Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children.

OBJECTIVES: The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC). METHODS: Participants were 27 children with AgCC and 32 TD children 8-16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure. RESULTS: The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC. CONCLUSIONS: This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.

Predicting 'Brainage' in late childhood to adolescence (6-17yrs) using structural MRI, morphometric similarity, and machine learning.

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy children to predict an individual's age from structural MRI. This data-driven, predicted 'Brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this Brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel Brainage approaches using morphometric similarity against more typical, single feature (i.e., cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a Brainage framework, morphometric similarity does not provide more accurate predictions of age. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy participants in this way.

Predicting 'Brainage' in the Developmental Period using Structural MRI, Morphometric Similarity, and Machine Learning.

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy-children to predict an individual's age from structural MRI. This data-driven, 'brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel brain-age approaches using morphometric similarity against more typical, single feature (i.e. cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a brain-age framework, morphometric similarity does not explain more variance than individual structural features. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy individuals.

The development of the gut microbiome and temperament during infancy and early childhood: A systematic review.

Temperament in early childhood is a good predictor of later personality, behavior, and risk of psychopathology. Variation in temperament can be explained by environmental and biological factors. One biological mechanism of interest is the gut microbiome (GM), which has been associated with mental and physical health. This review synthesized existing literature evaluating the relationship between GM composition and diversity, and temperament in early life. Web of Science, PsycInfo, PubMed, and Scopus were searched, and data were extracted according to PRISMA guidelines. In total, 1562 studies were identified, of which six remained following application of exclusion/inclusion criteria. The findings suggest that there is an association between higher alpha diversity and temperament: greater Surgency/Extraversion and High-Intensity Pleasure in males, and lower Effortful Control in females. Unique community structures (beta diversity) were found for Surgency/Extraversion in males and Fear in females. An emerging pattern of positive temperament traits being associated with GM communities biased toward short-chain fatty acid production from a metabolism based on dietary fiber and complex carbohydrates was observed and is worthy of further investigation. To gain deeper understanding of the relationship, future research should investigate further the functional aspects of the microbiome and the influence of diet.

Frailty Is Associated With Cognitive Decline Independent of Cerebral Small Vessel Disease and Brain Atrophy.

BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time ß -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.

Parent and child mental health trajectories April 2020 to May 2021: Strict lockdown versus no lockdown in Australia.

OBJECTIVE: To control a second-wave COVID-19 outbreak, the state of Victoria in Australia experienced one of the world's first long and strict lockdowns over July-October 2020, while the rest of Australia experienced 'COVID-normal' with minimal restrictions. We (1) investigate trajectories of parent/child mental health outcomes in Victoria vs non-Victoria and (2) identify baseline demographic, individual and COVID-19-related factors associated with mental health trajectories. METHODS: Online community sample of 2004 Australian parents with rapid repeated assessment over 14 time-points over April 2020 to May 2021. Measures assessed parent mental health (Depression, Anxiety and Stress Scales-21), child depression symptoms (13-item Short Mood and Feelings Questionnaire) and child anxiety symptoms (four items from Brief Spence Children's Anxiety Scale). RESULTS: Mental health trajectories shadowed COVID-19 infection rates. Victorians reported a peak in mental health symptoms at the time of the second-wave lockdown compared to other states. Key baseline predictors, including parent and child loneliness (standardized regression coefficient [ß] = 0.09-0.46), parent/child diagnoses (ß = 0.07-0.21), couple conflict (ß = 0.07-0.18) and COVID-19 stressors, such as worry/concern about COVID-19, illness and loss of job (ß = 0.12-0.15), predicted elevated trajectories. Effects of predictors on parent and child mental health trajectories are illustrated in an online interactive app for readers (https://lingtax.shinyapps.io/CPAS_trend/). CONCLUSION: Our findings provide evidence of worse trajectories of parent and child mental health symptoms at a time coinciding with a second COVID-19 outbreak involving strict lockdown in Victoria, compared to non-locked states in Australia. We identified several baseline factors that may be useful in detecting high-risk families who are likely to require additional support early on in future lockdowns.

Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia.

OBJECTIVE: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Parents of 213 Australian children (5-17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). RESULTS: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3-0.6), less outdoor time (OR = 0.4; 95% 0.3-0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0-10.4), while television (OR = 4.0; 95% CI 2.5-6.5), social media (OR = 2.4; 95% CI 1.3-4.5), gaming (OR = 2.0; 95% CI 1.3-3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2-2.8), and loneliness (OR = 3.6; 95% CI 2.3-5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. CONCLUSIONS: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.

Structural-covariance networks identify topology-based cortical-thickness changes in children with persistent executive function impairments after traumatic brain injury.

Paediatric traumatic brain injury (pTBI) results in inconsistent changes to regional morphometry of the brain across studies. Structural-covariance networks represent the degree to which the morphology (typically cortical-thickness) of cortical-regions co-varies with other regions, driven by both biological and developmental factors. Understanding how heterogeneous regional changes may influence wider cortical network organization may more appropriately capture prognostic information in terms of long term outcome following a pTBI. The current study aimed to investigate the relationships between cortical organisation as measured by structural-covariance, and long-term cognitive impairment following pTBI. T1-weighted magnetic resonance imaging (MRI) from n = 83 pTBI patients and 33 typically developing controls underwent 3D-tissue segmentation using Freesurfer to estimate cortical-thickness across 68 cortical ROIs. Structural-covariance between regions was estimated using Pearson's correlations between cortical-thickness measures across 68 regions-of-interest (ROIs), generating a group-level 68 × 68 adjacency matrix for patients and controls. We grouped a subset of patients who underwent executive function testing at 2-years post-injury using a neuropsychological impairment (NPI) rule, defining impaired- and non-impaired subgroups. Despite finding no significant reductions in regional cortical-thickness between the control and pTBI groups, we found specific reductions in graph-level strength of the structural covariance graph only between controls and the pTBI group with executive function (EF) impairment. Node-level differences in strength for this group were primarily found in frontal regions. We also investigated whether the top n nodes in terms of effect-size of cortical-thickness reductions were nodes that had significantly greater strength in the typically developing brain than n randomly selected regions. We found that acute cortical-thickness reductions post-pTBI are loaded onto regions typically high in structural covariance. This association was found in those patients with persistent EF impairment at 2-years post-injury, but not in those for whom these abilities were spared. This study posits that the topography of post-injury cortical-thickness reductions in regions that are central to the typical structural-covariance topology of the brain, can explain which patients have poor EF at follow-up.

Large-scale functional network dynamics in human callosal agenesis: Increased subcortical involvement and preserved laterality.

In the human brain, the corpus callosum is the major white-matter commissural tract enabling the transmission of sensory-motor, and higher level cognitive information between homotopic regions of the two cerebral hemispheres. Despite developmental absence (i.e., agenesis) of the corpus callosum (AgCC), functional connectivity is preserved, including interhemispheric connectivity. Subcortical structures have been hypothesised to provide alternative pathways to enable this preservation. To test this hypothesis, we used functional Magnetic Resonance Imaging (fMRI) recordings in children with AgCC and typically developing children, and a time-resolved approach to retrieve temporal characteristics of whole-brain functional networks. We observed an increased engagement of the cerebellum and amygdala/hippocampus networks in children with AgCC compared to typically developing children. There was little evidence that laterality of activation networks was affected in AgCC. Our findings support the hypothesis that subcortical structures play an essential role in the functional reconfiguration of the brain in the absence of a corpus callosum.

Revisiting brain rewiring and plasticity in children born without corpus callosum.

The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split-brain patients, for whom the corpus callosum is surgically severed. Tovar-Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white-matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed.

Intra- and inter-hemispheric structural connectome in agenesis of the corpus callosum.

Agenesis of the corpus callosum (AgCC) is a congenital brain malformation characterized by the complete or partial failure to develop the corpus callosum. Despite missing the largest white matter bundle connecting the left and right hemispheres of the brain, studies have shown preserved inter-hemispheric communication in individuals with AgCC. It is likely that plasticity provides mechanisms for the brain to adjust in the context of AgCC, as the malformation disrupts programmed developmental brain processes very early on. A proposed candidate for neuroplastic response in individuals with AgCC is strengthening of intra-hemispheric structural connections. In the present study, we explore this hypothesis using a graph-based approach of the structural connectome, which enables intra- and inter-hemispheric analyses at multiple resolutions and quantification of structural characteristics through graph metrics. Structural graph metrics of 19 children with AgCC (13 with complete, 6 with partial AgCC) were compared to those of 29 typically developing controls (TDC). Associations between structural graph metrics and a wide range of neurobehavioral outcomes were examined using a multivariate data-driven approach (Partial Least Squares Correlation, PLSC). Our results provide new evidence suggesting structural strengthening of intra-hemispheric pathways as a neuroplastic response in the acallosal brain, and highlight regional variability in structural connectivity in children with AgCC compared to TDC. There was little evidence that structural graph properties in children with AgCC were associated with neurobehavioral outcomes. To our knowledge, this is the first report leveraging graph theory tools to explicitly characterize whole-brain intra- and inter-hemispheric structural connectivity in AgCC, opening avenues for future research on neuroplastic responses in AgCC.

Child and Parent Physical Activity, Sleep, and Screen Time During COVID-19 and Associations With Mental Health: Implications for Future Psycho-Cardiological Disease?

The COVID-19 pandemic has afforded the opportunity for some to improve lifestyle behaviours, while for others it has presented key challenges. Adverse changes in global lifestyle behaviours, including physical activity, sleep, and screen time can affect proximal mental health and in turn distal cardiovascular outcomes. We investigated differences in physical activity, sleep, and screen time in parents and children during early stages of the COVID-19 pandemic in Australia compared to pre-COVID-19 national data; and estimated associations between these movement behaviours with parent and child mental health. Cross-sectional baseline data from the COVID-19 Pandemic Adjustment Study (CPAS; N = 2,365) were compared to nationally representative pre-pandemic data from the Longitudinal Study of Australian Children (LSAC; N = 9,438). Participants were parents of children aged ≤ 18 years, residing in Australia. Parents provided self-report measures of mental health, physical activity and sleep quality, and reported on child mental health, physical activity and screen time. Children in CPAS had significantly more sleep problems and more weekend screen time. Their parents had significantly poorer sleep quality, despite increased weekly physical activity. Children's sleep problems were significantly associated with increased mental health problems, after accounting for socioeconomic status, physical activity, and screen time. Poorer parent sleep quality and lower levels of physical activity were significantly associated with poorer mental health. Monitoring this cohort over time will be important to examine whether changes in movement behaviour are enduring or naturally improve with the easing of restrictions; and whether these changes have lasting effects on either parent or child mental health, and in turn, future risk for CVD.

Structural Neuroplastic Responses Preserve Functional Connectivity and Neurobehavioural Outcomes in Children Born Without Corpus Callosum.

The corpus callosum is the largest white matter pathway in the brain connecting the two hemispheres. In the context of developmental absence (agenesis) of the corpus callosum (AgCC), a proposed candidate for neuroplastic response is strengthening of intrahemispheric pathways. To test this hypothesis, we assessed structural and functional connectivity in a uniquely large cohort of children with AgCC (n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioral outcomes using a multivariate data-driven approach (partial least squares correlation, PLSC). For structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in interhemispheric connectivity compared with TDC, in line with the aforementioned hypothesis. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intrahemispheric and interhemispheric connectivity. In conclusion, we observed structural strengthening of intrahemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioral outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.

Study Protocol for the COVID-19 Pandemic Adjustment Survey (CPAS): A Longitudinal Study of Australian Parents of a Child 0-18 Years.

BACKGROUND: The COVID-19 pandemic presents significant risks to the mental health and wellbeing of Australian families. Employment and economic uncertainty, chronic stress, anxiety, and social isolation are likely to have negative impacts on parent mental health, couple and family relationships, as well as child health and development. OBJECTIVE: This study aims to: (1) provide timely information on the mental health impacts of the emerging COVID-19 crisis in a close to representative sample of Australian parents and children (0-18 years), (2) identify adults and families most at risk of poor mental health outcomes, and (3) identify factors to target through clinical and public health intervention to reduce risk. Specifically, this study will investigate the extent to which the COVID-19 pandemic is associated with increased risk for parents' mental health, lower well-being, loneliness, and alcohol use; parent-parent and parent-child relationships (both verbal and physical); and child and adolescent mental health problems. METHODS: The study aims to recruit a close to representative sample of at least 2,000 adults aged 18 years and over living in Australia who are parents of a child 0-4 years (early childhood, N = 400), 5-12 years (primary school N = 800), and 13-18 years (secondary school, N = 800). The design will be a longitudinal cohort study using an online recruitment methodology. Participants will be invited to complete an online baseline self-report survey (20 min) followed by a series of shorter online surveys (10 min) scheduled every 2 weeks for the duration of the COVID-19 pandemic (i.e., estimated to be 14 surveys over 6 months). RESULTS: The study will employ post stratification weights to address differences between the final sample and the national population in geographic communities across Australia. Associations will be analyzed using multilevel modeling with time-variant and time-invariant predictors of change in trajectory over the testing period. CONCLUSIONS: This study will provide timely information on the mental health impacts of the COVID-19 crisis on parents and children in Australia; identify communities, parents, families, and children most at risk of poor outcomes; and identify potential factors to address in clinical and public health interventions to reduce risk.

Mapping language networks and their association with verbal abilities in paediatric epilepsy using MEG and graph analysis.

Recent theoretical models of language have emphasised the importance of integration within distributed networks during language processing. This is particularly relevant to young patients with epilepsy, as the topology of the functional network and its dynamics may be altered by the disease, resulting in reorganisation of functional language networks. Thus, understanding connectivity within the language network in patients with epilepsy could provide valuable insights into healthy and pathological brain function, particularly when combined with clinical correlates. The objective of this study was to investigate interactions within the language network in a paediatric population of epilepsy patients using measures of MEG phase synchronisation and graph-theoretical analysis, and to examine their association with language abilities. Task dependent increases in connectivity were observed in fronto-temporal networks during verb generation across a group of 22 paediatric patients (9 males and 13 females; mean age 14 years). Differences in network connectivity were observed between patients with typical and atypical language representation and between patients with good and poor language abilities. In addition, node centrality in left frontal and temporal regions was significantly associated with language abilities, where patients with good language abilities had significantly higher node centrality within inferior frontal and superior temporal regions of the left hemisphere, compared to patients with poor language abilities. Our study is one of the first to apply task-based measures of MEG network synchronisation in paediatric epilepsy, and we propose that these measures of functional connectivity and node centrality could be used as tools to identify critical regions of the language network prior to epilepsy surgery.

Clinically feasible brain morphometric similarity network construction approaches with restricted magnetic resonance imaging acquisitions.

Morphometric similarity networks (MSNs) estimate organization of the cortex as a biologically meaningful set of similarities between anatomical features at the macro- and microstructural level, derived from multiple structural MRI (sMRI) sequences. These networks are clinically relevant, predicting 40% variance in IQ. However, the sequences required (T1w, T2w, DWI) to produce these networks are longer acquisitions, less feasible in some populations. Thus, estimating MSNs using features from T1w sMRI is attractive to clinical and developmental neuroscience. We studied whether reduced-feature approaches approximate the original MSN model as a potential tool to investigate brain structure. In a large, homogenous dataset of healthy young adults (from the Human Connectome Project, HCP), we extended previous investigations of reduced-feature MSNs by comparing not only T1w-derived networks, but also additional MSNs generated with fewer MR sequences, to their full acquisition counterparts. We produce MSNs that are highly similar at the edge level to those generated with multimodal imaging; however, the nodal topology of the networks differed. These networks had limited predictive validity of generalized cognitive ability. Overall, when multimodal imaging is not available or appropriate, T1w-restricted MSN construction is feasible, provides an appropriate estimate of the MSN, and could be a useful approach to examine outcomes in future studies.

Developmental divergence of structural brain networks as an indicator of future cognitive impairments in childhood brain injury: Executive functions.

Brain insults during childhood can perturb the already non-linear trajectory of typical brain maturation. The diffuse effects of injury can be modelled using structural covariance networks (SCN), which change as a function of neurodevelopment. However, SCNs are estimated at the group-level, limiting applicability to predicting individual-subject outcomes. This study aimed to measure the divergence of the brain networks in paediatric traumatic brain injury (pTBI) patients and controls, and investigate relationships with executive functioning (EF) at 24 months post-injury. T1-weighted MRI acquired acutely in 78 child survivors of pTBI and 33 controls underwent 3D-tissue segmentation to estimate cortical thickness (CT) across 68 atlas-based regions-of-interest (ROIs). Using an 'add-one-patient' approach, we estimate a developmental divergence index (DDI). Our approach adopts a novel analytic framework in which age-appropriate reference networks to calculate the DDI were generated from control participants from the ABIDE dataset using a sliding-window approach. Divergence from the age-appropriate SCN was related to reduced EF performance and an increase in behaviours related to executive dysfunctions. The DDI measure showed predictive value with regard to executive functions, highlighting that early imaging can assist in prognosis for cognition.

Lesion Induced Error on Automated Measures of Brain Volume: Data From a Pediatric Traumatic Brain Injury Cohort.

Structural segmentation of T1-weighted (T1w) MRI has shown morphometric differences, both compared to controls and longitudinally, following a traumatic brain injury (TBI). While many patients with TBI present with abnormalities on structural MRI images, most neuroimaging software packages have not been systematically evaluated for accuracy in the presence of these pathology-related MRI abnormalities. The current study aimed to assess whether acute MRI lesions (MRI acquired 7-71 days post-injury) cause error in the estimates of brain volume produced by the semi-automated segmentation tool, Freesurfer. More specifically, to investigate whether this error was global, the presence of lesion-induced error in the contralesional hemisphere, where no abnormal signal was present, was measured. A dataset of 176 simulated lesion cases was generated using actual lesions from 16 pediatric TBI (pTBI) cases recruited from the emergency department and 11 typically-developing controls. Simulated lesion cases were compared to the "ground truth" of the non-lesion control-case T1w images. Using linear mixed-effects models, results showed that hemispheric measures of cortex volume were significantly lower in the contralesional-hemisphere compared to the ground truth. Interestingly, however, cortex volume (and cerebral white matter volume) were not significantly different in the lesioned hemisphere. However, percent volume difference (PVD) between the simulated lesion and ground truth showed that the magnitude of difference of cortex volume in the contralesional-hemisphere (mean PVD = 0.37%) was significantly smaller than that in the lesioned hemisphere (mean PVD = 0.47%), suggesting a small, but systematic lesion-induced error. Lesion characteristics that could explain variance in the PVD for each hemisphere were investigated. Taken together, these results suggest that the lesion-induced error caused by simulated lesions was not focal, but globally distributed. Previous post-processing approaches to adjust for lesions in structural analyses address the focal region where the lesion was located however, our results suggest that focal correction approaches are insufficient for the global error in morphometric measures of the injured brain.

Neurodevelopmental outcomes in paediatric immune-mediated and autoimmune epileptic encephalopathy.

Recognition of paediatric autoimmune/immune-mediated encephalitis and epileptic encephalopathy (e.g. NMDAR-Ab encephalitis) has rapidly increased over the last ten years. While we are succeeding in the diagnosis and identification and even early treatment of these encephalitidies, with studies describing >80% are making a "good" recovery, we are now recognising that a "good" medical outcome does not cover the cognitive, social and behavioural sequelae that can occur, particularly in paediatric patients. Basic measures of medical outcome, for example the modified Rankin Scale (MRS) or the Paediatric Cerebral Performance Category (PCPC), offer the advantage of being quick to use, but do not reveal the more complex difficulties that can impact the future of affected children. This article reviews the current literature on neurodevelopmental outcomes in children affected with autoimmune and immune-mediated encephalitis/epileptic encephalopathy and provides guidance on post-onset surveillance aimed at identifying those most likely to experience ongoing long-term difficulties.

Establishing a Developmentally Appropriate fMRI Paradigm Relevant to Presurgical Mapping of Memory in Children.

Functional magnetic resonance imaging (fMRI) is an established eloquent cortex mapping technique that is now an integral part of the pre-operative work-up in candidates for epilepsy surgery. Emerging evidence in adults with epilepsy suggests that material-specific fMRI paradigms can predict postoperative memory outcomes, however these paradigms are not suitable for children. In pediatric age, the use of memory fMRI paradigms designed for adults is complicated by the effect of developmental stages in cognitive maturation, the impairment experienced by some people with temporal lobe epilepsy (TLE) and the normal representation of memory function during development, which may differ from adults. We present a memory fMRI paradigm designed to activate mesial temporal lobe structures that is brief, independent of reading ability, and therefore a novel candidate for use in children. Data from 33 adults and 19 children (all healthy controls) show that the paradigm captures the expected leftward asymmetry of mesial temporal activation in adults. A more symmetrical pattern was observed in children, consistent with the progressive emergence of hemispheric specialisation across childhood. These data have important implications for the interpretation of presurgical memory fMRI in the pediatric setting. They also highlight the need to carefully consider the impact of cognitive development on fMRI tools used in clinical practice.