Neurocognitive mechanisms of co‐occurring math difficulties in dyslexia: Differences in executive function and visuospatial processing

Children with dyslexia frequently also struggle with math. However, studies of reading disability (RD) rarely assess math skill, and the neurocognitive mechanisms underlying co-occurring reading and math disability (RD+MD) are not clear. The current study aimed to identify behavioral and neurocognitive factors associated with co-occurring MD among 86 children with RD. Within this sample, 43% had co-occurring RD+MD and 22% demonstrated a possible vulnerability in math, while 35% had no math difficulties (RD-Only). We investigated whether RD-Only and RD+MD students differed behaviorally in their phonological awareness, reading skills, or executive functions, as well as in the brain mechanisms underlying word reading and visuospatial working memory using functional magnetic resonance imaging (fMRI). The RD+MD group did not differ from RD-Only on behavioral or brain measures of phonological awareness related to speech or print. However, the RD+MD group demonstrated significantly worse working memory and processing speed performance than the RD-Only group. The RD+MD group also exhibited reduced brain activations for visuospatial working memory relative to RD-Only. Exploratory brain-behavior correlations along a broad spectrum of math ability revealed that stronger math skills were associated with greater activation in bilateral visual cortex. These converging neuro-behavioral findings suggest that poor executive functions in general, including differences in visuospatial working memory, are specifically associated with co-occurring MD in the context of RD

Cerebellar contributions to rapid semantic processing in reading

National Science Foundation Division of Research on Learning (Grant 1644540)National Institute of Mental Health (Grant F32MH117933

Increased variability of stimulus-driven cortical responses is associated with genetic variability in children with and without dyslexia

Individuals with dyslexia exhibit increased brainstem variability in response to sound. It is unknown as to whether increased variability extends to neocortical regions associated with audition and reading, extends to visual stimuli, and whether increased variability characterizes all children with dyslexia or, instead, a specific subset of children. We evaluated the consistency of stimulus-evoked neural responses in children with (N = 20) or without dyslexia (N = 12) as measured by magnetoencephalography (MEG). Approximately half of the children with dyslexia had significantly higher levels of variability in cortical responses to both auditory and visual stimuli in multiple nodes of the reading network. There was a significant and positive relationship between the number of risk alleles at rs6935076 in the dyslexia-susceptibility gene KIAA0319 and the degree of neural variability in primary auditory cortex across all participants. This gene has been linked with neural variability in rodents and in typical readers. These findings indicate that unstable representations of auditory and visual stimuli in auditory and other reading-related neocortical regions are present in a subset of children with dyslexia and support the link between the gene KIAA0319 and the auditory neural variability across children with or without dyslexia. Keywords: KIAA0319; gene; reading; neural variability; subgroups; mechanismsMGH Institute of Health ProfessionsHalis Foundation for Dyslexia Researc

Categorical perception and influence of attention on neural consistency in response to speech sounds in adults with dyslexia

Developmental dyslexia is a common neurodevelopmental disorder that is associated with alterations in the behavioral and neural processing of speech sounds, but the scope and nature of that association is uncertain. It has been proposed that more variable auditory processing could underlie some of the core deficits in this disorder. In the current study, magnetoencephalography (MEG) data were acquired from adults with and without dyslexia while they passively listened to or actively categorized tokens from a /ba/-/da/ consonant continuum. We observed no significant group difference in active categorical perception of this continuum in either of our two behavioral assessments. During passive listening, adults with dyslexia exhibited neural responses that were as consistent as those of typically reading adults in six cortical regions associated with auditory perception, language, and reading. However, they exhibited significantly less consistency in the left supramarginal gyrus, where greater inconsistency correlated significantly with worse decoding skills in the group with dyslexia. The group difference in the left supramarginal gyrus was evident only when neural data were binned with a high temporal resolution and was only significant during the passive condition. Interestingly, consistency significantly improved in both groups during active categorization versus passive listening. These findings suggest that adults with dyslexia exhibit typical levels of neural consistency in response to speech sounds with the exception of the left supramarginal gyrus and that this consistency increases during active versus passive perception of speech sounds similarly in the two groups.NIH (Grant S10OD021569

Neural Decoding Reveals Concurrent Phonemic and Subphonemic Representations of Speech Across Tasks

Robust and efficient speech perception relies on the interpretation of acoustically variable phoneme realizations, yet prior neuroimaging studies are inconclusive regarding the degree to which subphonemic detail is maintained over time as categorical representations arise. It is also unknown whether this depends on the demands of the listening task. We addressed these questions by using neural decoding to quantify the (dis)similarity of brain response patterns evoked during two different tasks. We recorded magnetoencephalography (MEG) as adult participants heard isolated, randomized tokens from a /ba/-/da/ speech continuum. In the passive task, their attention was diverted. In the active task, they categorized each token as ba or da. We found that linear classifiers successfully decoded ba vs. da perception from the MEG data. Data from the left hemisphere were sufficient to decode the percept early in the trial, while the right hemisphere was necessary but not sufficient for decoding at later time points. We also decoded stimulus representations and found that they were maintained longer in the active task than in the passive task; however, these representations did not pattern more like discrete phonemes when an active categorical response was required. Instead, in both tasks, early phonemic patterns gave way to a representation of stimulus ambiguity that coincided in time with reliable percept decoding. Our results suggest that the categorization process does not require the loss of subphonemic detail, and that the neural representation of isolated speech sounds includes concurrent phonemic and subphonemic information

The Neural Representation of a Repeated Standard Stimulus in Dyslexia

The neural representation of a repeated stimulus is the standard against which a deviant stimulus is measured in the brain, giving rise to the well-known mismatch response. It has been suggested that individuals with dyslexia have poor implicit memory for recently repeated stimuli, such as the train of standards in an oddball paradigm. Here, we examined how the neural representation of a standard emerges over repetitions, asking whether there is less sensitivity to repetition and/or less accrual of “standardness” over successive repetitions in dyslexia. We recorded magnetoencephalography (MEG) as adults with and without dyslexia were passively exposed to speech syllables in a roving-oddball design. We performed time-resolved multivariate decoding of the MEG sensor data to identify the neural signature of standard vs. deviant trials, independent of stimulus differences. This “multivariate mismatch” was equally robust and had a similar time course in the two groups. In both groups, standards generated by as few as two repetitions were distinct from deviants, indicating normal sensitivity to repetition in dyslexia. However, only in the control group did standards become increasingly different from deviants with repetition. These results suggest that many of the mechanisms that give rise to neural adaptation as well as mismatch responses are intact in dyslexia, with the possible exception of a putatively predictive mechanism that successively integrates recent sensory information into feedforward processing.</jats:p

Disrupted left fusiform response to print in beginning kindergartners is associated with subsequent reading

Dyslexia is a common neurobiological disorder in which a child fails to acquire typical word reading skills despite adequate opportunity and intelligence. The visual word form area (VWFA) is a region within the left fusiform gyrus that specializes for print over the course of reading acquisition and is often hypoactivated in individuals with dyslexia. It is currently unknown whether atypicalities in this brain region are already present in kindergarten children who will subsequently develop dyslexia. Here, we measured fMRI activation in response to letters and false fonts in bilateral fusiform gyrus in children with and without risk for dyslexia (defined by family history or low scores on assessments of pre-reading skills, such as phonological awareness). We then followed these children longitudinally through the end of second grade to evaluate whether brain activation patterns in kindergarten were related to second-grade reading outcomes. Compared to typical readers who exhibited no risk factors for reading impairment in kindergarten, there was significant hypoactivation to both letters and false-fonts in the left fusiform gyrus in at-risk children who subsequently developed reading impairment, but not in at-risk children who developed typical reading skills. There were no significant differences in letter- or false-font responses in the right fusiform gyrus among the groups. The finding that hypoactivation to print in the VWFA is present in children who subsequently develop reading impairment even prior to the onset of formal reading instruction suggests that atypical responses to print play an early role in the development of reading impairments such as dyslexia. Keywords: Reading outcomes, Dyslexia, Reading impairment, VWFA, Diagnosi

Early development of letter specialization in left fusiform is associated with better word reading and smaller fusiform face area

A functional region of left fusiform gyrus termed “the visual word form area” (VWFA) develops during reading acquisition to respond more strongly to printed words than to other visual stimuli. Here, we examined responses to letters among 5- and 6-year-old early kindergarten children (N = 48) with little or no school-based reading instruction who varied in their reading ability. We used functional magnetic resonance imaging (fMRI) to measure responses to individual letters, false fonts, and faces in left and right fusiform gyri. We then evaluated whether signal change and size (spatial extent) of letter-sensitive cortex (greater activation for letters versus faces) and letter-specific cortex (greater activation for letters versus false fonts) in these regions related to (a) standardized measures of word-reading ability and (b) signal change and size of face-sensitive cortex (fusiform face area or FFA; greater activation for faces versus letters). Greater letter specificity, but not letter sensitivity, in left fusiform gyrus correlated positively with word reading scores. Across children, in the left fusiform gyrus, greater size of letter-sensitive cortex correlated with lesser size of FFA. These findings are the first to suggest that in beginning readers, development of letter responsivity in left fusiform cortex is associated with both better reading ability and also a reduction of the size of left FFA that may result in right-hemisphere dominance for face perception.Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grant R01HD067312)National Institutes of Health (Grant R01HD067312

Optimizing the production of suspension cells using the G-Rex “M” series

Broader implementation of cell-based therapies has been hindered by the logistics associated with the expansion of clinically relevant cell numbers ex vivo. To overcome this limitation, Wilson Wolf Manufacturing developed the G-Rex, a cell culture flask with a gas-permeable membrane at the base that supports large media volumes without compromising gas exchange. Although this culture platform has recently gained traction with the scientific community due to its superior performance when compared with traditional culture systems, the limits of this technology have yet to be explored. In this study, we investigated multiple variables including optimal seeding density and media volume, as well as maximum cell output per unit of surface area. Additionally, we have identified a novel means of estimating culture growth kinetics. All of these parameters were subsequently integrated into a novel G-Rex “M” series, which can accommodate these optimal conditions. A multicenter study confirmed that this fully optimized cell culture system can reliably produce a 100-fold cell expansion in only 10 days using 1L of medium. The G-Rex M series is linearly scalable and adaptable as a closed system, allowing an easy translation of preclinical protocols into the good manufacturing practice