Longitudinal brain volumetrics in glioma survivors.

OBJECTIVE: Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT. METHODS: This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models. RESULTS: The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36-18.9 years), and the median number of time points analyzed per patient was 12 (range 2-40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (ß = -0.06, p < 0.001) and use of RT (ß = -1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (ß = -0.08, p < 0.001), midline involvement (ß = 1.31, p = 0.006), and use of RT (ß = -1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (ß = -0.0027, p = 0.001), tumor resection (ß = -0.069, p < 0.001), use of chemotherapy (ß = -0.0597, p = 0.003), and use of RT (ß = -0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model. CONCLUSIONS: This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

Adaptive functioning and academic achievement in pediatric survivors of acute lymphoblastic leukemia: Associations with executive functioning, socioeconomic status, and academic support.

OBJECTIVES: This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review. RESULTS: Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02). CONCLUSIONS: Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development.

Volumetric brain assessment of long-term head and neck cancer survivors.

BACKGROUND: Radiation therapy (RT) for locally advanced head and neck cancer (HNC) often exposes subcortical brain structures to radiation. We performed this study to assess region-specific brain volumetrics in a population of long term HNC survivors. METHODS AND MATERIALS: Forty HNC survivors were enrolled at a mean of 6.4 years from completion of RT. Patients underwent a research MRI protocol that included a 3D T1- weighted whole-brain scan on a 3 Tesla MRI scanner. Voxel based morphometry was performed using the Computational Anatomy Toolbox with the Neuromorphometrics atlas. Healthy controls from the Human Connectome Project were used as a comparison cohort. Study participants also completed a comprehensive neurocognitive assessment. RESULTS: The final study cohort consisted of 38 participants after excluding 2 participants due to image quality. HNC survivors displayed widespread reduction in gray matter (GM) brain region volumes that included bilateral medial frontal cortex, temporal lobe, hippocampus, supplemental motor area, and cerebellum. Greater radiation exposure was associated with reduced GM volume in the left ventral diencephalon (r = -0.512, p = 0.003). Associations between cognition and regional GM volumes were identified for motor coordination and bilateral cerebellum (left, r = 0.444, p = 0.009; right, r = 0.372, p = 0.030), confrontation naming and left amygdala (r = 0.382, p = 0.026), verbal memory and bilateral thalamus (left, r = 0.435, p = 0.010; right, r = 0.424, p = 0.012), right amygdala (r = 0.339, p = 0.050), and right putamen (r = 0.364, p = 0.034). CONCLUSIONS: Reductions in GM were observed within this cohort of primarily non-nasopharyngeal HNC survivors as compared to a control sample. GM volumes were associated with performance in multiple cognitive domains. Results of this exploratory study support the need for investigation of anatomic brain changes as an important translational corollary to cognitive problems among HNC survivors.

Inflammation, Executive Function, and Adiposity in Children With or at Risk for Obesity: A Pilot Study.

OBJECTIVE: Obesity is associated with executive function (EF) deficits across the lifespan. Higher body mass index (BMI), obesity severity, and poorer adherence and weight outcomes in obesity treatment have all been associated with EF deficits. Adult literature has begun to emphasize neuroinflammation in obesity as a possible pathway to later cognitive impairment in EF. However, pediatric obesity literature has yet to establish associations between peripheral inflammation and EF. Thus, the present study examined associations and variability in inflammation, EF, and adiposity in children with or at risk for obesity. Additionally, inflammation was examined as a mediator of the relationship between adiposity and EF. METHODS: Children (N = 39) aged 8-12 years with BMI ≥ 50th percentile were recruited. The NIH Toolbox Cognitive Battery was used to assess performance-based EF. Peripheral inflammation was assessed in fasted sera. Dual-energy X-ray absorptiometry scans were conducted to assess body composition. Linear regression and Hayes' PROCESS Model 4 (Hayes, 2017) were used to evaluate associations between adiposity and inflammation, inflammation and EF, and whether adiposity effects EF through its effect on inflammation. RESULTS: Positive associations were identified between adiposity and inflammation, and negative to null associations were identified between inflammation and EF. Medium indirect effects of adiposity on EF through inflammation were detected. CONCLUSION: Pilot evidence suggests greater adiposity is linked with greater inflammation, which in turn is associated with less EF in some domains. Directionality and causality cannot yet be established, but with replication, findings may inform efforts to target EF in pediatric obesity.

A biobehavioural and social-structural model of inflammation and executive function in pediatric chronic health conditions.

ABSTRACTEvidence indicates that pediatric chronic health conditions (CHCs) often impair executive functioning (EF) and impaired EF undermines pediatric CHC management. This bidirectional relationship likely occurs due to biobehavioural and social-structural factors that serve to maintain this feedback loop. Specifically, biobehavioural research suggests that inflammation may sustain a feedback loop that links together increased CHC severity, challenges with EF, and lower engagement in health promoting behaviours. Experiencing social and environmental inequity also maintains pressure on this feedback loop as experiencing inequities is associated with greater inflammation, increased CHC severity, as well as challenges with EF and engagement in health promoting behaviours. Amidst this growing body of research, a model of biobehavioural and social-structural factors that centres inflammation and EF is warranted to better identify individual and structural targets to ameliorate the effects of CHCs on children, families, and society at large. This paper proposes this model, reviews relevant literature, and delineates actionable research and clinical implications.

Processing efficiency in pediatric cancer survivors: A review and operationalization for outcomes research and clinical utility.

OBJECTIVE: Childhood cancer and cancer-related treatments disrupt brain development and maturation, placing survivors at risk for cognitive late effects. Given that assessment tools vary widely across researchers and clinicians, it has been daunting to identify distinct patterns in outcomes across diverse cancer types and to implement systematic neurocognitive screening tools. This review aims to operationalize processing efficiency skill impairment-or inefficient neural processing as measured by working memory and processing speed abilities-as a worthwhile avenue for continued study within the context of childhood cancer. METHODS: A comprehensive literature review was conducted to examine the existing research on cognitive late effects and biopsychosocial risk factors in order to conceptualize processing efficiency skill trends in childhood cancer survivors. RESULTS: While a frequently reported pattern of neurobiological (white matter) and cognitive (working memory and processing speed) disruption is consistent with processing efficiency skill impairment, these weaknesses have not yet been fully operationalized in this population. We offer a theoretical model that highlights the impacts of a host of biological and environmental factors on the underlying neurobiological substrates of cancer survivors that precede and may even predict long-term cognitive outcomes and functional abilities following treatment. CONCLUSION: The unified construct of processing efficiency may be useful in assessing and communicating neurocognitive skills in both outcomes research and clinical practice. Deficits in processing efficiency may serve as a possible indicator of cognitive late effects and functional outcomes due to the unique relationship between processing efficiency skills and neurobiological disruption following cancer treatment. Continued research along these lines is crucial for advancing childhood cancer outcomes research and improving quality of life for survivors.

The association between sleep disturbances and neurocognitive function in pediatric sickle cell disease.

BACKGROUND AND OBJECTIVE: Youth with sickle cell disease (SCD) without neurological complications continue to be at increased risk of neurocognitive difficulties. Nocturnal hypoxemia is associated with neurocognitive outcomes and has been identified as a chronic complication in youth with SCD. The objective of this study was to assess the relationship between sleep disturbances and neurocognitive functioning in youth with SCD, while taking into account demographic and socioeconomic factors. METHODS: Youth with SCD were identified through retrospective chart review who underwent a standardized polysomnography (PSG) and completed a neuropsychological testing battery to assess cognitive skills, including verbal comprehension, working memory, processing speed, and cognitive flexibility. Questionnaires were also collected to assess parent-reported concerns with their youth's executive and adaptive skills. RESULTS: Twenty-seven youth with SCD, ages 6-17, were identified who completed both a PSG and neuropsychological testing. Results demonstrated that verbal comprehension decreased by 2.37 standard points for every unit decrease in mean nocturnal oxygen saturation (SpO2) (p = 0.031). Working memory was also found to decrease by 1.46 standard points for each 1% increase in time spent under 90% oxygen saturation (pTST SpO2 < 90%) (p = 0.030). Sleep parameters did not significantly predict other cognitive scores or parent-reported executive or behavioral ratings. CONCLUSION: Our study found that sleep disturbance, mean nocturnal SpO2 and pTST SpO2 < 90%, significantly affected verbal comprehension and working memory performance, respectively. Overall, these findings have the potential to identify sleep needs in youth with SCD to promote sleep-targeted interventions as a modifiable factor to reduce neurocognitive deficits.

Self-endorsed cognitive problems versus objectively assessed cognitive impairment in blood or bone marrow transplantation recipients: A longitudinal study.

BACKGROUND: Cognitive impairment in survivors of blood or bone marrow transplantation (BMT) is well documented. However, to the authors' knowledge, the clinical relevance of self-endorsed cognitive problems and their relation to objectively assessed cognitive impairment is not known. METHODS: The authors assessed cognitive impairment in 378 BMT recipients (median age, 52.2 years, 40% of whom were female and 68% of whom were non-Hispanic white) and 98 healthy controls at 5 predetermined time points: at baseline (before BMT) and at 6 months, 1 year, 2 years, and 3 years after BMT. Self-endorsed cognitive problems were evaluated using the Neuropsychological Impairment Scale (NIS) and correlated with a standardized 2-hour battery of objective cognitive testing at each time point. The authors examined the magnitude of difference in self-endorsed cognitive problems between BMT recipients and healthy controls, and the rate of change in scores over time. Multivariable analyses were used to identify clinical and/or demographic variables associated with self-endorsed cognitive problems. The authors also examined the association between cognitive impairment and returning to work after BMT. RESULTS: Compared with healthy controls, BMT recipients endorsed more cognitive problems (P < .001) at all time points, and the rate of change in NIS scores was found to be significantly greater in BMT recipients. Fatigue was associated with greater endorsement of cognitive problems at 1 year after BMT (odds ratio, 4.23; 95% CI, 2.1-8.3 [P < .001]). Overall, there was a statistically significant, modest correlation noted between self-endorsed cognitive problems and objective cognitive impairment (range, 0.401-0.445 [P ≤ .01]). Higher self-endorsed cognitive problems were associated with a 3.7-fold (P = .02) higher odds of not returning to work at 3 years after BMT. CONCLUSIONS: The results of the current study demonstrated that self-endorsed cognitive problems can help to identify vulnerable patient subpopulations for detailed cognitive assessment and possible cognitive remediation.

The efficacy of a pilot pediatric cognitive remediation summer program to prepare for transition of care.

This study assessed the efficacy of a time-sensitive cognitive remediation summer program (CRSP) that provided patients and their families with tools to help mitigate neurocognitive deficits and promote independence to foster precursor transition of medical care skills. A total of 38 participants (aged 9-15) were included in one of the CRSPs offered yearly from 2013 to 2016. A longitudinal design was employed and at each evaluation time point, one week before start of the CRSP (pre-testing) and within three weeks after the end of the program (post-testing)), participants were administered measures of executive functioning in addition to parent ratings of behavior, executive functioning, and adaptive skills (Year 1-Year 4). In Year 4, additional measures were collected, including parenting style and parent engagement and involvement in the program. Results from Year 1 to Year 4 (n = 35) demonstrated that participants in the CRSP showed significant improvement on neuropsychological testing in sustained and selective attention, planning, and cognitive flexibility. Robust changes in parent ratings of adaptive functioning from pre- to post-treatment were also found. Specific to Year 4 (n = 13), results revealed that participants showed improvement in levels of independence with at least one of the individualized goals focused on during the program. This study provided a systematic method to gauge the levels of instruction necessary to reach goals, a crucial tool in skill-teaching. Overall, our study provides evidence for the efficacy of the CRSP and validates a feasible intervention that can be integrated into standard of care for pediatric medical populations.

Longitudinal Changes in Resting State Connectivity and White Matter Integrity in Adolescents With Sports-Related Concussion.

OBJECTIVES: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. METHODS: We assessed male high school football players (ages 14-18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. RESULTS: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. CONCLUSIONS: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781-792).

Effects of Developmental Age on Symptom Reporting and Neurocognitive Performance in Youth After Sports-Related Concussion Compared to Control Athletes.

There is increased necessity to focus research on school-aged athletes with sports-related concussion (SRC). This study assessed differences in symptom reporting and neurocognitive performance in youth athletes who sustained a sports-related concussion. A total of 1345 concussed and 3529 nonconcussed athletes (ages 8-21) completed the Immediate Post-concussive Assessment and Cognitive Testing (ImPACT). Analyses of covariance were conducted in order to assess differences in neurocognitive performance and symptom reporting between the sports-related concussion and control groups across age ranges. Longitudinal hierarchical linear modeling was employed to examine age and its relationship with rates of sports-related concussion recovery in neurocognitive performance. Results revealed athletes aged 13 to 15 had significantly lower neurocognitive performance scores compared to same-aged athletes without a history of sports-related concussion. With respect to the hierarchical linear modeling results, age was identified as a unique predictor of symptom recovery, particularly for ages 8 to 12. Results provide a better understanding of typical symptom reporting and neurocognitive outcomes for younger athletes across different ages.

Differential recruitment of theory of mind brain network across three tasks: An independent component analysis.

Social neuroscience research has focused on an identified network of brain regions primarily associated with processing Theory of Mind (ToM). However, ToM is a broad cognitive process, which encompasses several sub-processes, such as mental state detection and intentional attribution, and the connectivity of brain regions underlying the broader ToM network in response to paradigms assessing these sub-processes requires further characterization. Standard fMRI analyses which focus only on brain activity cannot capture information about ToM processing at a network level. An alternative method, independent component analysis (ICA), is a data-driven technique used to isolate intrinsic connectivity networks, and this approach provides insight into network-level regional recruitment. In this fMRI study, three complementary, but distinct ToM tasks assessing mental state detection (e.g. RMIE: Reading the Mind in the Eyes; RMIV: Reading the Mind in the Voice) and intentional attribution (Causality task) were each analyzed using ICA in order to separately characterize the recruitment and functional connectivity of core nodes in the ToM network in response to the sub-processes of ToM. Based on visual comparison of the derived networks for each task, the spatiotemporal network patterns were similar between the RMIE and RMIV tasks, which elicited mentalizing about the mental states of others, and these networks differed from the network derived for the Causality task, which elicited mentalizing about goal-directed actions. The medial prefrontal cortex, precuneus, and right inferior frontal gyrus were seen in the components with the highest correlation with the task condition for each of the tasks highlighting the role of these regions in general ToM processing. Using a data-driven approach, the current study captured the differences in task-related brain response to ToM in three distinct ToM paradigms. The findings of this study further elucidate the neural mechanisms associated with mental state detection and causal attribution, which represent possible sub-processes of the complex construct of ToM processing.

Assessment of Sleep Quantity and Sleep Disturbances During Recovery From Sports-Related Concussion in Youth Athletes.

OBJECTIVE: To determine the relation between sleep quantity and sleep disturbances on symptoms and neurocognitive ability during the acute phase (<7d) and after sports-related concussion (SRC; >21d). DESIGN: Prospective inception cohort study. SETTING: General community setting of regional middle and high schools. PARTICIPANTS: A sample (N=971) including youth athletes with SRC (n=528) and controls (n=443) (age, 10-18y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Athletes completed the Immediate Post-Concussion Assessment and Cognitive Testing battery. Partial correlation analyses and independent t tests were conducted to assess sleep quantity the night before testing. Multivariate analysis of covariance was used to assess sleep disturbances and their interaction with age. RESULTS: Less sleep quantity was correlated with greater report of cognitive (P=.001) and neuropsychological (P=.024) symptoms specific to prolonged recovery from SRC. Sleep disturbances significantly affect each migraine, cognitive, and neuropsychological symptoms (P<.001). A significant interaction was found between sleep disturbances and age (P=.04) at >21 days post-SRC. CONCLUSIONS: Findings emphasize that the continued presence of low sleep quantity and sleep disturbances in youth athletes with SRC should be a specific indicator to health professionals that these athletes are at an increased risk of protracted recovery. Further research should identify additional factors that may interact with sleep to increase the risk of protracted recovery.

Brain Mechanisms Underlying Reading the Mind from Eyes, Voice, and Actions.

Evidence from cognitive and social neuroscience research suggests that Theory of Mind (ToM), the ability to attribute mental states to others, is mediated by a group of brain regions collectively known as the ToM network. Nevertheless, there is significant variability in the functional activation of regions within this network across tasks. The goal of the present functional magnetic resonance imaging (fMRI) study was to examine the common and differential neural mechanisms of two aspects of ToM processing (emotion/mental-state recognition and intentional attribution) using three distinct, but complementary ToM tasks (Reading the Mind in the Eyes (RMIE), Reading the Mind in the Voice (RMIV), and Intentional Causal Attribution) in healthy adults. Participant accuracy was significantly worse in the ToM compared to the control condition across all tasks. Brain activation analyses replicated previously reported activation in inferior frontal gyrus (IFG) and middle temporal gyrus extending to posterior superior temporal sulcus (pSTS) in RMIE. Activation in the fusiform gyrus and bilateral middle temporal gyrus extending to temporo-parietal junction (TPJ) was unique to causality task. A region-of-interest analysis revealed shared activation in left IFG for RMIE and RMIV as well as TPJ recruitment specific to the causality task. The role of right TPJ in the causality task was further supported by a percent signal change analysis. A conjunction analysis revealed overlap in left IFG, left precentral gyrus, and left superior frontal gyrus activity across all tasks. These findings highlight common and differential recruitment of ToM regions according to task demand.

From word reading to multisentence comprehension: Improvements in brain activity in children with autism after reading intervention.

BACKGROUND: Children with ASD show a unique reading profile characterized by decoding abilities equivalent to verbal abilities, but with lower comprehension skills. Neuroimaging studies have found recruitment of regions primarily associated with visual processing (e.g., fusiform gyrus and medial parietal cortex), but reduced activation in frontal and temporal regions, when reading in adults with ASD. The purpose of this study was to assess neural changes associated with an intense reading intervention program in children with ASD using three fMRI tasks of reading. METHODS: 25 children with ASD were randomly assigned to a treatment (ASD-EXP) or waitlist group (ASD-WLC). Children participated in a reading intervention program (4-hour sessions per day, 5 days a week for 10 weeks). We utilized three tasks: word, sentence, and multisentence processing, each with differential demands of reading comprehension. fMRI data were acquired at each of two scanning sessions 10-weeks apart. RESULTS: Across tasks, post-intervention results revealed that the ASD-EXP group showed greater activation in bilateral precentral gyrus and the postcentral gyrus, visual processing regions (e.g., occipital cortex, fusiform gyrus), and frontal regions. In the word task, left thalamus and the right angular gyrus (AG) activation was unique to the ASD-EXP group post-intervention. Sentence tasks showed differential activation of core language areas (e.g., IFG, IPL) post-intervention. CONCLUSIONS: Our results provide evidence for differential recruitment of brain regions based on task demands in children with ASD, and support the potential of targeted interventions to alter brain activation in response to positive gains in treatment. Children with ASD have a different reading profile from other reading disorders that needs to be specifically targeted in interventions.

Changes in intrinsic local connectivity after reading intervention in children with autism.

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.

"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing.

The Impact of Reading Intervention on Brain Responses Underlying Language in Children With Autism.

Deficits in language comprehension have been widely reported in children with autism spectrum disorders (ASD), with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension. However, no study to date, has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in ASD. This study used a translational neuroimaging approach to test the role of a visual imagery-based reading intervention in improving the brain circuitry underlying language processing in children with ASD. Functional magnetic resonance imaging (MRI), in a longitudinal study design, was used to investigate intervention-related change in sentence comprehension, brain activation, and functional connectivity in three groups of participants (age 8-13 years): an experimental group of ASD children (ASD-EXP), a wait-list control group of ASD children (ASD-WLC), and a group of typically developing control children. After intervention, the ASD-EXP group showed significant increase in activity in visual and language areas and right-hemisphere language area homologues, putamen, and thalamus, suggestive of compensatory routes to increase proficiency in reading comprehension. Additionally, ASD children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between left-hemisphere language areas, the middle temporal gyrus and inferior frontal gyrus while reading high imagery sentences. Thus, the findings of this study, which support the principles of dual coding theory [Paivio 2007], suggest the potential of a strength-based reading intervention in changing brain responses and facilitating better reading comprehension in ASD children.