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

Altered cortical thickness following prenatal sodium valproate exposure

Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA dose and right IFG thickness, and a close relationship between verbal skills and left IFG thickness. A significant interaction between group and hemispheric IFG thickness showed absence of the normal asymmetry in the IFG region of VPA-exposed children. These data provide preliminary insights into the putative neural basis of difficulties experienced by some VPA-exposed children

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the ‘social brain network’ (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2–8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems

Uncovering the neuroanatomical correlates of cognitive, affective and conative theory of mind in paediatric traumatic brain injury: a neural systems perspective

Deficits in theory of mind (ToM) are common after neurological insult acquired in the first and second decade of life, however the contribution of large-scale neural networks to ToM deficits in children with brain injury is unclear. Using paediatric traumatic brain injury (TBI) as a model, this study investigated the sub-acute effect of paediatric traumatic brain injury on grey-matter volume of three large-scale, domain-general brain networks (the Default Mode Network, DMN; the Central Executive Network, CEN; and the Salience Network, SN), as well as two domain-specific neural networks implicated in social-affective processes (the Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy Network, MNEN). We also evaluated prospective structure–function relationships between these large-scale neural networks and cognitive, affective and conative ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children [TBI: n = 103; typically developing (TD) children: n = 34]. All children were assessed on measures of ToM at 24-months post-injury. Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN, MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions of these neural networks. Volumetric reductions in the CCMN and several of its hub regions, including the cerebellum, predicted poorer cognitive ToM. In contrast, poorer affective and conative ToM were predicted by volumetric reductions in the SN and MNEN, respectively. Overall, results suggest that cognitive, affective and conative ToM may be prospectively predicted by individual differences in structure of different neural systems—the CCMN, SN and MNEN, respectively. The prospective relationship between cerebellar volume and cognitive ToM outcomes is a novel finding in our paediatric brain injury sample and suggests that the cerebellum may play a role in the neural networks important for ToM. These findings are discussed in relation to neurocognitive models of ToM. We conclude that detection of sub-acute volumetric abnormalities of large-scale neural networks and their hub regions may aid in the early identification of children at risk for chronic social-cognitive impairment

Community-based interventions for adolescents following traumatic brain injury: a systematic review

Background: Chronic impairment following childhood traumatic brain injury has the potential to increase risk of negative outcomes. This highlights potential value of community-based rehabilitation programs. Objectives: To identify research studies examining existing intervention programmes available in community-based rehabilitation to adolescents following TBI to assist with the transition back into the community. Methods: A systematic review of community-based interventions was conducted across different national contexts. All included studies involved a clinical population with TBI, aged 11 to 25 years inclusive. Risk of bias was rated for each included study. Results: Seventeen studies were identified for inclusion in the review, of these eleven distinct interventions were found. The quality of evidence was largely weak and highly variable. Conclusion: The results suggest some improvement in adolescent outcomes following community-based interventions, however higher quality evidence is needed to support specific interventions

A novel cognitive behavioural intervention with Theory of Mind (ToM) training for children with epilepsy: protocol for a case series feasibility study

Abstract Background Children with epilepsy have significant social impairments, yet evidence-based interventions to address these social difficulties are lacking. Emerging research has shown that social difficulties in children with epilepsy relate to underlying impairments in Theory of Mind (ToM). This paper outlines the protocol for a pilot study that will evaluate the feasibility, acceptability, and efficacy of a novel cognitive behavioural intervention with ToM training for children with epilepsy. Methods The intervention will be evaluated in a single-arm case series feasibility study. Ten to 12 children with common forms of epilepsy (8 to 12 years old) will be recruited to participate in 4 small group workshops, held over 4 consecutive weeks. Parents will attend a brief review at the end of each session with their child. Children will complete 4 one-to-one assessments with an investigator assessing ToM and social competence: twice at baseline (4 weeks and 1 day before the intervention), at post-intervention (last day of the intervention) and at follow-up (4 weeks post intervention). Parents will complete online questionnaires at these same 4 time points assessing ToM and social competence of their child. Parents and children will both complete a weekly measure of social competence from baseline 1 to follow-up. Following completion of the intervention, parents will complete two standardised questionnaires assessing treatment acceptability and barriers and facilitators to attendance; children will complete a single questionnaire on treatment acceptability. Information about feasibility outcomes (i.e. recruitment and retention, processing time, suitability of tasks) will be gathered by investigators during the trial. Together, outcomes will be used to refine research methods and make a decision about whether the intervention should be evaluated in a larger scale trial. Discussion To our knowledge, this is the first psychosocial intervention to address social competence problems in children with epilepsy. Findings will provide information about a potentially effective treatment that could improve longer term social outcomes for this group. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12618000974202, registered June 8 2018

Music therapy for early cognitive rehabilitation post childhood TBI: an intrinsic mixed methods case study

Objective: The primary aim of this case study was to explore the behavioural changes of a paediatric patient in post-traumatic amnesia (PTA) during a music therapy session. A secondary objective was to measure the effect of the music therapy intervention on agitation.Method: Video data from pre, during and post-music therapy sessions were collected and analysed using video micro-analysis and the Agitated Behaviour Scale.Results: The participant displayed four discrete categories of behaviours: Neutral, Acceptance, Recruitment and Rejection. Further analysis revealed brief but consistent and repeated periods of awareness and responsiveness to the live singing of familiar songs, which were classified as Islands of Awareness. Song offered an Environment of Potential to maximise these periods of emerging consciousness. The quantitative data analysis yielded inconclusive results in determining if music therapy was effective in reducing agitation during and immediately post the music therapy sessions. Conclusion: The process of micro-analysis illuminated four discrete participant behaviours not apparent in the immediate clinical setting. The results of this case suggest that the use of familiar song as a music therapy intervention may harness early patient responsiveness to foster cognitive rehabilitation in the early acute phase post-TBI