The VWFA: It\u27s not just for words anymore

Reading is an important but phylogenetically new skill. While neuroimaging studies have identified brain regions used in reading, it is unclear to what extent these regions become specialized for use predominantly in reading vs. other tasks. Over the past several years, our group has published three studies addressing this question, particularly focusing on whether the putative visual word form area (VWFA) is used predominantly in reading, or whether it is used more generally in a number of tasks. Our three studies utilize a range of neuroimaging techniques, including task based fMRI experiments, a seed based resting state functional connectivity (RSFC) experiment, and a network based RSFC experiment. Overall, our studies indicate that the VWFA is not used specifically or even predominantly for reading. Rather the VWFA is a general use region that has processing properties making it particularly useful for reading, though it continues to be used in any task that requires its general processing properties. Our network based RSFC analysis extends this finding to other regions typically thought to be used predominantly for reading. Here, we review these findings and describe how the three studies complement each other. Then, we argue that conceptualizing the VWFA as a brain region with specific processing characteristics rather than a brain region devoted to a specific stimulus class, allows us to better explain the activity seen in this region during a variety of tasks. Having this type of conceptualization not only provides a better understanding of the VWFA but also provides a framework for understanding other brain regions, as it affords an explanation of function that is in keeping with the long history of studying the brain in terms of the type of information processing performed (Posner, 1978)

Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

Considerations for MRI study design and implementation in pediatric and clinical populations

AbstractHuman neuroimaging, specifically magnetic resonance imaging (MRI), is being used with increasing popularity to study brain structure and function in development and disease. When applying these methods to developmental and clinical populations, careful consideration must be taken with regard to study design and implementation. In this article, we discuss two major considerations particularly pertinent to brain research in special populations. First, we discuss considerations for subject selection and characterization, including issues related to comorbid conditions, medication status, and clinical assessment. Second, we discuss methods and considerations for acquisition of adequate, useable MRI data. Given that children and patients may experience anxiety with the scanner environment, preventing participation, and that they have a higher risk of motion artifact, resulting in data loss, successful subject compliance and data acquisition are not trivial tasks. We conclude that, as researchers, we must consider a number of issues when using neuroimaging tools to study children and patients, and we should thoughtfully justify our choices of methods and study design

Studying Brain Organization via Spontaneous fMRI Signal

In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the “resting” brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called “resting state.” This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization

Correlation of CAG repeat length between the maternal and paternal allele of the Huntingtin gene: evidence for assortative mating

Triplet repeats contribute to normal variation in behavioral traits and when expanded, cause brain disorders. While Huntington's Disease is known to be caused by a CAG triplet repeat in the gene Huntingtin, the effect of CAG repeats on brain function below disease threshold has not been studied. The current study shows a significant correlation between the CAG repeat length of the maternal and paternal allele in the Huntingtin gene among healthy subjects, suggesting assortative mating

Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome

BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients. METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven\u27s Progressive Matrices to estimate IQ. RESULTS: Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults. CONCLUSIONS: The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores

Manipulation of length and lexicality localizes the functional neuroanatomy of phonological processing in adult readers

In a previous study of single word reading, regions in the left supramarginal gyrus and left angular gyrus showed positive BOLD activity in children but significantly less activity in adults for high-frequency words. This developmental decrease may reflect decreased reliance on phonological processing for familiar stimuli in adults. Therefore, in the present study, variables thought to influence phonological demand (string length and lexicality) were manipulated. Length and lexicality effects in the brain were explored using both ROI and whole-brain approaches. In the ROI analysis, the supramarginal and angular regions from the previous study were applied to this study. The supramarginal region showed a significant positive effect of length, consistent with a role in phonological processing, whereas the angular region showed only negative deflections from baseline with a strong effect of lexicality and other weaker effects. At the whole-brain level, varying effects of length and lexicality and their interactions were observed in 85 regions throughout the brain. The application of hierarchical clustering analysis to the BOLD time course data derived from these regions revealed seven clusters, with potentially revealing anatomical locations. Of note, a left angular gyrus region was the sole constituent of one cluster. Taken together, these findings in adult readers (1) provide support for a widespread set of brain regions affected by lexical variables, (2) corroborate a role for phonological processing in the left supramarginal gyrus, and (3) do not support a strong role for phonological processing in the left angular gyrus