional anisotropy (FA) and decrease in axonal dispersion (ODI) in white-matter tracts involved in executive processes. Young VPT adolescents with lower gestational age at birth showed the greatest gain in white-matter microstructural changes after MBI. HighlightsO_LIVery preterm adolescents (VPT) completed an 8-week mindfulness-based intervention (MBI) C_LIO_LIImprovement in overall executive functioning was observed after MBI C_LIO_LIExecutive gain was associate with white-matter microstructural changes C_LIO_LIThe increase in microstructural properties was in tracts involved in executive processes C_LIO_LIVPT with lower gestational age show bigger gains in microstructural changes C_LI CRediT rolesVanessa Siffredi: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Software; Visualization; Writing - original draft; Writing - review & editing - Maria Chiara Liverani: Conceptualization; Data curation; Investigation; Methodology; Project administration; Writing - review & editing. - Dimitri Van De Ville: Methodology; Resources; Software; Supervision; Writing - review & editing. - Lorena Freitas: Data curation; Investigation; Writing - review & editing. - Cristina Borradori Tolsa: Conceptualization; Funding acquisition; Investigation; Project administration; Resources; Supervision; Validation; Writing - review & editing. - Petra Susan Huppi: Conceptualization; Funding acquisition; Methodology; Project administration; Resources; Supervision; Validation; Writing - review & editing. -Russia Ha-Vinh Leuchter: Conceptualization; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Writing - review & editing.

Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.

The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.

BackgroundThe Cambridge Centre for Ageing and Neuroscience (Cam-CAN) started in 2010 to study the effect of healthy adult ageing on cognition and the brain in a population-derived sample. The study design and protocol for Phases 1-3 of Cam-CAN were detailed in Shafto et al. (2014); this paper outlines the design and protocol of Phases 4-5, which enable longitudinal investigation of cognitive and brain ageing over approximately 12 years. More details about the Cam-CAN project can be found here: www.cam-can.org. Methods/DesignPhase 4 was an at-home assessment of cognition, demographics and lifestyle, performed approximately 6 years after Phase 1 (baseline assessment), for which all people from Phase 1 were invited. Phase 5 combined repeated online cognitive, demographics and lifestyle assessment, followed by in-lab attendance for MRI and MEG brain scanning, approximately 12 years after Phase 1, for which all people from Phase 2 (baseline brain assessment) were invited. Demographics, lifestyle and cognitive data are therefore now available for three timepoints, and MRI and MEG brain data for two timepoints. DiscussionThe Cam-CAN study offers deep and wide phenotyping of neurocognitive health across the adult lifespan (18-96). These rich data will allow researchers to address questions like: why do some people maintain their cognitive abilities better than others, in terms of their brain structure or function, their lifestyle and/or their genetics? Given the shifting demographics towards old age in most countries, this knowledge will be important to help people function independently for longer, reducing both individual and societal burden.

IntroductionSustained attention and inhibition processes are fundamental components of attention that mature during adolescence, a transitive period between childhood and adulthood characterized by a rapid behavioral and cognitive development. The current study aimed to provide a better understanding of sustained attention and inhibition processes in typically developing adolescents (n = 26) aged 11-18. MethodsFunctional magnetic resonance images (fMRI) were acquired during two different modalities (the face and the scene) from a previously validated gradual{square}onset continuous (gradCPT) paradigm to evaluate sustained attention performances. In addition, we performed linear regression analyses to investigate how cerebral activation varied as a function of covariates of interest. ResultsWe showed a bilateral fronto-parieto-occipito brain activation during response inhibition regardless the type of task. Participants demonstrated better behavioral performances during the scene gradCPT. We observed a mainly left-lateralized pattern of activation in a fronto-cingulo-cerebellum area during the face gradCPT and an extended bilateral fronto-temporo-parieto-occipital activation during the scene gradCPT. Finally, we found associations between brain activity and behavioral attentional responses. ConclusionThis study gives a better understanding of the neural correlates of sustained attention and inhibition in a typically developing adolescent population.

Children born very preterm (VPT; < 32 completed weeks of gestation) are at high risk of neurodevelopmental and neurobehavioral difficulties associated with atypical brain maturation. The analysis of large-scale brain network dynamics during rest allows to investigate brain functional connectivity and their association with behavioural outcomes. Of interest, prematurity has been associated with atypical socio-emotional development with significant implications for the forming of peer relationships, adaptive functioning, academic achievement and mental health. In this study, we extracted dynamic functional connectivity by using the innovation-driven co-activation patterns (iCAPs) framework in preterm and full-term children aged 6 to 9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity. Multivariate pattern analysis was used to explore potential biomarkers for socio-emotional difficulties in preterm children. Results show a spatial organisation of 13 networks retrieved comparable to full-term controls. Dynamic features and lateralisation of network brain activity were also comparable across groups for all large-scale brain networks. Despite apparent similarities in terms of dynamical functional connectivity parameters, multivariate pattern analysis unveiled group differences in their associations with socio-emotional abilities. While a pattern of decreased engagement in certain brain networks were associated with better socio-emotional abilities in full-term controls; in the VPT group, better socio-emotional abilities were associated with coordination of activity across different networks, i.e., coupling duration between different pairs of networks. It is possible that group differences reflect reduced degree of maturation of functional architecture in the VPT group for socio-emotional abilities.

This multimodal brain imaging study investigated functional MRI (fMRI) neural processing of cardiac interoceptive signals in 38 patients with functional neurological disorder (FND) compared to 38 healthy controls (HCs). Additionally, we characterized how brain fMRI responses during heartbeat counting (interoception) vs. tone counting (exteroception) or rest related to grey matter volume, interoceptive awareness, and psychopathology scores. For both interoception vs. rest and interoception vs. exteroception contrasts, principal component analyses showed that principal component 1 (PC1) as derived from all study participants was comprised primarily of salience, ventral attention and sensorimotor network co-activations, along with default mode and visual processing network co-deactivations. Compared to HCs, patients with FND showed reduced contribution to these PC1 co-activation/co-deactivations patterns in both interoception vs. exteroception and interoception vs. rest contrasts; only the interoception vs. exteroception between-group fMRI findings held adjusting for depression/anxiety scores, antidepressant use and FND subtype. For the interoception vs. rest contrast, increasingly negative PC1 contribution scores positively correlated with decreased cingulate gyrus volumes and increased psychopathology scores. This multimodal brain imaging study underscores a role for salience and default-mode networks in the pathophysiology of FND, and sets the stage for comprehensive research efforts further contextualizing the mechanistic importance of altered interoception in patients with FND.

A cardinal feature of the encephalopathy of prematurity is dysmaturation of developing white matter and subsequent hypomyelination. Magnetisation transfer imaging (MTI) offers surrogate markers for myelination including magnetisation transfer ratio (MTR) and magnetisation transfer saturation (MTsat). Using data from 105 neonates, we characterise MTR and MTsat in the developing brain and investigate how these markers are affected by gestational age at scan and preterm birth. We explore correlations of the two measures with fractional anisotropy (FA), radial diffusivity (RD) and T1w/T2w ratio which are commonly used markers of white matter integrity in early life. We used two complementary analysis methods: voxel-wise analysis across the white matter skeleton, and tract-of-interest analysis across 16 major white matter tracts. We found that MTR and MTsat positively correlate with gestational age at scan. Preterm infants at term-equivalent age had lower values of MTsat in the genu and splenium of the corpus callosum, while MTR was higher in central white matter regions, the corticospinal tract and the uncinate fasciculus. Correlations of MTI metrics with other MRI parameters revealed that there were moderate positive correlations between T1w/T2w and MTsat and MTR at voxel-level, but at tract-level FA had stronger positive correlations with these metrics. RD had the strongest correlations with MTI metrics, particularly with MTsat in major white matter tracts. The observed changes in MTI metrics are consistent with an increase in myelin density during early postnatal life, and lower myelination and cellular/axonal density in preterm infants at term-equivalent age compared to term controls. Furthermore, correlations between MTI-derived features and conventional measures from dMRI provide new understanding about the contribution of myelination to non-specific imaging metrics that are often used to characterise early brain development.

Concurrent transcranial direct current stimulation (tDCS) and proton Magnetic Resonance Spectroscopy (1H MRS) experiments have shown up- or downregulation of neurotransmitter concentration. However, effects have been modest applying mostly lower current doses and not all studies found significant effects. Dose of stimulation might be an important variable in eliciting a consistent response. To investigate dose effects of tDCS on neurometabolites, we placed an electrode over the left supraorbital region (with a return electrode over the right mastoid bone) and utilized an MRS voxel (3x3x3cm) that was centered over the anterior cingulate/inferior mesial prefrontal region which is in the path of the current distribution. We conducted 5 epochs of acquisition, each one with a 9:18min acquisition time, and applied tDCS in the third epoch. We observed significant dose and polarity dependent modulation of GABA and to a lesser degree of Glutamine/Glutamate (GLX) with the highest and reliable changes seen with the highest current dose, 5mA (current density 0.39 mA/cm2), during and after the stimulation epoch compared with pre-stimulation baselines. The strong effect on GABA concentration (achieving a mean change of 63% from baseline, more than twice as much as reported with lower doses of stimulation) establishes tDCS-dose as an important parameter in eliciting a regional brain engagement and response. Furthermore, our experimental design in examining tDCS parameters and effects using shorter epochs of acquisitions might constitute a framework to explore the tDCS parameter space further and establish measures of regional engagement by non-invasive brain-stimulation.

AIMChildren born preterm (PT) experience perinatal white matter injury and later reading deficits at school age. We used two complementary neuroimaging modalities to determine if reading skills would be associated with contemporaneous white matter properties in school-aged PT children. METHODIn 8-year-old PT children (N=29), we measured diffusivity (fractional anisotropy, FA), from diffusion MRI, and myelin content (relaxation rate, R1) from quantitative relaxometry. We assessed reading (Grays Oral Reading Test, Fifth Edition) in each child. Whole-brain deterministic tractography coupled with automatic segmentation and quantification were applied to extract FA and R1 along four tracts and assess their statistical association with reading scores. RESULTSReading-FA correlations were not significant along the four analyzed tracts. Reading-R1 correlations were significantly positive in portions of the left superior longitudinal fasciculus, right uncinate fasciculus, and left inferior longitudinal fasciculus. FA positively correlated with R1 in limited areas of reading-R1 associations, but did not contribute to the variance in reading scores. INTERPRETATIONCombining complementary neuroimaging approaches identified relations between reading and white matter properties not found using a single MRI measure. Associations of reading skills and white matter properties may vary across white matter tracts and metrics in PT children. What this paper adds{blacksquare} Preterm childrens reading was associated with white matter myelin content. {blacksquare}Preterm childrens reading was not associated with white matter diffusivity.

Transcranial direct current stimulation (tDCS) over the prefrontal cortex has the potential to enhance working memory by means of a weak direct current applied to the scalp. However, its effects are highly variable and possibly dependent on individual variability in cortical architecture and head anatomy. Unveiling sources of heterogeneity might improve fundamental and clinical application of tDCS in the field. Therefore, we investigated sources of tDCS variability of prefrontal 1.5mA tDCS, 3mA tDCS and sham tDCS in 40 participants (67.5% women, mean age 24.7 years) by associating simulated electric field (E-field) magnitude in brain regions of interest (dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and subgenual ACC) and working memory performance. Emotional and non-emotional 3-back paradigms were used. In the tDCS protocol analysis, effects were only significant for the 3mA group, and only for the emotional tasks. In the individual E-field magnitude analysis, faster responses in non-emotional, but not in the emotional task, were associated with stronger E-fields in all brain regions of interest. A follow-up analysis showed that people with higher (vs. lower) E-fields magnitude in the left DLPFC were faster in the both tasks, and more accurate in the emotional task. Concluding, individual E-field distribution might explain part of the variability of prefrontal tDCS effects on working memory performance and in clinical samples. Our results suggest that tDCS effects can be more consistent or improved by applying personalizing current intensity, although this hypothesis should be confirmed by further studies.

BackgroundThe left inferior frontal gyrus (IFG) has been shown to be involved in sentence comprehension in many studies through its involvement in both semantic and syntactic computations. However, causal evidence for its involvement in sentence comprehension is scarce. We used transcranial direct current stimulation (tDCS) to test the causal involvement of the left IFG in sentence comprehension in a group of individuals with primary progressive aphasia (PPA). These individuals participated in a tDCS study targeting lexical retrieval only, not sentence comprehension, therefore in the present study we report on far-transfer effects of tDCS in sentence comprehension. ObjectiveWe sought to determine whether tDCS over the left inferior frontal gyrus (IFG) coupled with lexical retrieval treatment may improve sentence comprehension in PPA. MethodWithin a sham-controlled, double-blind design, we tested whether 15 daily sessions of anodal tDCS over the left IFG may improve sentence comprehension in 27 people with PPA, and whether the tDCS effects were sustained up to two months post-treatment. ResultsWe found that immediately post-treatment, and up to 2-months post-treatment, there was significantly larger improvement of sentence comprehension in the tDCS condition compared to sham. There were, however, differential effects of tDCS in each PPA variant and sentence-type. Importantly, participants with the epicenter of atrophy over the stimulated area (non-fluent PPA) benefited most from tDCS. ConclusionTDCS over the left IFG induces far-transfer effects and may improve sentence comprehension in PPA. We provide causal evidence that left IFG is a critical area for sentence comprehension.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSFragile X syndrome (FXS) is the most prevalent form of inherited intellectual disability and is the most common monogenetic cause of autism. Previous studies have linked the structural and functional alterations in FXS with impaired sensory processing and sensory hypersensitivity, which may hinder the early development of cognitive functions such as language comprehension. In this study, we compared the P1 response in event-related potential (ERP) and its habituation to repeated auditory stimuli in male children (2-7 years old) with and without FXS, and examined their association with clinical measures in these two groups. MethodsWe collected high-density electroencephalography (EEG) data in an auditory oddball paradigm from 12 children with FXS and 11 age- and sex-matched typically developing (TD) children. After standardized EEG pre-processing, we conducted a spatial principal component (PC) analysis and identified two major PCs -- a frontal PC and a temporal PC. Within each PC, we compared the P1 amplitude and inter-trial phase coherence (ITPC) between the two groups, and performed a series of linear regression analysis to study the association between these EEG measures and several clinical measures, including assessment scores for language development, non-verbal skills, and sensory hypersensitivity. ResultsAt the temporal PC, both early and late standard stimuli evoked a larger P1 response (p = 0.0037, p<0.0001, respectively) and higher ITPC (p = 0.0402, p = 0.0027) in FXS than in TD. We observed habituation of ITPC in both groups at the frontal PC (p = 0.0149 for FXS; p = 0.0244 for TD). Linear regression analysis showed that within the FXS group reduced frontal P1 response to late standard stimuli and increased habituation were associated with better languages scores. No associations were observed with non-verbal skills or sensory hypersensitivity. ConclusionWe identified P1 amplitude and ITPC in the temporal region as a contrasting EEG phenotype between the FXS and the TD groups. P1 response and habituation in the frontal region may be reflective of the language outcome in male children with FXS. These EEG measures are potential biomarkers for early diagnosis and future language development in patients with FXS.

ObjectiveThe aim of this pilot study was to assess associations of prenatal alcohol exposure (PAE), prenatal tobacco exposure (PTE), and their interaction and quantity on subsequent cortical and subcortical measures at age 6 years. MethodsMothers with varying levels of alcohol and tobacco exposure at different trimesters during pregnancy were approached when their children (born participating in the Safe Passage Study) were approximately 6 years old. 72 mothers agreed to participate, and 51 children completed brain magnetic resonance imaging (MRI). Brain regions of interest (ROIs) that were significantly associated prior to multiple comparison testing, were examined for associations related to exposure quantity, frequency, and timing (QFT), to explore how patterns of PAE and PTE influence brain outcomes in children. Linear regression was used to identify associations between PAE, PTE, and their interaction with cortical (n = 68 ROIs) and subcortical (n = 40 ROIs) measures. ResultsPrior to correction for multiple comparison testing, both PAE and PTE, as well as their interaction, were associated with a range of cortical and subcortical measures. However, none of these findings survived correction for multiple comparisons. Nevertheless, when exploring quantity of PAE, the total amount of standard drinks consumed during pregnancy and the average number of drinks per drinking day were positively associated with cortical volume in the right fusiform gyrus. ConclusionThese trend results in this pilot study provide preliminary evidence that PAE impacts brain development in unique ways from PTE, and their interactive co-exposure is not a straight forward synergistic or additive effect on the brain.

Identifying early biomarkers of restricted and repetitive behaviours among children with neurodevelopmental disorders may support the development of targeted therapeutic interventions in both clinical and educational settings, ultimately improving their learning experiences and long-term developmental trajectories. The objectives of the study were to examine midbrain dopamine and norepinephrine integrity in children with and without neurodevelopmental disorders using neuromelanin-sensitive magnetic resonance imaging, and the association with restricted and repetitive behaviours. Participants were enrolled in the Child and Adolescent Brain Imaging Network (CABIN) or the Fetal Imaging and Neurodevelopment (FIND) studies. All participants completed MRI and behavioural assessments, including parent-reported RRBs measured with the Repetitive Behavior Scale-Revised. A total of 88 infants, children and adolescents (mean [SD] age, 9.47 [5.41] years; 46 males) were included. Age positively predicted neuromelanin-MRI signal intensity in the substantia nigra ({beta}=.75, p<.001) and locus coeruleus ({beta}=.38, p=0.007). Further, locus-coeruleus neuromelanin-MRI signal intensity was significantly higher in children with ASD and ADHD compared to TD peers (both, p<.007). Among children with autism, lower signal predicted more severe self-injurious behaviours ({beta}=-.420, p=.006) and restricted interests ({beta}=-.629, p<.001). Findings indicate a role for neuromelanin concentration in the locus coeruleus as a candidate biomarker for restricted and repetitive behaviours, particularly in children with autism. These behaviours may reflect reduced noradrenergic signalling and impaired capacity for arousal regulation and behavioural control in children with lower LC neuromelanin signal. Findings highlight the importance of targeting the noradrenergic system when developing therapeutic strategies. Pharmacological interventions aimed at modulating the noradrenergic system and school-based strategies supporting arousal regulation, behavioural flexibility, and cognitive control may help reduce symptom severity and improve functioning.

Background: Transcranial direct current stimulation (tDCS) is increasingly used as an adjunct to rehabilitation for young people with cerebral palsy (CP), yet considerable variability exists in clinical response. Individualised electric field modelling provides an opportunity to estimate the distribution of electrical fields generated by the stimulation delivered to the brain and explore potential relationships with functional outcomes. Methods: Structural MRI scans from nineteen participants (10-16 years) from a previously published randomised controlled trial (ISRCTN74235136) investigating the effects of tDCS combined with motor training, underwent participant-specific finite element modelling using SimNIBS. Electric field strength was quantified within anatomically defined motor regions of interest, including the primary motor cortex (M1), dorsal premotor cortex (PMd), supplementary motor area (SMA), and a combined motor network. Global grey matter electric field metrics and stimulation focality were also extracted. Results: Estimated electric field strength differed significantly across motor regions (p<0.001), with PMd receiving significantly greater stimulation than both M1 and SMA. Electric field strength within a control region (primary visual cortex) was significantly lower than within M1 (p<0.001). Despite inter-individual variability in regional and global electric field metrics, no significant associations were observed between estimated electric field strength or focality and changes in function following intervention. Conclusion: Individualised electric field modelling demonstrated that an M1-targeted tDCS montage preferentially stimulated PMd rather than M1 in young people with CP. These findings highlight the importance of subject-specific modelling when characterising current distribution and suggest that variability in electric field strength alone does not explain variability in behavioural response.

BackgroundUnderstanding the neurobiology behind Fragile X syndrome (FXS) is critical in identifying effective therapeutics and improving care for affected individuals. Electroencephalography (EEG) provides an opportunity to investigate the biological foundations of this disorder. We aimed to characterize the visual evoked potential (VEP) in young children with FXS, and to understand how measures of the VEP are associated with verbal and nonverbal development within FXS. MethodsVEPs were collected in children between 2-7 years old with FXS (n = 9) as well as corresponding age-(n = 10) and cognitive-matched (n = 9) typically developing children. Additionally, the Mullen Scales of Early Learning and Preschool Language Scales were administered to collect measures of verbal and nonverbal development. Differences in component amplitudes and latencies of the VEP were assessed using ANCOVAs, and associations of VEP measures and verbal and nonverbal development were evaluated using linear regression with age as a covariate. ResultsNo differences between groups were observed in N1, P1, or N2 VEP components. However, a consistent and prominent P2 component (latency = 177ms {+/-} 13.7), was observed in children with FXS. The P2 amplitude was significantly increased in FXS children compared to the cognitive-matched group (p = 0.004). For children with FXS, the amplitude of several VEP components were associated with verbal and nonverbal development; larger N1 amplitude and smaller P1 and P2 amplitudes were all associated with better receptive language (all p<0.05) and larger N1 amplitude was also associated with better fine motor skills (p<0.05). ConclusionsThe observed increase in P2 amplitude and its negative association with language development within the FXS group supports the P2 component as a potential biomarker for FXS as a disorder, as well as a pathophysiological marker of verbal impairment that could be used in clinical trials.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience as difficulty understanding speech in background noise despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional, but not global, functional brain topology in children with APD. However, little is known about the brain structural organization in APD. We used diffusion MRI data to investigate the structural white matter connectome of 58 children from 8 to 14 years old diagnosed with APD (n=29) and children without hearing complaints (healthy controls, HC; n=29). We investigated the rich-club organization and structural connection differences between APD and HC groups using the network science approach. The APD group showed neither edge-based connectivity differences nor any differences in rich-club organization and connectivity strength (i.e., rich, feeder, local connections) compared to HCs. However, at the regional network level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in children with APD. HCs demonstrated a positive association between APL in the left orbital gyrus and the listening-in-spatialized-noise-sentences task, a measure of auditory processing ability. This correlation was not observed in the APD group. In line with previous functional connectome findings, the current results provide evidence for altered structural networks at a regional level in children with APD, and an association with listening performance, suggesting the involvement of multimodal deficits and a role for structure-function alteration in listening difficulties of children with APD.

Family history is one the most powerful risk factor for attention-deficit/hyperactivity disorder (ADHD), yet no study has tested whether multimodal Magnetic Resonance Imaging (MRI) combined with deep learning can separate familial ADHD (ADHD-F) and non-familial ADHD (ADHD-NF). T1-weighted and diffusion-weighted MRI data from 438 children (129 ADHD-F, 159 ADHD-NF, and 150 controls) were parcellated into 425 cortical and white-matter metrics. Our pipeline combined three feature-selection steps (t-test filtering, mutual-information ranking, and Lasso) with an auto-encoder and applied the binary-hypothesis strategy throughout; each held-out subject was assigned both possible labels in turn and evaluated under leave-one-out testing nested within five-fold cross-validation. Accuracy, sensitivity, specificity, and area under the curve (AUC) quantified performance. The model achieved accuracies/AUCs of 0.66 / 0.67 for ADHD-F vs controls, 0.67 / 0.70 for ADHD-NF vs controls, and 0.62 / 0.67 for ADHD-F vs ADHD-NF. In classification between ADHD-F and controls, the most informative metrics were the mean diffusivity (MD) of the right fornix, the MD of the left parahippocampal cingulum, and the cortical thickness of the right inferior parietal cortex. In classification between ADHD-NF and controls, the key contributors were the fractional anisotropy (FA) of the left inferior fronto-occipital fasciculus, the MD of the right fornix, and the cortical thickness of the right medial orbitofrontal cortex. In classification between ADHD-F and ADHD-NF, the highlighted features were the volume of the left cingulate cingulum tract, the volume of the right parietal segment of the superior longitudinal fasciculus, and the cortical thickness of the right fusiform cortex. Our binary hypothesis semi-supervised deep learning framework reliably separates familial and non-familial ADHD and shows that advanced semi-supervised deep learning techniques can deliver robust, generalizable neurobiological markers for neurodevelopmental disorders.