Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome. METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2). RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013). INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy.

AIM: To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. METHOD: Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography. RESULTS: More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. INTERPRETATION: Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls. WHAT THIS PAPER ADDS: Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.

Effect of Longitudinal Practice in Real and Virtual Environments on Motor Performance, Physical Activity and Enjoyment in People with Autism Spectrum Disorder: A Prospective Randomized Crossover Controlled Trial.

(1) Background: People with ASD commonly present difficulty performing motor skills and a decline in physical activity (PA) level and low enjoyment of PA. We aimed to evaluate whether longitudinal practice of an activity in virtual and real environments improves motor performance and whether this improvement is transferred to a subsequent practice when changing the environment, promoting PA and providing enjoyment; (2) Methods: People with ASD, aged between 10 and 16 years, were included and distributed randomly into two opposite sequences. The participants performed a 10 session protocol, with five sessions practicing in each environment (virtual or real). Heart rate measurement was carried out and an enjoyment scale was applied; (3) Results: 22 participants concluded the protocol. Sequence A (virtual first) presented an improvement in accuracy and precision and transferred this when changing environment; they also had a greater change in heart rate reserve. The majority of participants reported "fun" and "great fun" levels for enjoyment; (4) Conclusions: The virtual reality activity presented a higher level of difficulty, with greater gains in terms of transference to the real environment. Considering PA, our task provided very light to light activity and the majority of participants enjoyed the task.

Communication skills in children aged 6-8 years, without cerebral palsy cooled for neonatal hypoxic-ischemic encephalopathy.

We assessed communication skills of 48 children without cerebral palsy (CP) treated with therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) (cases) compared to 42 controls at early school-age and examined their association with white matter diffusion properties in both groups and 18-month Bayley-III developmental assessments in cases. Parents completed a Children's Communication Checklist (CCC-2) yielding a General Communication Composite (GCC), structural and pragmatic language scores and autistic-type behavior score. GCC ≤ 54 and thresholds of structural and pragmatic language score differences defined language impairment. Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) was compared between 31 cases and 35 controls. Compared to controls, cases had lower GCC (p = 0.02), structural (p = 0.03) and pragmatic language score (p = 0.04) and higher language impairments (p = 0.03). GCC correlated with FA in the mid-body of the corpus callosum, the cingulum and the superior longitudinal fasciculus (p < 0.05) in cases. Bayley-III Language Composite correlated with GCC (r = 0.34, p = 0.017), structural (r = 0.34, p = 0.02) and pragmatic (r = 0.32, p = 0.03) language scores and autistic-type behaviors (r = 0.36, p = 0.01).

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy.

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

Training emotional recognition in a child with acquired brain injury: A single case study.

Emotional processing is affected by childhood brain injury. Ineffective emotional processing and poor understanding of social cues affect the development of social relationships leading to social isolation and a poorer quality of life in the long-term. Facial expression recognition is a non-verbal social cue that is used to interpret the thoughts and feelings of others. Children with brain injury have shown deficits identifying even basic emotions from facial expression, yet few intervention studies have explored how to develop facial expression recognition in children with brain injury. Enhancing the ability to recognize and interpret facial expressions for these children would have implications for their emotional processing and social-emotional behavior. In this paper we report on a short single case study intervention to increase facial expression recognition using the Facial Affect Recognition training (FAR) for a 10-year-old-child with brain injury. Following intervention, there was not only an increase in facial expression recognition but also changes in social-emotional behavior indicating some generalization to other contexts. The results suggest that rehabilitation of emotional processing difficulties may indeed be possible, and further intervention studies aimed at developing these skills in children with brain injury are warranted.

Clinical characteristics of children with congenital Zika syndrome: a case series.

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.

Clinical characteristics of children with congenital Zika syndrome: a case series / Características clínicas de crianças com síndrome do zika congênita: uma série de casos

ABSTRACT Background: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. Objective: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. Methods: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. Results: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. Discussion: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.

RESUMO Introdução: A síndrome congênita do zika envolve alterações estruturais do cérebro, incluindo ventriculomegalia, córtices finos do cérebro, padrão giral anormal, malformações corticais, hipoplasia do corpo caloso, atraso de mielinização, calcificações difusas subcorticais, hipoplasia do tronco cerebral e microcefalia em recém-nascidos. Objetivo: Este estudo teve como objetivo descrever as características clínicas de crianças com síndrome congênita do zika; comparar os resultados de bebês infectados no primeiro (1T, n=20) e no segundo trimestres da gravidez (2T, n=11); investigar correlações entre peso ao nascer, perímetro cefálico ao nascer e acompanhamento, idade gestacional ao nascer e escores motores brutos. Método: Os participantes foram avaliados com a Escala Motora Infantil de Alberta (Alberta Infant Motor Scale - AIMS) e a parte A da Medida da Função Motora Grossa (Gross Motor Function Measure - GMFM-A). A ANOVA comparou a circunferência da cabeça, a idade gestacional ao nascer, o peso ao nascer e o desempenho motor bruto de 1T e 2T. As correlações foram investigadas pelos coeficientes de correlação de Pearson. A ANOVA mostrou diferenças no perímetro cefálico ao nascimento e acompanhamento. A circunferência da cabeça foi menor no 1T, em comparação ao 2T. Resultados: O desempenho motor foi classificado como abaixo do quinto percentil na AIMS para todas as crianças e o 1T apresentou escores mais baixos na posição de bruços, sentado e no escore total da AIMS, em comparação ao 2T. As crianças variaram de 8 a 78% no GMFM-A e houve um desempenho motor pior de 1T. Dezenove crianças apresentaram hipertonia, seis apresentaram tônus normal e seis apresentaram hipotonia. A circunferência da cabeça no nascimento foi correlacionada com o controle postural em posição de bruços à AIMS. Discussão: O perímetro cefálico de acompanhamento foi correlacionado aos escores AIMS em posição de bruços, em supino e no escore total. Menor perímetro cefálico ao nascimento e acompanhamento indicaram pior controle postural. Crianças com síndrome congênita do zika apresentaram microcefalia ao nascimento e acompanhamento. Circunferências da cabeça menores e piores resultados motores foram observados no 1T. Os bebês apresentaram maus resultados visuais e motores. Foram encontradas correlações moderadas positivas entre o nascimento e a circunferência da cabeça de acompanhamento, e a função motora grossa.

Effectiveness of anodal transcranial direct current stimulation to improve muscle strength and motor functionality after incomplete spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: We aimed to investigate the effects of anodal transcranial direct current stimulation (tDCS) against sham on muscle strength and motor functionality after incomplete spinal cord injury (iSCI). SETTING: University of São Paulo, Brazil. METHODS: A preplanned protocol was registered (PROSPERO, CRD42016050444). Pubmed, Embase, Web of Science, Cochrane Central Library and BVS databases were searched independently by two authors up to March 2018. Cochrane Collaboration's Tool was used for the risk of bias assessments. Generic inverse variance and random-effects model were used to calculate pooled effect sizes (ES), 95% confidence intervals (CIs) and p-values in meta-analyses. RESULTS: Six randomized clinical trials met inclusion criteria (n = 78 iSCI individuals) and were included in the meta-analysis. Results showed a marginal significant pooled effect of active tDCS in improving motor functionality with a small ES (SMD = 0.26, 95% CI = -0.00 to 0.53, p = 0.05, I2 = 0%). On the other hand, the pooled effect of active tDCS on muscle strength did not reach statistical significance, in parallel with a small ES (SMD = 0.35, 95% CI = -0.21 to 0.92, p = 0.22, I2 = 0%) when compared with sham tDCS. No significant adverse events were reported. CONCLUSIONS: Overall, there was a significant effect of tDCS in improving motor functionality following iSCI. However, a small ES and the marginal p-value suggest that these results should be interpreted with caution. Further high-quality clinical trials are needed to support or refute the use of tDCS in daily clinical practice.

Use of Augmented Reality with a Motion-Controlled Game Utilizing Alphabet Letters and Numbers to Improve Performance and Reaction Time Skills for People with Autism Spectrum Disorder.

Augmented reality (AR) uses the real-world setting but enables a person to interact with virtual objects. In this study, we aimed to explore the use of alphabet letter and number in an AR task and its influence in reaction time in a population with autism spectrum disorders (ASD) compared with the performance of typical developing (TD) controls. We evaluated reaction time before and after AR tasks that consisted of identifying correct numbers and alphabet letters in 48 people with ASD and 48 with TD controls. Results indicate that total points for TD group were higher (M = 86.4 and M = 79.0) when compared with the ASD group (M = 54.5 and M = 51.5) for alphabet letters and numbers, respectively. Moreover, in analysis of reaction time results, only the ASD group showed an improvement in performance after the practice of an AR task. The control group was faster before (M = 553.7) and after (M = 560.5) when compared with the ASD group (M = 2616.0 and M = 2374.6, respectively). Despite the need for further studies, our results support that there is potential for clinical use of an AR task-based intervention for people with ASD.

School-age outcomes of children without cerebral palsy cooled for neonatal hypoxic-ischaemic encephalopathy in 2008-2010.

OBJECTIVE: Since therapeutic hypothermia became standard care for neonatal hypoxic-ischaemic encephalopathy (HIE), even fewer infants die or have disability at 18-month assessment than in the clinical trials. However, longer term follow-up of apparently unimpaired children is lacking. We investigated the cognitive, motor and behavioural performances of survivors without cerebral palsy (CP) cooled for HIE, in comparison with matched non-HIE control children at 6-8 years. DESIGN: Case-control study. PARTICIPANTS: 29 case children without CP, cooled in 2008-2010 and 20 age-matched, sex-matched and social class-matched term-born controls. MEASURES: Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire. RESULTS: Cases compared with controls had significantly lower mean (SD) full-scale IQ (91 [10.37]vs105[13.41]; mean difference (MD): -13.62, 95% CI -20.53 to -6.71) and total MABC-2 scores (7.9 [3.26]vs10.2[2.86]; MD: -2.12, 95% CI -3.93 to -0.3). Mean differences were significant between cases and controls for verbal comprehension (-8.8, 95% CI -14.25 to -3.34), perceptual reasoning (-13.9, 95% CI-20.78 to -7.09), working memory (-8.2, 95% CI-16.29 to -0.17), processing speed (-11.6, 95% CI-20.69 to -2.47), aiming and catching (-1.6, 95% CI-3.26 to -0.10) and manual dexterity (-2.8, 95% CI-4.64 to -0.85). The case group reported significantly higher median (IQR) total (12 [6.5-13.5] vs 6 [2.25-10], p=0.005) and emotional behavioural difficulties (2 [1-4.5] vs 0.5 [0-2.75], p=0.03) and more case children needed extra support in school (34%vs5%, p=0.02) than the control group. CONCLUSIONS: School-age children without CP cooled for HIE still have reduced cognitive and motor performance and more emotional difficulties than their peers, strongly supporting the need for school-age assessments.

"Must try harder." Is effort and performance validity testing a necessary part of pediatric neuropsychological assessment?

Neuropsychological assessments results have significant implications for pediatric populations, based upon the assumption that the young person has adopted an effortful approach and has engaged in assessment. There is a commonly-accepted risk to assuming the validity of neuropsychological assessment results with adults, and, therefore, performance validity testing (PVT) has become a major topic of research and investigation and has become an accepted part of routine assessment. The same approach has not been adopted in assessment with children and a paucity of studies has focused on PVT in children. We review studies that demonstrate that children are equal to adults in their ability to use deception and that clinicians cannot detect false-effort without use of validity tests. We explore how frequently such tests are used and how well they work in assessment with children, and the limits, complexities, and constraints of adapting adult tests. We advocate that adequate performance validity testing is essential in order to maximize confidence in the results and we hypothesize that assessment with pediatric populations should take into account a range of influences, such as neuro-developmental factors associated with age of the child and suitability of proposed measures according to the evidence-base.

Attention and visuo-spatial function in children without cerebral palsy who were cooled for neonatal encephalopathy: a case-control study.

Objectives: Dorsal-stream functions are vulnerable to early brain injury associated with neonatal encephalopathy (NE) following perinatal asphyxia, even in children not developing cerebral palsy (CP). Since therapeutic hypothermia (TH) became the standard treatment for NE, the incidence of CP is reduced but the impact on dorsal-stream functions is unknown. We aimed to compare dorsal-stream functions in TH-treated survivors of NE, without CP, with those of matched controls. Methods: We administered tests of dorsal-stream function to 29 case children aged 6-to-8 years treated with TH for NE and without CP, and 20 age, sex and social class matched controls. We used the Conner's Continuous Performance Test (CPT) 2nd Edition to assess attentiveness, based upon Hit Reaction Time (HRT) percentile score and HRT standard error percentile, the CPT HRT block change measure to assess sustained attention and the NEPSY-II block construction and arrows tests to assess visuo-spatial performance and mental rotation. Results: Case children performed significantly worse than controls on measures of attention and visuo-spatial function. Conclusions: Children given TH treatment for NE can have subtle attention difficulties with slower reaction times and reduced visuo-spatial processing. These findings illustrate the continued vulnerability of dorsal-stream functions following NE despite the use of TH.

Motor learning from virtual reality to natural environments in individuals with Duchenne muscular dystrophy.

PURPOSE: To examine whether performance improvements in the virtual environment generalize to the natural environment. STUDY DESIGN: we had 64 individuals, 32 of which were individuals with DMD and 32 were typically developing individuals. METHODS: The groups practiced two coincidence timing tasks. In the more tangible button-press task, the individuals were required to 'intercept' a falling virtual object at the moment it reached the interception point by pressing a key on the computer. In the more abstract task, they were instructed to 'intercept' the virtual object by making a hand movement in a virtual environment using a webcam. RESULTS AND CONCLUSIONS: For individuals with DMD, conducting a coincidence timing task in a virtual environment facilitated transfer to the real environment. However, we emphasize that a task practiced in a virtual environment should have higher rates of difficulties than a task practiced in a real environment. IMPLICATIONS FOR REHABILITATION Virtual environments can be used to promote improved performance in ?real-world? environments. Virtual environments offer the opportunity to create paradigms similar ?real-life? tasks, however task complexity and difficulty levels can be manipulated, graded and enhanced to increase likelihood of success in transfer of learning and performance. Individuals with DMD, in particular, showed immediate performance benefits after using virtual reality.

The Clinical Utility of Virtual Reality in Neurorehabilitation: A Systematic Review.

BACKGROUND: Virtual reality (VR) experiences (through games and virtual environments) are increasingly being used in physical, cognitive, and psychological interventions. However, the impact of VR as an approach to rehabilitation is not fully understood, and its advantages over traditional rehabilitation techniques are yet to be established. METHOD: We present a systematic review which was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). During February and March of 2018, we conducted searches on PubMed (Medline), Virtual Health Library Search Portal databases (BVS), Web of Science (WOS), and Embase for all VR-related publications in the past 4 years (2015, 2016, 2017, and 2018). The keywords used in the search were "neurorehabilitation" AND "Virtual Reality" AND "devices." RESULTS: We summarize the literature which highlights that a range of effective VR approaches are available. Studies identified were conducted with poststroke patients, patients with cerebral palsy, spinal cord injuries, and other pathologies. Healthy populations have been used in the development and testing of VR approaches meant to be used in the future by people with neurological disorders. A range of benefits were associated with VR interventions, including improvement in motor functions, greater community participation, and improved psychological and cognitive function. CONCLUSIONS: The results from this review provide support for the use of VR as part of a neurorehabilitation program in maximizing recovery.

Traumatic brain injury: a potential cause of violent crime?

Traumatic brain injury (TBI) is the biggest cause of death and disability in children and young people. TBI compromises important neurological functions for self-regulation and social behaviour and increases risk of behavioural disorder and psychiatric morbidity. Crime in young people is a major social issue. So-called early starters often continue for a lifetime. A substantial majority of young offenders are reconvicted soon after release. Multiple factors play a role in crime. We show how TBI is a risk factor for earlier, more violent, offending. TBI is linked to poor engagement in treatment, in-custody infractions, and reconviction. Schemes to assess and manage TBI are under development. These might improve engagement of offenders in forensic psychotherapeutic rehabilitation and reduce crime.

Motor performance of individuals with cerebral palsy in a virtual game using a mobile phone.

OBJECTIVES: Cerebral palsy (CP) is a permanent disorder of movement, muscle tone or posture that is caused by damage to the immature and developing brain. Research has shown that Virtual Reality (VR) technology can be used in rehabilitation to support the acquisition of motor skills and the achievement of functional tasks. The aim of this study was to explore for improvements in the performance of individuals with CP with practice in the use of a virtual game on a mobile phone and to compare their performance with that of the control group. MATERIALS AND METHODS: Twenty-five individuals with CP were matched for age and sex with twenty-five, typically developing individuals. Participants were asked to complete a VR maze task as fast as possible on a mobile phone. All participants performed 20 repetitions in the acquisition phase, five repetitions for retention and five more repetitions for transfer tests, in order to evaluate motor learning from the task. RESULTS: The CP group improved their performance in the acquisition phase and maintained the performance, which was shown by the retention test; in addition, they were able to transfer the performance acquired in an opposite maze path. The CP group had longer task-execution compared to the control group for all phases of the study. CONCLUSION: Individuals with cerebral palsy were able to learn a virtual reality game (maze task) using a mobile phone, and despite their differences from the control group, this kind of device offers new possibilities for use to improve function. Implications for rehabilitation A virtual game on a mobile phone can enable individuals with Cerebral Palsy (CP) to improve performance. This illustrates the potential for use of mobile phone games to improve function. Individuals with CP had poorer performance than individuals without CP, but they demonstrated immediate improvements from using a mobile phone device. Individuals with CP were able to transfer their skills to a similar task indicating that they were able to learn these motor skills by using a mobile phone game.

Effects of high-frequency transcranial magnetic stimulation on functional performance in individuals with incomplete spinal cord injury: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a new tool in neurological rehabilitation of individuals with spinal cord injury (SCI). However, due to the inconsistent results regarding the effects of rTMS in people with SCI, a randomized controlled double-blind crossover trial is needed to clarify the clinical utility and to assess the effect size of rTMS intervention in this population. Therefore, this paper describes a study protocol designed to investigate whether the use of rTMS can improve the motor and sensory function, as well as reduce spasticity in patients with incomplete SCI. METHODS: A double-blind randomized sham-controlled crossover trial will be performed by enrolling 20 individuals with incomplete SCI. Patients who are at least six months post incomplete SCI (aged 18-60 years) will be recruited through referral by medical practitioners or therapists. Individuals will be randomly assigned to either group 1 or group 2 in a 1:1 ratio, with ten individuals in each group. The rTMS protocol will include ten sessions of high-frequency rTMS (5 Hz) over the bilateral lower-limb motor area positioned at the vertex (Cz). Clinical evaluations will be performed at baseline and after rTMS active and sham. DISCUSSION: rTMS has produced positive results in treating individuals with physical impairments; thus, it might be promising in the SCI population. The results of this study may provide new insights to motor rehabilitation thereby contributing towards the better usage of rTMS in the SCI population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02899637 . Registered on 25 August 2016.

Is damage to the pre-frontal cortex dormant until adolescence, or difficult to detect? Looking for keys that unlock executive functions in children in the wrong place.

A range of functions can be negatively affected by pre-frontal cortex (PFC) injury, but observed behavioural and social changes are commonly linked to post-injury changes in executive function. Executive functioning is a complex neuropsychological construct which is further complicated by neuro-developmental processes when applied to children. There is a substantial and continuing evidence base that supports the view that early childhood pre-frontal cortex (PFC) injury results in hidden, dormant, or sleeping effects. In contrast, recent and rapidly accruing contemporary studies provide preliminary evidence that challenge the view that PFC associated impairments are completely 'hidden'. Studies that examine the various functions of the PFC and differentiate these to provide preliminary evidence to indicate earlier EF development than that which develops upon reaching adolescence, are reviewed here, together with research that identifies early predictors of later EF impairments. It remains that studies of PFC function and/or structural brain-changes are substantially complicated by issues related to definition regarding functions of the PFC, measurement of EF and other PFC-related functions that may be better understood as meta-processes. These issues are discussed in the concluding sections of this paper.