Alecia C. Vogel

Prediction of Individual Brain Maturity Using fMRI

Connectivity Map of the Brain The growing appreciation that clinically abnormal behaviors in children and adolescents may be influenced or perhaps even initiated by developmental miscues has stoked an interest in mapping normal human brain maturation. Several groups have documented changes in gray and white matter using structural and functional magnetic resonance imaging (fMRI) in cross-sectional and longitudinal studies. Dosenbach et al. (p. 1358) developed an index of resting-state functional connectivity (that is, how tightly neuronal activities in distinct brain regions are correlated while the subject is at rest or even asleep) from analyses of three independent data sets (each based on fMRI scans of 150 to 200 individuals from ages 6 to 35 years old). Long-range connections increased with age and short-range connections decreased, indicating that networks become sparser and sharper with brain maturation. Multivariate pattern analysis of 5-minute brain scans provides a measure of brain maturity. Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals’ brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain’s major functional networks.

Statistical Improvements in Functional Magnetic Resonance Imaging Analyses Produced by Censoring High-Motion Data Points

Subject motion degrades the quality of task functional magnetic resonance imaging (fMRI) data. Here, we test two classes of methods to counteract the effects of motion in task fMRI data: (1) a variety of motion regressions and (2) motion censoring (“motion scrubbing”). In motion regression, various regressors based on realignment estimates were included as nuisance regressors in general linear model (GLM) estimation. In motion censoring, volumes in which head motion exceeded a threshold were withheld from GLM estimation. The effects of each method were explored in several task fMRI data sets and compared using indicators of data quality and signal‐to‐noise ratio. Motion censoring decreased variance in parameter estimates within‐ and across‐subjects, reduced residual error in GLM estimation, and increased the magnitude of statistical effects. Motion censoring performed better than all forms of motion regression and also performed well across a variety of parameter spaces, in GLMs with assumed or unassumed response shapes. We conclude that motion censoring improves the quality of task fMRI data and can be a valuable processing step in studies involving populations with even mild amounts of head movement. Hum Brain Mapp 35:1981–1996, 2014.

Development of the Brain’s Functional Network Architecture

A full understanding of the development of the brain’s functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.

The Putative Visual Word Form Area Is Functionally Connected to the Dorsal Attention Network

The putative visual word form area (pVWFA) is the most consistently activated region in single word reading studies (i.e., Vigneau et al. 2006), yet its function remains a matter of debate. The pVWFA may be predominantly used in reading or it could be a more general visual processor used in reading but also in other visual tasks. Here, resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) is used to characterize the functional relationships of the pVWFA to help adjudicate between these possibilities. rs-fcMRI defines relationships based on correlations in slow fluctuations of blood oxygen level-dependent activity occurring at rest. In this study, rs-fcMRI correlations show little relationship between the pVWFA and reading-related regions but a strong relationship between the pVWFA and dorsal attention regions thought to be related to spatial and feature attention. The rs-fcMRI correlations between the pVWFA and regions of the dorsal attention network increase with age and reading skill, while the correlations between the pVWFA and reading-related regions do not. These results argue the pVWFA is not used predominantly in reading but is a more general visual processor used in other visual tasks, as well as reading.

The VWFA: it's 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).

The Left Occipitotemporal Cortex Does Not Show Preferential Activity for Words

Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high-spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters.

Matching is not naming: A direct comparison of lexical manipulations in explicit and implicit reading tasks

The neurobiological basis of reading is of considerable interest, yet analyzing data from subjects reading words aloud during functional MRI data collection can be difficult. Therefore, many investigators use surrogate tasks such as visual matching or rhyme matching to eliminate the need for spoken output. Use of these tasks has been justified by the presumption of “automatic activation” of reading‐related neural processing when a word is viewed. We have tested the efficacy of using a nonreading task for studying “reading effects” by directly comparing blood oxygen level dependent (BOLD) activity in subjects performing a visual matching task and an item naming task on words, pseudowords (meaningless but legal letter combinations), and nonwords (meaningless and illegal letter combinations). When compared directly, there is significantly more activity during the naming task in “reading‐related” regions such as the inferior frontal gyrus (IFG) and supramarginal gyrus. More importantly, there are differing effects of lexicality in the tasks. A whole‐brain task (matching vs. naming) by string type (word vs. pseudoword vs. nonword) by BOLD timecourse analysis identifies regions showing this three‐way interaction, including the left IFG and left angular gyrus (AG). In the majority of the identified regions (including the left IFG and left AG), there is a string type × timecourse interaction in the naming but not the matching task. These results argue that the processing performed in specific regions is contingent on task, even in reading‐related regions and is thus nonautomatic. Such differences should be taken into consideration when designing studies intended to investigate reading. Hum Brain Mapp 34:2425–2438, 2013.

Neurodevelopmental disorders in children with neurofibromatosis type 1

Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several important neurodevelopmental problems. In this review, we summarize the specific neurodevelopmental problems encountered in the context of NF1. These include impairments in general cognitive function, deficits in specific cognitive domains such as executive function and visuospatial processing and risk for specific learning disorders, impairments in attention and social skills and the overlap with attention‐deficit–hyperactivity disorder and autism spectrum disorder, and the risk of developing other psychiatric conditions including anxiety and depression. Early recognition of these developmental impairments is important for the effective treatment of children with NF1, and further characterization is essential to improve our understanding of how mutations in the NF1 gene create the diversity of clinical neuropsychiatric symptomatology observed in this at‐risk population.