Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.

Brain connectivity and academic skills in English learners.

English learners (ELs) are a rapidly growing population in schools in the United States with limited experience and proficiency in English. To better understand the path for EL's academic success in school, it is important to understand how EL's brain systems are used for academic learning in English. We studied, in a cohort of Hispanic middle-schoolers (n = 45, 22F) with limited English proficiency and a wide range of reading and math abilities, brain network properties related to academic abilities. We applied a method for localizing brain regions of interest (ROIs) that are group-constrained, yet individually specific, to test how resting state functional connectivity between regions that are important for academic learning (reading, math, and cognitive control regions) are related to academic abilities. ROIs were selected from task localizers probing reading and math skills in the same participants. We found that connectivity across all ROIs, as well as connectivity of just the cognitive control ROIs, were positively related to measures of reading skills but not math skills. This work suggests that cognitive control brain systems have a central role for reading in ELs. Our results also indicate that an individualized approach for localizing brain function may clarify brain-behavior relationships.

GABAergic circuits of the basolateral amygdala and generation of anxiety after traumatic brain injury.

Traumatic brain injury (TBI) has reached epidemic proportions around the world and is a major public health concern in the United States. Approximately 2.8 million individuals sustain a traumatic brain injury and are treated in an Emergency Department yearly in the U.S., and about 50,000 of them die. Persistent symptoms develop in 10-15% of the cases including neuropsychiatric disorders. Anxiety is the second most common neuropsychiatric disorder that develops in those with persistent neuropsychiatric symptoms after TBI. Abnormalities or atrophy in the temporal lobe has been shown in the overwhelming number of TBI cases. The basolateral amygdala (BLA), a temporal lobe structure that consolidates, stores and generates fear and anxiety-based behavioral outputs, is a critical brain region in the anxiety circuitry. In this review, we sought to capture studies that characterized the relationship between human post-traumatic anxiety and structural/functional alterations in the amygdala. We compared the human findings with results obtained with a reproducible mild TBI animal model that demonstrated a direct relationship between the alterations in the BLA and an anxiety-like phenotype. From this analysis, both preliminary insights, and gaps in knowledge, have emerged which may open new directions for the development of rational and more efficacious treatments.

Cortical Thickness and Local Gyrification in Children with Developmental Dyslexia.

Developmental dyslexia is frequently associated with atypical brain structure and function within regions of the left hemisphere reading network. To date, few studies have employed surface-based techniques to evaluate cortical thickness and local gyrification in dyslexia. Of the existing cortical thickness studies in children, many are limited by small sample size, variability in dyslexia identification, and the recruitment of prereaders who may or may not develop reading impairment. Further, no known study has assessed local gyrification index (LGI) in dyslexia, which may serve as a sensitive indicator of atypical neurodevelopment. In this study, children with dyslexia (n = 31) and typically decoding peers (n = 45) underwent structural magnetic resonance imaging to assess whole-brain vertex-wise cortical thickness and LGI. Children with dyslexia demonstrated reduced cortical thickness compared with controls within previously identified reading areas including bilateral occipitotemporal and occipitoparietal regions. Compared with controls, children with dyslexia also showed increased gyrification in left occipitotemporal and right superior frontal cortices. The convergence of thinner and more gyrified cortex within the left occipitotemporal region among children with dyslexia may reflect its early temporal role in processing word forms, and highlights the importance of the ventral stream for successful word reading.

Control Engagement During Sentence and Inhibition fMRI Tasks in Children With Reading Difficulties.

Recent reading research implicates executive control regions as sites of difference in struggling readers. However, as studies often employ only reading or language tasks, the extent of deviation in control engagement in children with reading difficulties is not known. The current study investigated activation in reading and executive control brain regions during both a sentence comprehension task and a nonlexical inhibitory control task in third-fifth grade children with and without reading difficulties. We employed both categorical (group-based) and individual difference approaches to relate reading ability to brain activity. During sentence comprehension, struggling readers had less activation in the left posterior temporal cortex, previously implicated in language, semantic, and reading research. Greater negative activity (relative to fixation) during sentence comprehension in a left inferior parietal region from the executive control literature correlated with poorer reading ability. Greater comprehension scores were associated with less dorsal anterior cingulate activity during the sentence comprehension task. Unlike the sentence task, there were no significant differences between struggling and nonstruggling readers for the nonlexical inhibitory control task. Thus, differences in executive control engagement were largely specific to reading, rather than a general control deficit across tasks in children with reading difficulties, informing future intervention research.

Cognitive, Intervention, and Neuroimaging Perspectives on Executive Function in Children With Reading Disabilities.

The role of executive function (EF) in the reading process, and in those with reading difficulties, remains unclear. As members of the Texas Center for Learning Disabilities, we review multiple perspectives regarding EF in reading and then summarize some of our recent studies of struggling and typical readers in grades 3-5. Study 1a found that a bi-factor structure best represented a comprehensive assessment of EF. Study 1b found that cognitive and behavioral measures of EF related independently to math and reading. Study 1c found that EF related to reading, above and beyond other variables, but Study 1d found no evidence that adding an EF training component improved intervention response. Study 1e found that pretest EF abilities did not relate to intervention response. Neuroimaging studies examined EF-related brain activity during both reading and nonlexical EF tasks. In Study 2a, the EF task evoked control activity, but generated no differences between struggling and typical readers. The reading task, however, had group differences in both EF and reading regions. In Study 2b, EF activity during reading at pretest was related to intervention response. Across studies, EF appears involved in the reading process. There is less evidence for general EF predicting or improving intervention outcomes.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.

Longitudinal diffusion tensor imaging after pediatric traumatic brain injury: Impact of age at injury and time since injury on pathway integrity.

Following pediatric traumatic brain injury (TBI), longitudinal diffusion tensor imaging may characterize alterations in initial recovery and subsequent trajectory of white matter development. Our primary aim examined effects of age at injury and time since injury on pathway microstructure in children ages 6-15 scanned 3 and 24 months after TBI. Microstructural values generated using tract-based spatial statistics extracted from core association, limbic, and projection pathways were analyzed using general linear mixed models. Relative to children with orthopedic injury, the TBI group had lower fractional anisotropy (FA) bilaterally in all seven pathways. In left-hemisphere association pathways, school-aged children with TBI had the lowest initial pathway integrity and showed the greatest increase in FA over time suggesting continued development despite incomplete recovery. Adolescents showed limited change in FA and radial diffusivity and had the greatest residual deficit suggesting relatively arrested development. Radial diffusivity was persistently elevated in the TBI group, implicating dysmyelination as a core contributor to chronic post-traumatic neurodegenerative changes. The secondary aim compared FA values over time in the total sample, including participants contributing either one or two scans to the analysis, to the longitudinal cases contributing two scans. For each pathway, FA values and effect sizes were very similar and indicated extremely small differences in measurement of change over time in the total and longitudinal samples. Statistical approaches incorporating missing data may reliably estimate the effects of TBI and provide increased power to identify whether pathways show neurodegeneration, arrested development, or continued growth following pediatric TBI. Hum Brain Mapp 37:3929-3945, 2016. © 2016 Wiley Periodicals, Inc.

Functional significance of atypical cortical organization in spina bifida myelomeningocele: relations of cortical thickness and gyrification with IQ and fine motor dexterity.

The cortex in spina bifida myelomeningocele (SBM) is atypically organized, but it is not known how specific features of atypical cortical organization promote or disrupt cognitive and motor function. Relations of deviant cortical thickness and gyrification with IQ and fine motor dexterity were investigated in 64 individuals with SBM and 26 typically developing (TD) individuals, aged 8-28 years. Cortical thickness and 3D local gyrification index (LGI) were quantified from 33 cortical regions per hemisphere using FreeSurfer. Results replicated previous findings, showing regions of higher and lower cortical thickness and LGI in SBM relative to the TD comparison individuals. Cortical thickness and LGI were negatively associated in most cortical regions, though less consistently in the TD group. Whereas cortical thickness and LGI tended to be negatively associated with IQ and fine motor outcomes in regions that were thicker or more gyrified in SBM, associations tended to be positive in regions that were thinner or less gyrified in SBM. The more deviant the levels of cortical thickness and LGI-whether higher or lower relative to the TD group-the more impaired the IQ and fine motor outcomes, suggesting that these cortical atypicalities in SBM are functionally maladaptive, rather than adaptive.

Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children.

Background: The biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes. Methods: The participants were 52 children of Mexican or Central American origin aged 11.6-15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood. Results: Overall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures. Conclusions: Assessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance.

Volumetric analysis of regional variability in the cerebellum of children with dyslexia.

Cerebellar deficits and subsequent impairment in procedural learning may contribute to both motor difficulties and reading impairment in dyslexia. We used quantitative magnetic resonance imaging to investigate the role of regional variation in cerebellar anatomy in children with single-word decoding impairments (N = 23), children with impairment in fluency alone (N = 8), and typically developing children (N = 16). Children with decoding impairments (dyslexia) demonstrated no statistically significant differences in overall grey and white matter volumes or cerebellar asymmetry; however, reduced volume in the anterior lobe of the cerebellum relative to typically developing children was observed. These results implicate cerebellar involvement in dyslexia and establish an important foundation for future research on the connectivity of the cerebellum and cortical regions typically associated with reading impairment.

Brain Engagement During a Cognitive Flexibility Task Relates to Academic Performance in English Learners.

English Learners (ELs), students from non-English-speaking backgrounds, are a fast-growing, understudied, group of students in the U.S. with unique learning challenges. Cognitive flexibility-the ability to switch between task demands with ease-may be an important factor in learning for ELs as they have to manage learning in their non-dominant language and access knowledge in multiple languages. We used functional MRI to measure cognitive flexibility brain activity in a group of Hispanic middle school ELs (N = 63) and related it to their academic skills. We found that brain engagement during the cognitive flexibility task was related to both out-of-scanner reading and math measures. These relationships were observed across the brain, including in cognitive control, attention, and default mode networks. This work suggests the real-world importance of cognitive flexibility for adolescent ELs, where individual differences in brain engagement were associated with educational outcomes.

Autologous cellular therapy for cerebral palsy: a randomized, crossover trial.

We examined an autologous mononuclear-cell-therapy-based approach to treat cerebral palsy using autologous umbilical cord blood or bone-marrow-derived mononuclear cells. The primary objective was to determine if autologous cells are safe to administer in children with cerebral palsy. The secondary objectives were to determine if there was improvement in motor function of patients 12 months after infusion using the Gross Motor Function Measure and to evaluate impact of treatment on corticospinal tract microstructure as determined by radial diffusivity measurement. This Phase 1/2a trial was a randomized, blinded, placebo-controlled, crossover study in children aged 2-10 years of age with cerebral palsy enrolled between November 2013 and November 2016. Participants were randomized to 2:1 treatment:placebo. Treatment was either autologous bone-marrow-derived mononuclear cells or autologous umbilical cord blood. All participants who enrolled and completed their baseline visit planned to return for follow-up visits at 6 months, 12 months and 24 months after the baseline visit. At the 12-month post-treatment visit, participants who originally received the placebo received either bone-marrow-derived mononuclear cell or umbilical cord blood treatment. Twenty participants were included; 7 initially randomized to placebo, and 13 randomized to treatment. Five participants randomized to placebo received bone-marrow-derived mononuclear cells, and 2 received umbilical cord blood at the 12-month visit. None of the participants experienced adverse events related to the stem cell infusion. Cell infusion at the doses used in our study did not dramatically alter motor function. We observed concordant bilateral changes in radial diffusivity in 10 of 15 cases where each corticospinal tract could be reconstructed in each hemisphere. In 60% of these cases (6/10), concordant decreases in bilateral corticospinal tract radial diffusivity occurred post-treatment. In addition, 100% of unilateral corticospinal tract cases (3/3) exhibited decreased corticospinal tract radial diffusivity post-treatment. In our discordant cases (n = 5), directionality of changes in corticospinal tract radial diffusivity appeared to coincide with handedness. There was a significant improvement in corticospinal tract radial diffusivity that appears related to handedness. Connectivity strength increased in either or both pathways (corticio-striatal and thalamo-cortical) in each participant at 12 months post-treatment. These data suggest that both stem cell infusions are safe. There may be an improvement in myelination in some groups of patients that correlate with small improvements in the Gross Motor Function Measure scales. A larger autologous cord blood trial is impractical at current rates of blood banking. Either increased private banking or matched units would be required to perform a larger-scale trial.

Predicting behavioral deficits in pediatric traumatic brain injury through uncinate fasciculus integrity.

Behavioral dysregulation is a common and detrimental consequence of traumatic brain injury (TBI) in children that contributes to poor academic achievement and deficits in social development. Unfortunately, behavioral dysregulation is difficult to predict from either injury severity or early neuropsychological evaluation. The uncinate fasciculus (UF) connects orbitofrontal and anterior temporal lobes, which are commonly implicated in emotional and behavioral regulation. Using probabilistic diffusion tensor tractography (DTT), we examined the relationship between the integrity of the UF 3 months post-injury and ratings of executive functions 12 months post-injury in children with moderate to severe TBI and a comparison group with orthopedic injuries. As expected, fractional anisotropy of the UF was lower in the TBI group relative to the orthopedic injury group. DTT metrics from the UF served as a biomarker and predicted ratings of emotional and behavior regulation, but not metacognition. In contrast, the Glasgow Coma Scale score was not related to either UF integrity or to executive function outcomes. Neuroanatomical biomarkers like the uncinate fasciculus may allow for early identification of behavioral problems and allow for investigation into the relationship of frontotemporal networks to brain-behavior relationships.

Changes in maps of language function and the integrity of the arcuate fasciculus after therapy for chronic aphasia.

A patient with chronic aphasia secondary to unilateral stroke in the left hemisphere underwent language testing, diffusion tensor imaging (DTI), and functional imaging using magnetoencephalography (MEG) at four time points: 3 weeks prior to, immediately prior to, immediately after, and 3 months after Constraint Induced Language Therapy (CILT). Performance on language tests involving visual naming and repetition of spoken sentences improved between the immediately prior to and immediately after CILT testing sessions, but not between the pre-CILT sessions. MEG activation in putative pre-morbid language areas of the left hemisphere and homotopic areas of the right hemisphere increased immediately after therapy, as did integrity within the arcuate fasciculus bilaterally. These changes were not evident between the two pre-CILT sessions. While some of these functional, neurophysiological and structural changes had regressed 3 months after therapy, all remained at or above baseline levels. Results provide evidence for an association between improvement in functional status and the increased integrity within a white matter tract known to be involved in language function and its contralateral homologue, as well as increased neurophysiological activity in areas that have the potential to subserve language function bilaterally.

Cerebellar motor function in spina bifida meningomyelocele.

Spina bifida meningomyelocele (SBM), a congenital neurodevelopmental disorder, involves dysmorphology of the cerebellum, and its most obvious manifestations are motor deficits. This paper reviews cerebellar neuropathology and motor function across several motor systems well studied in SBM in relation to current models of cerebellar motor and timing function. Children and adults with SBM have widespread motor deficits in trunk, upper limbs, eyes, and speech articulators that are broadly congruent with those observed in adults with cerebellar lesions. The structure and function of the cerebellum are correlated with a range of motor functions. While motor learning is generally preserved in SBM, those motor functions requiring predictive signals and precise calibration of the temporal features of movement are impaired, resulting in deficits in smooth movement coordination as well as in the classical cerebellar triad of dysmetria, ataxia, and dysarthria. That motor function in individuals with SBM is disordered in a manner phenotypically similar to that in adult cerebellar lesions, and appears to involve similar deficits in predictive cerebellar motor control, suggests that age-based cerebellar motor plasticity is limited in individuals with this neurodevelopmental disorder.

The cerebellum in children with spina bifida and Chiari II malformation: Quantitative volumetrics by region.

Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction.

Behavioral and neurophysiologic response to therapy for chronic aphasia.

UNLABELLED: Breier JI, Juranek J, Maher LM, Schmadeke S, Men D, Papanicolaou AC. Behavioral and neurophysiologic response to therapy for chronic aphasia. OBJECTIVE: To characterize the relationship between neurophysiologic changes in the brain and behavioral response to constraint-induced language therapy (CILT) by using magnetoencephalography (MEG). DESIGN: Case series. SETTING: Medical school. PARTICIPANTS: Patients (N=23) with chronic aphasia after first-time unilateral stroke in the left hemisphere. INTERVENTIONS: Constraint-induced language therapy administered for 3 hours 4 times per week for 3 weeks. Language testing and functional imaging during a language comprehension task using MEG before, immediately after, and 3 months after CILT with a subgroup of patients undergoing additional MEG scanning and language testing 3 weeks before CILT. MAIN OUTCOME MEASURES: The percent of correct information units and the number of late dipoles normalized to total activation. RESULTS: Three patterns of behavioral and neurophysiologic response to CILT were identified. Patients with significant improvement in language immediately after CILT who lost these gains at follow-up had greater right hemisphere activation than other patients at all MEG scanning sessions. Patients with significant improvement in language immediately after CILT who maintained these gains at follow-up exhibited an increase in left temporal activation after CILT, whereas patients who did not exhibit significant improvement in language after CILT exhibited comparably greater activation in left parietal areas. CONCLUSIONS: Results suggest that although the right hemisphere may support recovery of language function in response to therapy, this recovery may not be stable, and some participation of perilesional areas of the left hemisphere may be necessary for a stable behavioral response.

Are primary and secondary types of brain anomalies exclusive factors affecting the attention networks in individuals with spina bifida?

OBJECTIVE: Individuals with spina bifida myelomeningocele (SBM) frequently exhibit cognitive impairments on tasks mediated by brain regions involved in the posterior attention network. Although such deficits have been historically assumed to result from primary and secondary brain insults, there is a dearth of literature regarding whether sequential versus simultaneous surgical closure of neural folds and surgical shunt placement affect neuropsychological function and brain structure of attention networks that have been widely studied in individuals with SBM. The current study addressed these gaps in a large cohort of children and adults with SBM. METHOD: White matter pathways and regional brain volumes of anterior and posterior attention networks were quantified through probabilistic tractography and automated segmentation, respectively. The Child Attention Network Test measured behavioral components of posterior and anterior attention networks. RESULTS: Sequential operations were associated with reduced orienting accuracy and smaller left superior parietal and dorsolateral prefrontal cortex volumes compared to simultaneous operations, controlling for a number of shunt revisions and age. Greater number of shunt revisions was associated with higher radial diffusivity values in the parietal tectocortical pathway. Older participants had greater accuracy and faster conflict resolution performance compared to younger participants, across operation type and number of shunt revisions. CONCLUSIONS: Shunt treatment and revision history related to brain structure and functions associated with the posterior attention network. Neurosurgical history also differentiated the harmful effects of early hydrocephalus on brain structure of the posterior from the anterior attention networks in SBM. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Brain activity in struggling readers before intervention relates to future reading gains.

Neural markers for reading-related changes in response to intervention could inform intervention plans by serving as a potential index of the malleability of the reading network in struggling readers. Of particular interest is the role of brain activation outside the reading network, especially in executive control networks important for reading comprehension. However, it is unclear whether any intervention-related executive control changes in the brain are specific to reading tasks or reflect more domain general changes. Brain changes associated with reading gains over time were compared for a sentence comprehension task as well as for a non-lexical executive control task (a behavioral inhibition task) in upper-elementary struggling readers, and in grade-matched non-struggling readers. Functional MRI scans were conducted before and after 16 weeks of reading intervention. Participants were grouped as improvers and non-improvers based on the consistency and size of post-intervention gains across multiple post-test measures. Engagement of the right fusiform during the reading task, both before and after intervention, was related to gains from remediation. Additionally, pre-intervention activation in regions that are part of the default-mode network (precuneus) and the fronto-parietal network (right posterior middle temporal gyrus) separated improvers and non-improvers from non-struggling readers. None of these differences were observed during the non-lexical inhibitory control task, indicating that the brain changes seen related to intervention outcome in struggling readers were specific to the reading process.