Cortical Signatures of Dyslexia and Remediation: An Intrinsic Functional Connectivity Approach

et al. (2013) Cortical Signatures of Dyslexia and Remediation: An Intrinsic Functional Connectivity Approach. PLoS ONE 8(2): e55454. doi:10.1371/journal.pone.0055454 Cortical Signatures of Dyslexia and Remediation: An Intrinsic Functional Connectivity Approach Maki S. Koyama 0 Adriana Di Martino 0 Clare Kelly 0 Devika R. Jutagir 0 Jessica Sunshine 0 Susan J. Schwartz 0 Francisco X. Castellanos 0 Michael P. Milham 0 Nanyin Zhang, University of Massachusetts Medical School, United States of America 0 1 Rutgers University Center for Molecular and Behavioral Neuroscience, Newark, New Jersey, United States of America, 2 Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center, NYU Langone Medical Center , New York , New York, United States of America, 3 Center for the Developing Brain, Child Mind Institute , New York , New York, United States of America, 4 Nathan Kline Institute for Psychiatric Research , Orangeburg, New York , United States of America This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N = 44, age range = 7-15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network - left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation. - Funding: This study was supported by grants from NIMH [R01MH081218, K23MH087770], the Stavros Niarchos Foundation, and the Leon Levy Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Although the phonological deficit hypothesis (e.g., [12]) is the dominant explanatory theory of developmental dyslexia (a reading disorder), impaired phonological processing alone cannot explain the entirety of clinical symptomatology in the disorder. The majority of individuals with dyslexia suffer from multiple deficits in addition to or independent of phonological deficits [37]. Beyond abnormalities in phonological processing systems, emerging models of dyslexia highlight the potential contributions of dysfunction within systems supporting visual perceptual processing [8], auditory perceptual processing [911], rapid naming [12], and attention control [1315]. In recent years, speculation has increased regarding cerebellar dysfunction in dyslexia [1617]. Yet, with few exceptions [1820], imaging studies of dyslexia have primarily focused on phonological deficits. To help individuals with dyslexia improve literacy performance, substantial remediation efforts have been made, such as those targeting phonological deficits. These efforts have generally resulted in successful behavioral remediation (For review, see [21]). Recent task-based fMRI studies, using mainly phonological tasks, provide evidence of cortical activation changes associated with such behavioral changes (i.e., differences between before and after intervention) in individuals with dyslexia. Broadly, two cortical patterns appear to characterize behavioral remediation: 1) normalized (e.g., increased) activity detected in the known left hemisphere reading network (e.g., left temporoparietal and frontal regions) and 2) compensatory activity detected outside known reading networks (e.g., in right frontal regions) [2226]. The goals of the present work are twofold. First, we aimed to conduct a broader examination of the cortical signatures of dyslexia by employing task-independent resting-state fMRI (RfMRI). While task-based fMRI is of undoubted value, R-fMRI enables bypassing some of the limitations inherent to task-based developmental fMRI studies on reading and dyslexia (e.g., difficulties in developing reading tasks that can be equivocally performed by children in different age/grade groups). Second, we sought to obtain preliminary insights into the cortical signatures of behavioral remediation for reading and spelling deficits in individuals with dyslexia, using an observational, cross-sectional design. Specifically, we recruited individuals with documented evidence of a previous diagnosis of dyslexia, irrespective of the presence of prior remediation efforts or the current level of literacy competence. Consequently, participants varied substantially in literacy profiles, with some continuing to exhibit deficient reading and spelling, whereas others had apparently remediated reading difficulties and, in some cases, spelling deficiencies as well. To investigate the cortical signatures of this well-documented heterogeneity in dyslexia outcomes [2728], we subdivided participants with a previous diagnosis of dyslexia into three groups: (a) children with current literacy deficits (no remediation), (b) children who remediated their reading deficits (partial remediation), and (c) children who remediated both reading and spelling deficits (full remediation). Primary analyses focused on the examination of intrinsic functional connectivity (iFC) [29] in the aforementioned three dyslexia groups (i.e., no remediation, partial remediation, full remediation) and a matched typically developing comparison (TDC) group. Intrinsic functional connectivity is detected by exa (...truncated)