Not all reading disabilities are dyslexia: distinct neurobiology of specific comprehension deficits.
ABSTRACT: Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder.
Project description:Central alexia (CA) is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from poststroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal gyrus (IFG) region to the left occipital (OCC) region. We aimed to identify whether iReadMore therapy was effective through a similar mechanism in patients with CA. Participants with chronic poststroke CA (n = 23) completed 35 h of iReadMore training over 4 weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal, and IFG regions was examined using event-related magnetoencephalography. The training-related modulation in effective connectivity between regions was modeled at the group level with dynamic causal modeling. iReadMore training improved participants' reading accuracy by an average of 8.4% (range, -2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggest that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract representations, to improve word-reading accuracy.SIGNIFICANCE STATEMENT This is the first study to conduct a network-level analysis of therapy effects in participants with poststroke central alexia. When patients trained with iReadMore (a multimodal, behavioral, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in patients with CA iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence-level therapy.
Project description:This study tested the efficacy of audio-visual reading training in nine patients with pure alexia, an acquired reading disorder caused by damage to the left ventral occipitotemporal cortex. As well as testing the therapy's impact on reading speed, we investigated the functional reorganization underlying therapy-induced behavioural changes using magnetoencephalography. Reading ability was tested twice before training (t1 and t2) and twice after completion of the 6-week training period (t3 and t4). At t3 there was a significant improvement in word reading speed and reduction of the word length effect for trained words only. Magnetoencephalography at t3 demonstrated significant differences in reading network connectivity for trained and untrained words. The training effects were supported by increased bidirectional connectivity between the left occipital and ventral occipitotemporal perilesional cortex, and increased feedback connectivity from the left inferior frontal gyrus. Conversely, connection strengths between right hemisphere regions became weaker after training.
Project description:The distinction between letter strings that form words and those that look and sound plausible but are not meaningful is a basic one. Decades of functional neuroimaging experiments have used this distinction to isolate the neural basis of lexical (word level) semantics, associated with areas such as the middle temporal, angular, and posterior cingulate gyri that overlap the default mode network. In two fMRI experiments, a different set of findings emerged when word stimuli were used that were less familiar (measured by word frequency) than those typically used. Instead of activating default mode network areas often associated with semantic processing, words activated task-positive areas such as the inferior pFC and SMA, along with multifunctional ventral occipitotemporal cortices related to reading, whereas nonwords activated default mode areas previously associated with semantics. Effective connectivity analyses of fMRI data on less familiar words showed activation driven by task-positive and multifunctional reading-related areas, whereas highly familiar words showed bottom-up activation flow from occipitotemporal cortex. These findings suggest that functional neuroimaging correlates of semantic processing are less stable than previously assumed, with factors such as word frequency influencing the balance between task-positive, reading-related, and default mode networks. More generally, this suggests that results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.
Project description:Specific reading comprehension deficit (SRCD) affects up to 10 % of all children. SRCD is distinct from dyslexia (DYS) in that individuals with SRCD show poor comprehension despite adequate decoding skills. Despite its prevalence and considerable behavioral research, there is not yet a unified cognitive profile of SRCD. While its neuroanatomical basis is unknown, SRCD could be anomalous in regions subserving their commonly reported cognitive weaknesses in semantic processing or executive function. Here we investigated, for the first time, patterns of gray matter volume difference in SRCD as compared to DYS and typical developing (TD) adolescent readers (N?=?41). A linear support vector machine algorithm was applied to whole brain gray matter volumes generated through voxel-based morphometry. As expected, DYS differed significantly from TD in a pattern that included features from left fusiform and supramarginal gyri (DYS vs. TD: 80.0 %, p?<?0.01). SRCD was well differentiated not only from TD (92.5 %, p?<?0.001) but also from DYS (88.0 %, p?<?0.001). Of particular interest were findings of reduced gray matter volume in right frontal areas that were also supported by univariate analysis. These areas are thought to subserve executive processes relevant for reading, such as monitoring and manipulating mental representations. Thus, preliminary analyses suggest that SRCD readers possess a distinct neural profile compared to both TD and DYS readers and that these differences might be linked to domain-general abilities. This work provides a foundation for further investigation into variants of reading disability beyond DYS.
Project description:Functional connectivity analyses of functional magnetic resonance imaging data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which might result in mixing distinct activation time-courses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia.Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers.Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus.Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words on the basis of their visual properties, whereas DYS readers recruit altered reading circuits and rely on laborious phonology-based "sounding out" strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading.
Project description:Studies with monolingual adults have identified successive stages occurring in different brain regions for processing single written words. We combined magnetoencephalography and magnetic resonance imaging to compare these stages between the first (L1) and second (L2) languages in bilingual adults. L1 words in a size judgment task evoked a typical left-lateralized sequence of activity first in ventral occipitotemporal cortex (VOT: previously associated with visual word-form encoding) and then ventral frontotemporal regions (associated with lexico-semantic processing). Compared to L1, words in L2 activated right VOT more strongly from approximately 135 ms; this activation was attenuated when words became highly familiar with repetition. At approximately 400 ms, L2 responses were generally later than L1, more bilateral, and included the same lateral occipitotemporal areas as were activated by pictures. We propose that acquiring a language involves the recruitment of right hemisphere and posterior visual areas that are not necessary once fluency is achieved.
Project description:Different cortical regions within the ventral occipitotemporal junction have been reported to show preferential responses to particular objects. Thus, it is argued that there is evidence for a left-lateralized visual word form area and a right-lateralized fusiform face area, but the unique specialization of these areas remains controversial. Words are characterized by greater power in the high spatial frequency (SF) range, whereas faces comprise a broader range of high and low frequencies. We investigated how these high-order visual association areas respond to simple sine-wave gratings that varied in SF. Using functional magnetic resonance imaging, we demonstrated lateralization of activity that was concordant with the low-level visual property of words and faces; left occipitotemporal cortex is more strongly activated by high than by low SF gratings, whereas the right occipitotemporal cortex responded more to low than high spatial frequencies. Therefore, the SF of a visual stimulus may bias the lateralization of processing irrespective of its higher order properties.
Project description:Theories of reading have posited the existence of a neural representation coding for whole real words (i.e., an orthographic lexicon), but experimental support for such a representation has proved elusive. Using fMRI rapid adaptation techniques, we provide evidence that the human left ventral occipitotemporal cortex (specifically the "visual word form area," VWFA) contains a representation based on neurons highly selective for individual real words, in contrast to current theories that posit a sublexical representation in the VWFA.
Project description:Individuals with autism show difficulties in using sentence context to identify the correct meaning of ambiguous words, such as homonyms. In this study, the brain basis of sentence context effects on word understanding during reading was examined in autism spectrum disorder (ASD) and typical development (TD) using magnetoencephalography. The correlates of a history of developmental language delay in ASD were also investigated. Event related field responses at early (150 ms after the onset of a final word) and N400 latencies are reported for three different types of sentence final words: dominant homonyms, subordinate homonyms, and unambiguous words. Clear evidence for semantic access was found at both early and conventional N400 latencies in both TD participants and individuals with ASD with no history of language delay. By contrast, modulation of evoked activity related to semantic access was weak and not significant at early latencies in individuals with ASD with a history of language delay. The reduced sensitivity to semantic context in individuals with ASD and language delay was accompanied by strong right hemisphere lateralization at early and N400 latencies; such strong activity was not observed in TD individuals and individuals with ASD without a history of language delay at either latency. These results provide new evidence and support for differential neural mechanisms underlying semantic processing in ASD, and indicate that delayed language acquisition in ASD is associated with different lateralization and processing of language.
Project description:Developmental dyslexia is frequently associated with atypical brain structure and function within regions of the left hemisphere reading network. To date, few studies have employed surface-based techniques to evaluate cortical thickness and local gyrification in dyslexia. Of the existing cortical thickness studies in children, many are limited by small sample size, variability in dyslexia identification, and the recruitment of prereaders who may or may not develop reading impairment. Further, no known study has assessed local gyrification index (LGI) in dyslexia, which may serve as a sensitive indicator of atypical neurodevelopment. In this study, children with dyslexia (n = 31) and typically decoding peers (n = 45) underwent structural magnetic resonance imaging to assess whole-brain vertex-wise cortical thickness and LGI. Children with dyslexia demonstrated reduced cortical thickness compared with controls within previously identified reading areas including bilateral occipitotemporal and occipitoparietal regions. Compared with controls, children with dyslexia also showed increased gyrification in left occipitotemporal and right superior frontal cortices. The convergence of thinner and more gyrified cortex within the left occipitotemporal region among children with dyslexia may reflect its early temporal role in processing word forms, and highlights the importance of the ventral stream for successful word reading.