Faculty Bibliography

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 +/- 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.

Valproate is the best choice drug for a variety of medical conditions. As with any other drug, it has adverse effects, and it is important to emphasize the possibility of those adverse effects to prevent complications. We present the case history of a 44-year-old male with valproate-induced hyperammonemic encephalopathy, despite having normal liver function tests. This case includes a detailed literature review of this rare adverse event. In the light of this case report, we illustrate the importance of checking ammonia levels in all psychiatric patients receiving valproate as a treatment who present with new onset neurological symptoms or altered mental status.

PURPOSE OF REVIEW/OBJECTIVE:Imaging research has sought to uncover brain structure, function, and metabolism in women with postpartum depression (PPD) as little is known about its underlying pathophysiology. This review discusses the imaging modalities used to date to evaluate postpartum depression and highlights recent findings. RECENT FINDINGS/RESULTS:Altered functional connectivity and activity changes in brain areas implicated in executive functioning and emotion and reward processing have been identified in PPD. Metabolism changes involving monoamine oxidase A, gamma-aminobutyric acid, glutamate, serotonin, and dopamine have additionally been reported. To date, no studies have evaluated gray matter morphometry, voxel-based morphometry, surface area, cortical thickness, or white matter tract integrity in PPD. Recent imaging studies report changes in functional connectivity and metabolism in women with PPD vs. healthy comparison women. Future research is needed to extend these findings as they have important implications for the prevention and treatment of postpartum mood disorders.

Meta-analysis of neuroimaging results has proven to be a popular and valuable method to study human brain functions. A number of studies have used meta-analysis to parcellate distinct brain regions. A popular way to perform meta-analysis is typically based on the reported activation coordinates from a number of published papers. However, in addition to the coordinates associated with the different brain regions, the text itself contains considerably amount of additional information. This textual information has been largely ignored in meta-analyses where it may be useful for simultaneously parcellating brain regions and studying their characteristics. By leveraging recent advances in document clustering techniques, we introduce an approach to parcellate the brain into meaningful regions primarily based on the text features present in a document from a large number of studies. This new method is called MAPBOT (Meta-Analytic Parcellation Based On Text). Here, we first describe how the method works and then the application case of understanding the sub-divisions of the thalamus. The thalamus was chosen because of the substantial body of research that has been reported studying this functional and structural structure for both healthy and clinical populations. However, MAPBOT is a general-purpose method that is applicable to parcellating any region(s) of the brain. The present study demonstrates the powerful utility of using text information from neuroimaging studies to parcellate brain regions.

Naturalistic viewing paradigms such as movies have been shown to reduce participant head motion and improve arousal during fMRI scanning relative to task-free rest, and have been used to study both functional connectivity and stimulus-evoked BOLD-signal changes. These task-based hemodynamic changes are synchronized across subjects and involve large areas of the cortex, and it is unclear whether individual differences in functional connectivity are enhanced or diminished under such naturalistic conditions. This work first aims to characterize variability in BOLD-signal based functional connectivity (FC) across 2 distinct movie conditions and eyes-open rest (n=31 healthy adults, 2 scan sessions each). We found that movies have higher within- and between-subject correlations in cluster-wise FC relative to rest. The anatomical distribution of inter-individual variability was similar across conditions, with higher variability occurring at the lateral prefrontal lobes and temporoparietal junctions. Second, we used an unsupervised test-retest matching algorithm that identifies individual subjects from within a group based on FC patterns, quantifying the accuracy of the algorithm across the three conditions. The movies and resting state all enabled identification of individual subjects based on FC matrices, with accuracies between 61 and 100%. Overall, pairings involving movies outperformed rest, and the social, faster-paced movie attained 100% accuracy. When the parcellation resolution, scan duration, and number of edges used were increased, accuracies improved across conditions, and the pattern of movies>rest was preserved. These results suggest that using dynamic stimuli such as movies enhances the detection of FC patterns that are unique at the individual level.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. METHODS: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. RESULTS: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. CONCLUSIONS: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.

OBJECTIVE:To test explanations for the underrecognition of female ADHD by examining differences in adult ratings of boys and girls matched for levels of directly observed ADHD behaviors. METHOD/METHODS:In a secondary analysis of a population-based sample, 3- to 4-year-olds ( n = 153, 79 male) and 8- to 9-year-olds ( n = 144, 75 male) were grouped according to levels of directly observed ADHD behaviors (low/moderate/high). Groups were then compared with parent/teacher ADHD ratings. RESULTS:There were no sex differences in levels of directly observed ADHD behaviors within groups. For preschoolers, parents' ratings of males, but not females, significantly increased across groups-mirroring levels of observed behaviors. For older children, both parent and teacher mean ratings were significantly higher for males than females across groups. CONCLUSION/CONCLUSIONS:Identified differences in adult ratings of males and females matched for directly observed behaviors may contribute to understanding the substantial ADHD underrecognition in females.

We examined global and local visual processing in autism spectrum disorder (ASD) via a match-to-sample task using Kanizsa illusory contours (KIC). School-aged children with ASD (n = 28) and age-matched typically developing controls (n = 22; 7-13 years) performed a sequential match-to-sample between a solid shape (sample) and two illusory alternatives. We tracked eye gaze and behavioral performance in two task conditions: one with and one without local interference from background noise elements. While analyses revealed lower accuracy and longer reaction time in ASD in the condition with local interference only, eye tracking robustly captured ASD-related global atypicalities across both conditions. Specifically, relative to controls, children with ASD showed decreased fixations to KIC centers, indicating reduced global perception. Notably, they did not differ from controls in regard to fixations to local elements or touch response location. These results indicate impaired global perception in the absence of heightened local processing in ASD. They also underscore the utility of eye-tracking measures as objective indices of global/local visual processing strategies in ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.