Inhibitory modulation of speech trajectories: Evidence from a vowel-modified Stroop task.

How does cognitive inhibition influence speaking? The Stroop effect is a classic demonstration of the interference between reading and color naming. We used a novel variant of the Stroop task to measure whether this interference impacts not only the response speed, but also the acoustic properties of speech. Speakers named the color of words in three categories: congruent (e.g., red written in red), color-incongruent (e.g., green written in red), and vowel-incongruent - those with partial phonological overlap with their color (e.g., rid written in red, grain in green, and blow in blue). Our primary aim was to identify any effect of the distractor vowel on the acoustics of the target vowel. Participants were no slower to respond on vowel-incongruent trials, but formant trajectories tended to show a bias away from the distractor vowel, consistent with a phenomenon of acoustic inhibition that increases contrast between confusable alternatives.

Intact procedural memory and impaired auditory statistical learning in adults with dyslexia.

Developmental dyslexia is a reading disorder that is associated with atypical brain function. One neuropsychological theory posits that dyslexia reflects a deficit in the procedural memory system, which supports implicit learning, or the acquisition of knowledge without conscious awareness or intention. This study investigated various forms of procedural learning in adults with dyslexia and typically-reading adults. Adults with dyslexia exhibited typical skill learning on mirror tracing and rotary pursuit tasks that have been well-established as reflecting purely procedural memory and dependent on basal ganglia and cerebellar structures. They also exhibited typical statistical learning for visual material, but impaired statistical learning for auditory material. Auditory statistical learning proficiency correlated positively with single-word reading performance across all participants and within the group with dyslexia, linking a major difficulty in dyslexia with impaired auditory statistical learning. These findings dissociate multiple forms of procedural memory that are intact in dyslexia from a specific impairment in auditory statistical learning that is associated with reading difficulty.

Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

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.

Speech-specific perceptual adaptation deficits in children and adults with dyslexia.

According to several influential theoretical frameworks, phonological deficits in dyslexia result from reduced sensitivity to acoustic cues that are essential for the development of robust phonemic representations. Some accounts suggest that these deficits arise from impairments in rapid auditory adaptation processes that are either speech-specific or domain-general. Here, we examined the specificity of auditory adaptation deficits in dyslexia using a nonlinguistic tone anchoring (adaptation) task and a linguistic selective adaptation task in children and adults with and without dyslexia. Children and adults with dyslexia had elevated tone-frequency discrimination thresholds, but both groups benefited from anchoring to repeated stimuli to the same extent as typical readers. Additionally, although both dyslexia groups had overall reduced accuracy for speech sound identification, only the child group had reduced categorical perception for speech. Across both age groups, individuals with dyslexia had reduced perceptual adaptation to speech. These results highlight broad auditory perceptual deficits across development in individuals with dyslexia for both linguistic and nonlinguistic domains, but speech-specific adaptation deficits. Finally, mediation models in children and adults revealed that the causal pathways from basic perception and adaptation to phonological awareness through speech categorization were not significant. Thus, rather than having causal effects, perceptual deficits may co-occur with the phonological deficits in dyslexia across development. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Electrophysiological correlates of perceptual prediction error are attenuated in dyslexia.

A perceptual adaptation deficit often accompanies reading difficulty in dyslexia, manifesting in poor perceptual learning of consistent stimuli and reduced neurophysiological adaptation to stimulus repetition. However, it is not known how adaptation deficits relate to differences in feedforward or feedback processes in the brain. Here we used electroencephalography (EEG) to interrogate the feedforward and feedback contributions to neural adaptation as adults with and without dyslexia viewed pairs of faces and words in a paradigm that manipulated whether there was a high probability of stimulus repetition versus a high probability of stimulus change. We measured three neural dependent variables: expectation (the difference between prestimulus EEG power with and without the expectation of stimulus repetition), feedforward repetition (the difference between event-related potentials (ERPs) evoked by an expected change and an unexpected repetition), and feedback-mediated prediction error (the difference between ERPs evoked by an unexpected change and an expected repetition). Expectation significantly modulated prestimulus theta- and alpha-band EEG in both groups. Unexpected repetitions of words, but not faces, also led to significant feedforward repetition effects in the ERPs of both groups. However, neural prediction error when an unexpected change occurred instead of an expected repetition was significantly weaker in dyslexia than the control group for both faces and words. These results suggest that the neural and perceptual adaptation deficits observed in dyslexia reflect the failure to effectively integrate perceptual predictions with feedforward sensory processing. In addition to reducing perceptual efficiency, the attenuation of neural prediction error signals would also be deleterious to the wide range of perceptual and procedural learning abilities that are critical for developing accurate and fluent reading skills.

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.

ERP Mismatch Negativity Amplitude and Asymmetry Reflect Phonological and Rapid Automatized Naming Skills in English-Speaking Kindergartners.

The mismatch negativity (MMN), an electrophysiological response to an oddball auditory stimulus, is related to reading ability in many studies. There are conflicting findings regarding exactly how the MMN relates to risk or actual diagnosis of dyslexia/reading impairment, perhaps due to the heterogeneity of abilities in children with reading impairment. In this study, 166 English-speaking kindergarten children oversampled for dyslexia risk completed behavioral assessments and a speech-syllable MMN paradigm. We examined how early and late MMN mean amplitude and laterality were related to two established predictors of reading ability: phonological awareness (PA) and rapid automatized naming (RAN). In bootstrapped group analyses, late MMN amplitude was significantly greater in children with typical PA ability than low PA ability. In contrast, laterality of the early and late MMN was significantly different in children with low versus typical RAN ability. Continuous analyses controlling for child age, non-verbal IQ, and letter and word identification abilities showed the same associations between late MMN amplitude with PA and late MMN laterality with RAN. These findings suggest that amplitude of the MMN may relate to phonological representations and ability to manipulate them, whereas MMN laterality may reflect differences in brain processes that support automaticity needed for reading.

Putative protective neural mechanisms in prereaders with a family history of dyslexia who subsequently develop typical reading skills.

Developmental dyslexia affects 40-60% of children with a familial risk (FHD+) compared to a general prevalence of 5-10%. Despite the increased risk, about half of FHD+ children develop typical reading abilities (FHD+Typical). Yet the underlying neural characteristics of favorable reading outcomes in at-risk children remain unknown. Utilizing a retrospective, longitudinal approach, this study examined whether putative protective neural mechanisms can be observed in FHD+Typical at the prereading stage. Functional and structural brain characteristics were examined in 47 FHD+ prereaders who subsequently developed typical (n = 35) or impaired (n = 12) reading abilities and 34 controls (FHD-Typical). Searchlight-based multivariate pattern analyses identified distinct activation patterns during phonological processing between FHD+Typical and FHD-Typical in right inferior frontal gyrus (RIFG) and left temporo-parietal cortex (LTPC) regions. Follow-up analyses on group-specific classification patterns demonstrated LTPC hypoactivation in FHD+Typical compared to FHD-Typical, suggesting this neural characteristic as an FHD+ phenotype. In contrast, RIFG showed hyperactivation in FHD+Typical than FHD-Typical, and its activation pattern was positively correlated with subsequent reading abilities in FHD+ but not controls (FHD-Typical). RIFG hyperactivation in FHD+Typical was further associated with increased interhemispheric functional and structural connectivity. These results suggest that some protective neural mechanisms are already established in FHD+Typical prereaders supporting their typical reading development.

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.

The relationship between socioeconomic status and white matter microstructure in pre-reading children: A longitudinal investigation.

Reading is a learned skill crucial for educational attainment. Children from families of lower socioeconomic status (SES) tend to have poorer reading performance and this gap widens across years of schooling. Reading relies on the orchestration of multiple neural systems integrated via specific white-matter pathways, but there is limited understanding about whether these pathways relate differentially to reading performance depending on SES background. Kindergarten white-matter FA and second-grade reading outcomes were investigated in an SES-diverse sample of 125 children. The three left-hemisphere white-matter tracts most associated with reading, and their right-hemisphere homologs, were examined: arcuate fasciculus (AF), superior longitudinal fasciculus (SLF), and inferior longitudinal fasciculus (ILF). There was a significant and positive association between SES and fractional anisotropy (FA) in the bilateral ILF in kindergarten. SES moderated the association between kindergarten ILF and second grade reading performance, such that it was positive in lower-SES children, but not significant in higher-SES children. These results have implications for understanding the role of the environment in the development of the neural pathways that support reading.

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.

Native-language N400 and P600 predict dissociable language-learning abilities in adults.

Language learning aptitude during adulthood varies markedly across individuals. An individual's native-language ability has been associated with success in learning a new language as an adult. However, little is known about how native-language processing affects learning success and what neural markers of native-language processing, if any, are related to success in learning. We therefore related variation in electrophysiology during native-language processing to success in learning a novel artificial language. Event-related potentials (ERPs) were recorded while native English speakers judged the acceptability of English sentences prior to learning an artificial language. There was a trend towards a double dissociation between native-language ERPs and their relationships to novel syntax and vocabulary learning. Individuals who exhibited a greater N400 effect when processing English semantics showed better future learning of the artificial language overall. The N400 effect was related to syntax learning via its specific relationship to vocabulary learning. In contrast, the P600 effect size when processing English syntax predicted future syntax learning but not vocabulary learning. These findings show that distinct neural signatures of native-language processing relate to dissociable abilities for learning novel semantic and syntactic information.

Longitudinal stability of pre-reading skill profiles of kindergarten children: implications for early screening and theories of reading.

Research suggests that early identification of developmental dyslexia is important for mitigating the negative effects of dyslexia, including reduced educational attainment and increased socioemotional difficulties. The strongest pre-literacy predictors of dyslexia are rapid automatized naming (RAN), phonological awareness (PA), letter knowledge, and verbal short-term memory. The relationship among these constructs has been debated, and several theories have emerged to explain the unique role of each in reading ability/disability. Furthermore, the stability of identification of risk based on these measures varies widely across studies, due in part to the different cut-offs employed to designate risk. We applied a latent profile analysis technique with a diverse sample of 1215 kindergarten and pre-kindergarten students from 20 schools, to investigate whether PA, RAN, letter knowledge, and verbal short-term memory measures differentiated between homogenous profiles of performance on these measures. Six profiles of performance emerged from the data: average performers, below average performers, high performers, PA risk, RAN risk, and double-deficit risk (both PA and RAN). A latent class regression model was employed to investigate the longitudinal stability of these groups in a representative subset of children (n = 95) nearly two years later, at the end of 1st grade. Profile membership in the spring semester of pre-kindergarten or fall semester of kindergarten was significantly predictive of later reading performance, with the specific patterns of performance on the different constructs remaining stable across the years. There was a higher frequency of PA and RAN deficits in children from lower socioeconomic status (SES) backgrounds. There was no evidence for the IQ-achievement discrepancy criterion traditionally used to diagnose dyslexia. Our results support the feasibility of early identification of dyslexia risk and point to the heterogeneity of risk profiles. These findings carry important implications for improving outcomes for children with dyslexia, based on more targeted interventions.

Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study.

Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here, we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n = 29) and without (FHD-, n = 21) a family history of developmental dyslexia. We further controlled for socioeconomic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHD- compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD- children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models.

Connectivity precedes function in the development of the visual word form area.

What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.

Neurobiology of dyslexia.

Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences before formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia.

Tracking the roots of reading ability: white matter volume and integrity correlate with phonological awareness in prereading and early-reading kindergarten children.

Developmental dyslexia, an unexplained difficulty in learning to read, has been associated with alterations in white matter organization as measured by diffusion-weighted imaging. It is unknown, however, whether these differences in structural connectivity are related to the cause of dyslexia or if they are consequences of reading difficulty (e.g., less reading experience or compensatory brain organization). Here, in 40 kindergartners who had received little or no reading instruction, we examined the relation between behavioral predictors of dyslexia and white matter organization in left arcuate fasciculus, inferior longitudinal fasciculus, and the parietal portion of the superior longitudinal fasciculus using probabilistic tractography. Higher composite phonological awareness scores were significantly and positively correlated with the volume of the arcuate fasciculus, but not with other tracts. Two other behavioral predictors of dyslexia, rapid naming and letter knowledge, did not correlate with volumes or diffusion values in these tracts. The volume and fractional anisotropy of the left arcuate showed a particularly strong positive correlation with a phoneme blending test. Whole-brain regressions of behavioral scores with diffusion measures confirmed the unique relation between phonological awareness and the left arcuate. These findings indicate that the left arcuate fasciculus, which connects anterior and posterior language regions of the human brain and which has been previously associated with reading ability in older individuals, is already smaller and has less integrity in kindergartners who are at risk for dyslexia because of poor phonological awareness. These findings suggest a structural basis of behavioral risk for dyslexia that predates reading instruction.