Language and communication functioning in children and adolescents with agenesis of the corpus callosum.

The corpus callosum, the largest white matter inter-hemispheric pathway, is involved in language and communication. In a cohort of 15 children and adolescents (8-15 years) with developmental absence of the corpus callosum (AgCC), this study aimed to describe language and everyday communication functioning, and explored the role of anatomical factors, social risk, and non-verbal IQ in these outcomes. Standardised measures of language and everyday communication functioning, intellectual ability and social risk were used. AgCC classification and anterior commissure volume, a potential alternative pathway, were extracted from T1-weighted images. Participants with AgCC showed reduced receptive and expressive language compared with test norms, and high rates of language and communication impairments. Complete AgCC, higher social risk and lower non-verbal IQ were associated with communication difficulties. Anterior commissure volume was not associated with language and communication. Recognising heterogeneity in language and communication functioning enhances our understanding and suggests specific focuses for potential interventions.

A digital intervention to support childhood cognition after the COVID-19 pandemic: a pilot trial.

Difficulties in executive functioning (EF) can result in impulsivity, forgetfulness, and inattention. Children living in remote/regional communities are particularly at risk of impairment in these cognitive skills due to reduced educational engagement and poorer access to interventions. This vulnerability has been exacerbated by the COVID-19 pandemic and strategies are needed to mitigate long-term negative impacts on EF. Here we propose a pilot trial investigating the benefits, feasibility, and acceptability of a school-based EF intervention for primary school students (6-8 years) living in regional, developmentally vulnerable, and socio-economically disadvantaged communities. Students were randomised to a digital intervention or teaching as usual, for 7 weeks. Children completed measures of EF and parents/educators completed ratings of everyday EF and social/emotional wellbeing at pre-intervention, post-intervention, and 3-month follow-up. Change in EFs (primary outcome), everyday EF, and social/emotional wellbeing (secondary outcomes) from pre- to post-intervention and pre-intervention to 3-month follow-up were examined. Feasibility and acceptability of the intervention was assessed through educator feedback and intervention adherence.Protocol Registration: The stage 1 protocol for this Registered Report was accepted in principle on 20 April 2023. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/WT3S2 . The approved Stage 1 protocol is available here: https://osf.io/kzfwn .

Exploring Working Memory Capacity and Efficiency Processes to Understand Working Memory Training Outcomes in Primary School Children.

Despite the abundance of research evaluating working memory training outcomes in children, few studies have examined the underlying cognitive mechanisms. This study aimed to contribute understanding by exploring whether working memory capacity (maximum span) and/or efficiency (basic and cognitive processing speeds), two proposed cognitive mechanisms, are associated with children's working memory performance immediately and 6-months post-intervention. We used data from a previous trial in primary school children (7-11 years) who completed working memory training (n = 52) or an active control (n = 36), comprising 10 sessions (each 20-minutes) in class over two weeks. Children completed five working memory measures at baseline, immediately and 6-months post-intervention: two Backwards Span and two Following Instructions measures (same paradigms as training activities), and one n-back measure (different paradigm). Maximum span, basic and cognitive processing speeds, and performance were calculated for each measure. Associations between change in maximum span, processing speeds and change in performance on the working memory measures from baseline to immediately and 6-months post-intervention did not differ between groups (all p < .05). Maximum span, processing speeds and performance on working memory measures did not differ between groups. Findings provide little evidence that the studied capacity or efficiency processes contribute to understanding working memory training outcomes in primary school children. Furthermore, working memory training did not have benefits for children's working capacity, efficiency or performance up to 6-months post-intervention. It is of interest for future studies to explore cognitive mechanisms, including strategy use, maximum span and information processing, in datasets where training effects are observed.

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.

Working Memory Training for Children Using the Adaptive, Self-Select, and Stepwise Approaches to Setting the Difficulty Level of Training Activities: Protocol for a Randomized Controlled Trial.

BACKGROUND: A common yet untested assumption of cognitive training in children is that activities should be adaptive, with difficulty adjusted to the individual's performance in order to maximize improvements on untrained tasks (known as transfer). Working memory training provides the ideal testbed to systematically examine this assumption as it is one of the most widely studied domains in the cognitive training literature, and is critical for children's learning, including following instructions and reasoning. OBJECTIVE: This trial aimed to examine children's outcomes of working memory training using adaptive, self-select (child selects difficulty level), and stepwise (difficulty level increases incrementally) approaches to setting the difficulty of training activities compared to an active control condition immediately and 6-month postintervention. While the aim is exploratory, we hypothesized that children allocated to a working memory training condition would show greater improvements: (1) on near transfer measures compared to intermediate and far transfer measures and (2) immediately postintervention compared to 6-month postintervention. METHODS: This double-blinded, active-controlled, parallel-group randomized trial aimed to recruit 128 children aged 7 to 11 years from 1 metropolitan primary school in Melbourne, Australia. Following baseline testing, children were randomized into 1 of 4 conditions: adaptive, self-select, or stepwise working memory training, or active control. An experimental intervention embedded in Minecraft was developed for teachers to deliver in class over 2 consecutive weeks (10 × 20-minute sessions). The working memory training comprised 2 training activities with processing demands similar to daily activities: backward span and following instructions. The control comprised creative activities. Pre- and postintervention, children completed a set of working memory tests (near and intermediate transfer) and the Raven's Standard Progressive Matrices (far transfer) to determine training outcomes, as well as motivation questionnaires to determine if motivations toward learning and the intervention were similar across conditions. Caregivers completed the ADHD-Rating Scale-5 to measure their child's attention (far transfer). Statistical analysis will include traditional null hypothesis significance testing and Bayesian methods to quantify evidence for both the null and alternative hypotheses. RESULTS: Data collection concluded in December 2022. Data are currently being processed and analyzed. CONCLUSIONS: This trial will determine whether the adaptive approach to setting the difficulty of training activities maximizes cognitive training outcomes for children. This trial has several strengths: it adopts best practices for cognitive training studies (design, methods, and analysis plan); uses a range of measures to detect discrete levels of transfer; has a 6-month postintervention assessment; is appropriately powered; and uses an experimental working memory training intervention based on our current understanding of the cognitive mechanisms of training. Findings will inform future research and design of cognitive training interventions and highlight the value of the evidence-based principles of cognitive training. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12621000990820; https://www.anzctr.org.au/ACTRN12621000990820.aspx. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47496.

Relationship Between Parental Postnatal Distress and 5-Year Mental Health Outcomes of Children Born at <30 Weeks and at Term.

OBJECTIVE: The purpose of this study was to compare mental health symptoms and diagnoses at age 5 years between children born <30 weeks' gestation and their term-born peers and associations with postnatal symptoms of depression and anxiety in their mothers and fathers. METHODS: Parents of children born <30 weeks' gestation (n = 106) and at term (n = 105) completed measures of anxiety and depression symptoms within 4 weeks of birth and questionnaires assessing child socioemotional symptoms and mental health/neurodevelopmental diagnostic criteria at age 5 years. RESULTS: At age 5 years, children born <30 weeks' gestation were more likely to show clinically concerning levels of total difficulties (odds ratio [OR] = 3.97, 95% confidence interval [CI], 1.21-13.05), emotional problems (OR = 3.71, 95% CI, 1.14-12.15), and inattention/hyperactivity problems (OR = 4.34, 95% CI, 1.51-12.47) than term-born peers. They also showed higher rates of mental health/neurodevelopmental diagnoses than their term-born peers (18% vs 9%), although evidence for the group difference was weak ( p = 0.08). Maternal postnatal anxiety and depression symptoms were related to poorer child mental health outcomes in many domains. There was little evidence that paternal postnatal anxiety/depression symptoms were related to child outcomes or that any associations varied by birth group. CONCLUSION: Children born <30 weeks' gestation showed more mental health symptoms than their term-born peers at age 5 years. Maternal postnatal distress was associated with poorer child mental health across both groups, reinforcing the need for early identification and support of mental health distress in the postnatal period to improve longer-term child well-being.

Against the use of the Strengths and Difficulties Questionnaire for Aboriginal and Torres Strait Islander children aged 2-15 years.

OBJECTIVE: The Strengths and Difficulties Questionnaire is a widely used screening tool for emotional and behavioural problems in children. Recent quantitative analyses have raised concerns regarding its structural validity in Aboriginal and Torres Strait Islander communities. This paper aims to extend upon existing findings by analysing the factor structure of both the parent- and teacher-reported Strengths and Difficulties Questionnaire in this population across a broader age range than in previous studies. METHODS: Participants were the caregivers and teachers of 1624 Aboriginal and Torres Strait Islander children (820 male, 804 female) aged 2-15 years from Waves 2-11 of the Longitudinal Study of Indigenous Children. The majority of children were Aboriginal living in major cities and inner regional areas. Internal consistency was estimated with McDonald's Omega. Exploratory structural equation modelling was conducted to investigate the factor structure of the parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire. RESULTS: Responses from teachers demonstrated higher internal consistency than responses from parents, which was unacceptably low across most age groups. The purported five-factor structure of the Strengths and Difficulties Questionnaire failed to be replicated across both parent- and teacher-reported questionnaires. The results of bifactor and hierarchical exploratory structural equation models also failed to approximate the higher-order summary scales. These results indicate that the Strengths and Difficulties Questionnaire subscales and summary scores do not provide a valid index of emotional and behavioural problems in Aboriginal and Torres Strait Islander children. CONCLUSION: The Strengths and Difficulties Questionnaire should not be used with Aboriginal and Torres Strait Islander children.

Parental Mental Health and Parenting Behaviors Following Very Preterm Birth: Associations in Mothers and Fathers and Implications for Child Cognitive Outcome.

OBJECTIVES: To investigate the longitudinal associations between parental mental health symptoms within 4 weeks of birth, parenting behaviors at 1 year, and child general cognitive ability at 4.5-5 years in a sample of children born very preterm (VP). This study also examined whether these associations differed based on level of family social risk. METHODS: Participants were 143 children born <30 weeks' gestation and their parents. Within 4 weeks of birth, mothers' and fathers' depressive and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and Hospital Anxiety Depression Scale-Anxiety Subscale. Parents' sensitive and structuring parenting behaviors were assessed at 1 year using the Emotional Availability Scales. Child general cognitive ability was assessed at 4.5-5 years using the Wechsler Preschool & Primary Scale of Intelligence-Fourth Edition. RESULTS: Higher maternal depressive symptoms were associated with lower levels of sensitive and structuring parenting behavior, while higher maternal anxiety symptoms were associated with higher levels of structuring parenting behavior. There was weak evidence for positive associations between mothers' sensitive parenting behavior and fathers' structuring parenting behavior and child general cognitive ability. There was also weak evidence for stronger associations between mothers' mental health symptoms, parenting behaviors, and child general cognitive ability, in families of higher compared with lower social risk. CONCLUSIONS: Depressive and anxiety symptoms experienced by mothers in the initial weeks following VP birth can have long-term effects on their parenting behaviors. Enquiring about parents' mental health during their child's hospitalization in the neonatal intensive care unit is crucial.

Episodic and prospective memory difficulties in 13-year-old children born very preterm.

OBJECTIVES: Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years. METHOD: VP (n = 81: born <30 weeks' gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life. RESULTS: The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP. CONCLUSIONS: Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.

Can Neurocognitive Outcomes Assist Measurement-Based Care for Children with Attention-Deficit/Hyperactivity Disorder? A Systematic Review and Meta-Analyses of the Relationships Among the Changes in Neurocognitive Functions and Clinical Outcomes of Attention-Deficit/Hyperactivity Disorder in Pharmacological and Cognitive Training Interventions.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental conditions among school-age children. Early intervention and ongoing evaluation of treatment effectiveness are essential to minimize the life-long negative impact of ADHD. Neurocognitive functions have been reported to improve with pharmacological and cognitive training interventions for children with ADHD. We evaluated the value of measuring change in neurocognitive functions following ADHD interventions as a treatment outcome. We systematically reviewed randomized control trials of two distinctive types of ADHD interventions-pharmacological treatments and cognitive training-and summarized the changes in neurocognitive and clinical outcomes using a series of meta-analyses. Both pharmacological and cognitive training interventions showed positive effects on some aspects of neurocognitive functions. However, there were no significant correlations between changes in neurocognitive function (e.g., inhibition) and changes in ADHD behavioral symptoms (e.g., impulsive behavior). Although the associations between changes in neurocognitive function and clinical outcomes are not well studied, based on current findings, it is not suitable to use change in neurocognitive outcomes as a proxy for change in ADHD clinical symptom-based outcomes. There is, however, notable value in monitoring changes in neurocognitive function associated with ADHD interventions to achieve the following aims: (1) understanding full treatment effect on children with ADHD, (2) identifying ancillary indicators of subclinical changes, and (3) provision of objective and less biased measures of treatment effects. These findings are important evidence that changes in neurocognitive function could be a co-occurring objective indication that parallels the clinical effects of ADHD treatments.

Thirteen-Year Outcomes of a Randomized Clinical Trial of Early Preventive Care for Very Preterm Infants and Their Parents.

OBJECTIVE: To evaluate 13-year outcomes of a randomized controlled trial of preventive care (VIBeS Plus) for infants born very preterm and their parents and examine whether possible effects of intervention varied by family social risk. STUDY DESIGN: Families were randomized to an intervention arm (n = 61) or a standard care arm (n = 59). The intervention was delivered at home by psychologists and physiotherapists over the infants' first year, focusing on infant development and parental mental health. At 13 years corrected age, cognitive, motor, and behavioral outcomes, and parental mental health were assessed. Primary estimands were between-group mean differences, estimated using multiple imputed regression models. RESULTS: Follow-up included 81 surviving children (69%). There was little evidence of benefits of the intervention for IQ, attention, executive functioning, working memory, and academic skills regardless of level of social risk. Specifically, mean differences in adolescent cognitive outcomes ranged from -2.0 units (95% CI, -9.9 to 5.9) in favor of standard treatment to 5.1 units (95% CI, -2.3 to 12.5) favoring the intervention. A group-by-social risk interaction was observed only for adolescent motor outcomes, with mean differences favoring the intervention for those at higher social risk (balance, 4.9; 95% CI, 1.3-8.5; total motor, 3.2; 95% CI, 0.3-6.2), but not those at lower social risk (balance, -0.3; 95% CI, -2.4 to 1.9; total motor, 0.03; 95% CI, -1.9 to 2.0). Mean differences in adolescent behavior and parental mental health ranged from -6.6 (95% CI -13.8, 0.5) to -0.2 (95% CI, -1.9 to 1.4) and -1.8 (95% CI, -4.1 to 0.6) to -1.7 (95% CI, -4.3 to 1.0), respectively, indicating a pattern of fewer symptoms in the intervention group. CONCLUSIONS: Benefits of the intervention persisted for adolescent behavior, with better motor outcomes observed in those from socially disadvantaged families. Replication with larger samples, multiple informant reports, and assessment of quality of life-related outcomes is warranted. TRIAL REGISTRATION: http://www.anzctr.org.au/: ACTRN12605000492651.

Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the T 1-w/T 2-w Ratio.

BACKGROUND AND OBJECTIVES: To investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of T 1- and T 2-weighted MRI (T 1-w/T 2-w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years. METHODS: Prospective longitudinal cohort study of VP (born <30 weeks' gestation or <1,250 g) and FT infants born between 2001 and 2004 and followed up at term equivalent and 7 and 13 years of age, including MRI studies and neurodevelopmental assessments. T 1-w/T 2-w images were parcellated into 48 white matter regions of interest. RESULTS: Of 224 VP participants and 76 FT participants, 197 VP and 55 FT participants had useable T 1-w/T 2-w data from at least one timepoint. T 1-w/T 2-w values increased between term equivalent and 13 years of age, with little evidence that longitudinal changes varied between birth groups or sexes. VP birth, neonatal brain abnormalities, being small for gestational age, and postnatal infection were associated with reduced regional T 1-w/T 2-w values in childhood and adolescence. Increased T 1-w/T 2-w values across the white matter at 13 years were associated with better motor and working memory function for all children. Within the FT group only, larger increases in T 1-w/T 2-w values from term equivalent to 7 years were associated with poorer attention and executive function, and higher T 1-w/T 2-w values at 7 years were associated with poorer mathematics performance. DISCUSSION: VP birth and multiple known perinatal risk factors are associated with long-term reductions in the T 1-w/T 2-w ratio in white matter regions in childhood and adolescence, which may relate to alterations in microstructure and myelin content. Increased T 1-w/T 2-w ratio at 13 years appeared to be associated with better motor and working memory function and there appeared to be developmental differences between VP and FT children in the associations for attention, executive functioning, and mathematics performance.

Maternal Mental Health Disorders Following Very Preterm Birth at 5 Years Post-Birth.

OBJECTIVE: Mothers of children born very preterm (VP) are at increased risk of developing postnatal depression, anxiety, and post-traumatic stress symptoms. However, mental health disorder rates are rarely assessed in this population compared with full-term peers, and it is unclear if postnatal distress symptoms precede higher rates of maternal mental health disorders at 5 years post-birth in both birth groups. METHODS: Mothers of children born VP (n = 65; mean [SD] age at birth, 33.9 [5.0]; 72.1% tertiary educated) and full-term (n = 90; mean [SD] age at birth, 33.4 [4.0]; 88.2% tertiary educated) completed questionnaires assessing symptoms of depression, anxiety, and trauma within 4 weeks of birth. At 5 years post-birth, they participated in a structured diagnostic interview assessing mood, anxiety, and trauma-related mental health disorders, both current and over the lifetime. RESULTS: There was little evidence for differences between mothers in the VP and full-term groups in rates of any mental health disorder at 5 years (VP = 14%, full-term = 14%) or lifetime (VP = 41%, full-term = 37%). In mothers of children born VP, elevated postnatal post-traumatic stress symptoms were associated with higher rates of mental health disorders at 5 years (odds ratio = 21.5, 95% confidence interval = 1.35-342). CONCLUSIONS: Findings suggest that preterm birth may not lead to increased odds of later developing maternal mental health disorders, despite known risks of elevated postnatal distress following a VP birth. However, those with post-traumatic stress symptoms following a VP birth could be more vulnerable, and assessment and monitoring is recommended.

Parenting and Neurobehavioral Outcomes in Children Born Moderate-to-Late Preterm and at Term.

OBJECTIVES: To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2 years of corrected age between children born moderate-to-late preterm (MLP; 32-36 weeks of gestation) and at term (≥37 weeks of gestation). STUDY DESIGN: Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers' parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2 years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social-emotional competence using the Infant Toddler Social and Emotional Assessment. RESULTS: Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference -0.32 [-0.60, -0.04]; P = .03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P < .001 MLP; P = .02 term), increased maternal structuring was associated with better social-emotional competence (P = .02 MLP; P = .03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P < .04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. CONCLUSIONS: Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.

Oculomotor deficits in attention deficit hyperactivity disorder (ADHD): A systematic review and comprehensive meta-analysis.

Atypical motor coordination and cognitive processes, such as response inhibition and working memory, have been extensively researched in individuals with attention deficit hyperactivity disorder (ADHD). Oculomotor neural circuits overlap extensively with regions involved in motor planning and cognition, therefore studies of oculomotor function may offer unique insights into motor and cognitive control in ADHD. We performed a series of pairwise meta-analyses based on data from 26 oculomotor studies in ADHD to examine whether there were differences in performance on visually-guided saccade, gap, antisaccade, memory-guided, pursuit eye movements and fixation tasks. These analyses revealed oculomotor disturbances in ADHD, particularly for difficulties relating to saccade inhibition, memorizing visual target locations and initiating antisaccades. There was no evidence for pursuit eye movement disturbances or saccade dysmetria. Investigating oculomotor abnormalities in ADHD may provide insight into top-down cognitive control processes and motor control, and may serve as a promising biomarker in ADHD research and clinical practice.

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.

A neural index of inefficient evidence accumulation in dyslexia underlying slow perceptual decision making.

Visual processing deficits have been widely reported in developmental dyslexia however the locus of cognitive dysfunction remains unclear. Here, we examined the neural correlates of perceptual decision-making using a dot-motion task and electroencephalography (EEG) and investigated whether presenting deficits were unique to children with dyslexia or if they were also evident in other, typically developing children with equally immature reading systems. Sixty-eight children participated: 32 with dyslexia (DD; 16 females); 21 age-matched controls (AM; 11 females) and 15 reading-matched controls (RM; 9 females). All participants completed a bilaterally presented random-dot-motion task while EEG was recorded. Neural signatures of low level sensory processing (steady state visual evoked potentials; SSVEPs), pre-target attentional bias (posterior α power), attentional orienting (N2), evidence accumulation (centro-parietal positive decision signal; CPP) and execution of a motor response (ß) were obtained to dissect the temporal sequence of perceptual decision-making. Reading profile provided a score of relative lexical and sublexical skills for each participant. Although all groups performed comparably in terms of task accuracy and false alarm rate, the DD group were slower and demonstrated an earlier peak latency, reduced slope and lower amplitude of the CPP compared with both AM and RM controls. Reading profile was found to moderate the relationship between word reading ability, reaction time as well as CPP indices showing that lexical dyslexics responded more slowly and had a shallower slope, reduced amplitude and earlier latency of CPP waveforms than sublexical dyslexics. These findings suggest that children with dyslexia, particularly those with relatively poorer lexical abilities, have a reduced rate and peak of evidence accumulation as denoted by CPP markers yet remain slow in their overt response. This is in keeping with hypotheses that children with dyslexia have impairment in effectively sampling and processing evidence about visual motion stimuli.

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.