The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

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.

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.

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.

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.

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.

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.

MEG Assessment of Expressive Language in Children Evaluated for Epilepsy Surgery.

Establishing language dominance is an important step in the presurgical evaluation of patients with refractory epilepsy. In the absence of a universally accepted gold-standard non-invasive method to determine language dominance in the preoperative assessment, a range of tools and methodologies have recently received attention. When applied to pediatric age, many of the proposed methods, such as functional magnetic resonance imaging (fMRI), may present some challenges due to the time-varying effects of epileptogenic lesions and of on-going seizures on maturational phenomena. Magnetoencephalography (MEG) has the advantage of being insensitive to the distortive effects of anatomical lesions on brain microvasculature and to differences in the metabolism or vascularization of the developing brain and also provides a less intimidating recording environment for younger children. In this study we investigated the reliability of lateralized synchronous cortical activation during a verb generation task in a group of 28 children (10 males and 18 females, mean age 12 years) with refractory epilepsy who were evaluated for epilepsy surgery. The verb generation task was associated with significant decreases in beta oscillatory power (13-30 Hz) in frontal and temporal lobes. The MEG data were compared with other available presurgical non-invasive data including cortical stimulation, neuropsychological and fMRI data on language lateralization where available. We found that the lateralization of MEG beta power reduction was concordant with language dominance determined by one or more different assessment methods (i.e. cortical stimulation mapping, neuropsychological, fMRI or post-operative data) in 89% of patients. Our data suggest that qualitative hemispheric differences in task-related changes of spectral power could offer a promising insight into the contribution of dominant and non-dominant hemispheres in language processing and may help to characterize the specialization and lateralization of language processes in children.

Meta-analysis of cognitive functioning in patients following kidney transplantation.

Background: There is mixed evidence regarding the nature of cognitive function in patients who have undergone renal transplantation. The aim of this meta-analysis was to examine which cognitive domains are impacted following kidney transplantation and how performance compares with non-transplanted patients or healthy controls/normative data. Method: A systematic search was conducted using keywords within three databases (Embase, MEDLINE and PsychINFO), yielding 458 unique studies, 10 of which met the inclusion criteria. Neuropsychological tests were grouped into nine cognitive domains and three separate analyses were undertaken within each domain: (i) within subjects pre- versus post-transplant, (ii) transplanted versus non-transplanted patients and (iii) transplanted versus healthy matched controls and standardized normative data. Results: Transplanted patients showed moderate to large improvements in the domains of general cognitive status (g = 0.526), information and motor speed (g = 0.558), spatial reasoning (g = 0.376), verbal memory (g = 0.759) and visual memory (g = 0.690) when compared with their pre-operative scores. Test scores in the same five domains were significantly better in post-transplanted patients when compared with dialysis-dependant or conservatively managed chronic kidney disease patients. However, post-transplanted patients' performance was significantly low compared with that of healthy controls (and standardized normative data) in the domains of executive functioning (g = -0.283), verbal fluency (g = -0.657) and language (g = -0.573). Conclusions: Two key issues arise from this review. First, domain-specific cognitive improvement occurs in patients after successful transplantation. Nevertheless, transplanted patients still performed significantly below healthy controls in some domains. Second, there are important shortcomings in existing studies; the length of follow-up is typically short and only limited neuropsychological test batteries are employed. These factors are important in order to support the recovery of cognitive function among patients following renal transplant.

A Neuropsychological Profile for Agenesis of the Corpus Callosum? Cognitive, Academic, Executive, Social, and Behavioral Functioning in School-Age Children.

OBJECTIVES: Agenesis of the corpus callosum (AgCC), characterized by developmental absence of the corpus callosum, is one of the most common congenital brain malformations. To date, there are limited data on the neuropsychological consequences of AgCC and factors that modulate different outcomes, especially in children. This study aimed to describe general intellectual, academic, executive, social and behavioral functioning in a cohort of school-aged children presenting for clinical services to a hospital and diagnosed with AgCC. The influences of age, social risk and neurological factors were examined. METHODS: Twenty-eight school-aged children (8 to 17 years) diagnosed with AgCC completed tests of general intelligence (IQ) and academic functioning. Executive, social and behavioral functioning in daily life, and social risk, were estimated from parent and teacher rated questionnaires. MRI findings reviewed by a pediatric neurologist confirmed diagnosis and identified brain characteristics. Clinical details including the presence of epilepsy and diagnosed genetic condition were obtained from medical records. RESULTS: In our cohort, ~50% of children experienced general intellectual, academic, executive, social and/or behavioral difficulties and ~20% were functioning at a level comparable to typically developing children. Social risk was important for understanding variability in neuropsychological outcomes. Brain anomalies and complete AgCC were associated with lower mathematics performance and poorer executive functioning. CONCLUSIONS: This is the first comprehensive report of general intellectual, academic, executive social and behavioral consequences of AgCC in school-aged children. The findings have important clinical implications, suggesting that support to families and targeted intervention could promote positive neuropsychological functioning in children with AgCC who come to clinical attention. (JINS, 2018, 24, 445-455).

Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy.

PURPOSE: The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well-characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. METHODS: Participants were 105 Australian children aged 6-8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS). RESULTS: Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores. SIGNIFICANCE: Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low-dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.

Perinatal psychiatric disorders: an overview.

Perinatal mental illness has a significant implication on maternal health, birth outcomes, and the offspring's development. Prevalence estimates of perinatal psychiatric illnesses range widely, with substantial heterogeneity in different population studies, with a lower prevalence rate in high- rather than low- or middle-income countries. Because of the potential negative impact on maternal and child outcomes and the potential lability of these disorders, the perinatal period is a critical time to identify psychiatric illnesses. Thus, obstetricians and midwives play a crucial role in assessing women's mental health needs and to refer identified women promptly for multidisciplinary specialist assessment. However, there is still limited evidence on best practice assessment and management policies during pregnancy and postpartum. This review focuses on the prevalence of common perinatal mental disorders and antenatal screening policies to identify women at risk. The effect of these conditions and their management on pregnancy, fetal outcomes, and child development are discussed.

Developmental stage affects cognition in children with recently-diagnosed symptomatic focal epilepsy.

This study explored the impact of developmental stage on cognitive function in children with recently-diagnosed epilepsy. In keeping with a neurodevelopmental framework, skills in a critical developmental period were expected to be more vulnerable than those stable at the time of seizure onset. We studied children with early-onset (EO) symptomatic focal epilepsy (onset: 3-5 years; n=18) and compared their performance with that of the group with late-onset (LO) epilepsy (onset: 6-8 years performance of; n=8) on a range of cognitive tasks. Performance of both groups was compared with normative standards. 'Critical' and 'stable' classifications were based on developmental research. Nonparametric analyses revealed that skills in a critical developmental period for the group with EO epilepsy fell below normative standards (Phonological Processing: p=.007, Design Copying: p=.01, Visuomotor Precision:, p=.02) and fell below the performance of the group with LO epilepsy (Design Copying: p=.03, Visuomotor Precision: p=.03). There were no differences between the group with EO epilepsy and the group with LO epilepsy on measures of receptive vocabulary and memory, which were proposed to be in a stable developmental period across both groups. Auditory span, as measured by Word Order, was reduced for both the group with EO epilepsy (p=.02) and the group with LO epilepsy (p=.02) relative to normative standards, but the groups did not differ from each other. These results are consistent with a prolonged period of critical development for this skill. These findings support the notion that skills in a critical phase of development are particularly vulnerable following the onset of symptomatic focal epilepsy in childhood.

Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex.

The neuropeptide oxytocin (OXT) plays an important role in complex socio-affective behaviours such as affiliation, attachment, stress and anxiety. Previous studies have focused on the amygdala as an important target of OXT's effects. However, the effects of OXT on connectivity of the amygdala with cortical regions such as medial frontal cortex, an important mediator of social cognition and emotion regulation, remain unexplored. In a randomized, double-blind, cross-over design, 15 volunteers received intranasal OXT or placebo prior to resting-state functional magnetic resonance imaging. OXT significantly increased connectivity between both amygdalae and rostral medial frontal cortex (rmFC), while having only negligible effects on coupling with other brain regions. These results demonstrate that OXT is a robust and highly selective enhancer of amygdala connectivity with rmFC, a region critical to social cognition and emotion regulation, and add to our understanding of the neural mechanisms by which OXT modulates complex social and cognitive behaviours.

Handedness and corpus callosal morphology in Williams syndrome.

Williams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

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.

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.

Stereotaxic localisation of the dorsolateral prefrontal cortex for transcranial magnetic stimulation is superior to the standard reference position.

OBJECTIVE: To determine whether the standard method of localisation of the dorsolateral prefrontal cortex for repetitive transcranial magnetic stimulation is accurate and reliable, and to develop an empirically based method for operational localisation of the dorsolateral prefrontal cortex with reference to the motor hand area. METHOD: We compared stereotaxic localisation of the dorsolateral prefrontal cortex with the commonly used operational definition of 6 cm anterior to the site of the abductor pollicis brevis muscle in healthy participants (n = 18). We also report the average translational distance from the site of the abductor pollicis brevis to the stereotaxically defined dorsolateral prefrontal cortex. RESULTS: The stereotaxic method was less variable than the operational method of localisation and more frequently targeted the middle frontal gyrus. The average translational distance from the site of the abductor pollicis brevis to the stereotaxically targeted dorsolateral prefrontal cortex was x = -5 mm, y = 53 mm and z = -31 mm. CONCLUSIONS: Operational localisation of the dorsolateral prefrontal cortex for repetitive transcranial magnetic stimulation with reference to the motor hand area is more variable than stereotaxic localisation. If future studies choose to use an operational definition of the left dorsolateral prefrontal cortex, we suggest it should be 5 mm lateral, 53 mm anterior and 31 mm inferior to the site of the abductor pollicis brevis.