Relationships Among Structural Neuroimaging and Neurocognitive Outcomes in Adolescents and Young Adults with Congenital Heart Disease: A Systematic Review.

Congenital heart disease (CHD) is the most common cause of major congenital anomalies in the world. Disruptions to brain development in this population may impact cognitive outcomes. As individuals with CHD age, understanding of long-term neurocognitive and brain outcomes is essential. Synthesis of the current literature of brain-behavior relationships in adolescents and young adults with CHD is needed to understand long-term outcomes and identify literature gaps. This systematic review summarizes and integrates the current literature on the relationship between structural neuroimaging and neurocognitive outcomes in adolescents and young adults with CHD. Included papers were published through August 2, 2021. Searches were conducted on Pubmed and APA PsycInfo. Studies were eligible for inclusion if they evaluated adolescents or young adults (ages 10-35) with CHD, and without genetic comorbidity. Studies explored relationships among structural neuroimaging and neurocognitive outcomes, were in English, and were an empirical research study. A total of 22 papers were included in the current review. Data from each study was extracted and included in a table for comparison along with a systematic assessment of study quality. Results suggest worse brain outcomes (i.e., brain abnormality, reduced volume, lower fractional anisotropy, and brain topology) are related to poorer performance in neuropsychological domains of intelligence, memory, and executive functioning. Consistently, poorer memory performance was related to lower hippocampal and temporal region volumes. Statistically significant brain-behavior relationships in adolescents and young adults with CHD are generally observed across studies but there is a lack of consistency in investigated neuropsychological constructs and brain regions to be able to make specific conclusions. Further research with adult samples of CHD is needed to better understand the long-term impacts of early neurological insult.

The role of tax-filing status in uncovering socioeconomic and physical activity differences in college-aged students.

Objective:  This study examined relationships among multifaceted measures of socioeconomic status (SES) and physical activity (PA) in undergraduates. Participants were classified into dependent and independent tax filers to encapsulate the atypical divide in financial responsibility. Participants: 366 diverse American undergraduates. Methods: Participants completed an online survey including three SES metrics and the International Physical Activity Questionnaire. Results: Participants engaged in the same amount of total PA, albeit different proportions depending on SES measure and PA type. Independent tax filers engaged in more occupational PA than dependent tax filers, regardless of SES. Students with low SES engaged in less leisure-time PA than students with high SES. Conclusion: Household Material Hardship and SES proxy measures should be considered in the context of tax filing status among undergraduates. Greater precision with multifactorial SES measures will assist in providing the nuanced context when optimizing interventions and reducing barriers to increase PA in young adults.

White matter hyperintensities relate to executive dysfunction, apathy, but not disinhibition in long-term adult survivors of pediatric cerebellar tumor.

White matter hyperintensities (WMHs) have been related to executive dysfunction, apathy and disinhibition in a wide range of neurological populations. However, this relationship has not been examined in survivors of pediatric brain tumor. The goal of this study was to investigate how executive dysfunction, apathy, and disinhibition relate to WMHs in 31 long-term survivors of pediatric cerebellar brain tumor and 58 controls, using informant-report data from the Frontal Systems Behavior Scale. Total WMH volume was quantified using the Lesion Growth Algorithm. Further, periventricular, and subcortical volumes were identified based on proximity to custom ventricle masks generated in FSL. A ratio of WMH volume to whole brain volume was used to obtain normalized WMH volumes. Additionally, a multivariate regression analysis was performed. On average, informant-report scores were within normal limits and only executive dysfunction was significantly higher in survivors compared to controls (t(47.9) = -2.4, p=.023). Informants reported clinically significant levels of apathy in 32.3% of survivors. Informants also reported clinically significant executive dysfunction in 19.4 % of survivors and clinically significant disinhibition in, again, 19.4 % of survivors. Increased volume of WMHs was positively correlated with executive dysfunction (r = 0.33, p = 0.02) and apathy (r = 0.23, p = .04). Similarly, multivariate regression demonstrated correlations with executive dysfunction (p=.05, FDR corrected) and apathy (p=.05, FDR corrected). Exploratory analysis demonstrated an interaction wherein the relationship between total WMHs and executive dysfunction and apathy depends on whether the participant was a survivor. The current findings indicate that increased WMH volumes are associated with higher ratings of apathy and executive dysfunction, and that these results are likely unique to cerebellar brain tumor survivors. WMH burden may serve as a useful marker to identify survivors at risk of executive dysfunction or increased apathy.

White matter hyperintensity volumes are related to processing speed in long-term survivors of childhood cerebellar tumors.

PURPOSE: Across several clinical populations, higher white matter hyperintensity (WMH) burden is consistently associated with decreases in cognitive performance, especially processing speed. Research of childhood cancer survivors has not utilized WMH quantification methodology to better understand the impact of WMH burden and its relationship with core cognitive skills. The present study aimed to quantify WMH volumes in a sample of long-term survivors of childhood cerebellar tumor and investigate the relationships with performance on a measure of oral processing speed. To further explore brain-behavior relationships, multivariate sparse canonical correlations was employed to identify WMH areas that predict processing speed performance. METHODS: Thirty-five survivors and 56 healthy controls underwent neuroimaging and completed a measure of oral processing speed. The survivor group was further divided based on treatment (i.e., chemoradiation therapy (n = 20) vs. surgery only (n = 15)) to better understand the impact of treatment. RESULTS: Survivors, and especially those treated with chemoradiation therapy, showed higher total WMH volumes and slower processing speed. Higher total WMH volumes were significantly associated with poorer processing speed (r = - 0.492, p = 0.003). Multivariate brain-behavior relationships revealed that periventricular WMHs were significantly associated with slower processing speed performance (p < 0.05). CONCLUSION: Results exemplify that long-term survivors treated with and without chemoradiation therapy are at increased risk of developing higher WMH volumes compared to healthy peers. In addition, processing speed was robustly shown to be related to periventricular WMHs using an automated neuroimaging pipeline. This methodology to monitor WMH burden has the potential to be implemented efficiently with routine clinical neuroimaging of cancer survivors.

Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions.

Over the past few decades, research has established that the cerebellum is involved in executive functions; however, its specific role remains unclear. There are numerous theories of cerebellar function and numerous cognitive processes falling under the umbrella of executive function, making investigations of the cerebellum's role in executive functioning challenging. In this review, we explored the role of the cerebellum in executive functioning through clinical and cognitive neuroscience frameworks. We reviewed the neuroanatomical systems and theoretical models of cerebellar functions and the multifaceted nature of executive functions. Using attention deficit hyperactivity disorder and cerebellar tumor as clinical developmental models of cerebellar dysfunction, and the functional magnetic resonance imaging literature, we reviewed evidence for cerebellar involvement in specific components of executive function in childhood, adolescence, and adulthood. There is evidence for posterior cerebellar contributions to working memory, planning, inhibition, and flexibility, but the heterogeneous literature that largely was not designed to study the cerebellum makes it difficult to determine specific functions of the cerebellum or cerebellar regions. In addition, while it is clear that cerebellar insult in childhood affects executive function performance later in life, more work is needed to elucidate the mechanisms by which executive dysfunction occurs and its developmental course. The limitations of the current literature are discussed and potential directions for future research are provided.

Associations among diffusion tensor imaging and neurocognitive function in survivors of pediatric brain tumor: A pilot study.

The purpose of this study was to determine associations among neurocognitive outcomes and white matter integrity in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and genu of the corpus callosum (gCC) in survivors of pediatric brain tumor and healthy controls (HCs). Eleven survivors (ages 8-16; >2 years post-treatment) and 14 HCs underwent MRI; diffusion tensor imaging tractography (DSI Studio) was used to assess white matter integrity. Participants completed neuropsychological assessment of overall cognitive ability, executive function, processing speed, divided attention, and memory. As previously reported, survivors performed significantly worse than HCs on measures of overall IQ, working memory, processing speed, and executive function (ps < .01), but not on measures of long-delay memory. Mean fractional anisotropy was significantly lower in survivors than HC in the right IFOF, left UF, and gCC (ps < .05). Correlations with the total sample revealed a number of significant positive associations among white matter tracts and scores on neurocognitive measures. Survivors show deficits on measures of cognitive function and decreased white matter integrity compared to HCs. Results revealed a more general pattern of associations among white matter pathways and neurocognitive outcomes than initially hypothesized. It is possible that survivors with diffuse pathology from treatment effects (i.e., hydrocephalus or posterior fossa syndrome) show more general decreases in cognitive functioning and white matter integrity. Additional research with a larger and more diverse group of survivors is needed to better understand white matter integrity and neurocognitive outcome associations in this population.

Fronto-limbic white matter microstructure, behavior, and emotion regulation in survivors of pediatric brain tumor.

PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.