Stephen J. Frost

Functional neuroimaging studies of reading and reading disability (developmental dyslexia)

Converging evidence from a number of neuroimaging studies, including our own, suggest that fluent word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system is functionally disrupted in developmental dyslexia. Reading disabled readers, relative to nonimpaired readers, demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers the dorsal circuit predominates at first, and is associated with analytic processing necessary for learning to integrate orthographic features with phonological and lexical-semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word identification system which underlies fluent word recognition in skilled readers.

Neurobiological studies of reading and reading disability

UNLABELLEDnEvidence from neuroimaging studies, including our own, suggest that skilled word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system appears to be functionally disrupted in developmental dyslexia. Relative to nonimpaired readers, reading-disabled individuals demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers, the dorsal circuit predominates at first, and in conjunction with premotor systems, is associated with analytic processing necessary for learning to integrate orthographic with phonological and lexical semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word form system, which underlies fluency in word recognition.nnnLEARNING OUTCOMESnAs a result of this activity, (1) the participant will learn about a model of lexical processing involving specific cortical regions. (2) The participant will learn about evidence which supports the theory that two dorsal LH systems may be disrupted in developmental dyslexia. (3) The participant will learn that individuals with reading impairment may rely on other regions of the brain to compensate for the disruption of posterior function.

Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Gender-Specific Effects of Prenatal and Adolescent Exposure to Tobacco Smoke on Auditory and Visual Attention

Prenatal exposure to active maternal tobacco smoking elevates risk of cognitive and auditory processing deficits, and of smoking in offspring. Recent preclinical work has demonstrated a sex-specific pattern of reduction in cortical cholinergic markers following prenatal, adolescent, or combined prenatal and adolescent exposure to nicotine, the primary psychoactive component of tobacco smoke. Given the importance of cortical cholinergic neurotransmission to attentional function, we examined auditory and visual selective and divided attention in 181 male and female adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Groups did not differ in age, educational attainment, symptoms of inattention, or years of parent education. A subset of 63 subjects also underwent functional magnetic resonance imaging while performing an auditory and visual selective and divided attention task. Among females, exposure to tobacco smoke during prenatal or adolescent development was associated with reductions in auditory and visual attention performance accuracy that were greatest in female smokers with prenatal exposure (combined exposure). Among males, combined exposure was associated with marked deficits in auditory attention, suggesting greater vulnerability of neurocircuitry supporting auditory attention to insult stemming from developmental exposure to tobacco smoke in males. Activation of brain regions that support auditory attention was greater in adolescents with prenatal or adolescent exposure to tobacco smoke relative to adolescents with neither prenatal nor adolescent exposure to tobacco smoke. These findings extend earlier preclinical work and suggest that, in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention, with concomitant alterations in the efficiency of neurocircuitry supporting auditory attention.

During Visual Word Recognition, Phonology Is Accessed within 100 ms and May Be Mediated by a Speech Production Code: Evidence from Magnetoencephalography

Debate surrounds the precise cortical location and timing of access to phonological information during visual word recognition. Therefore, using whole-head magnetoencephalography (MEG), we investigated the spatiotemporal pattern of brain responses induced by a masked pseudohomophone priming task. Twenty healthy adults read target words that were preceded by one of three kinds of nonword prime: pseudohomophones (e.g., brein–BRAIN), where four of five letters are shared between prime and target, and the pronunciation is the same; matched orthographic controls (e.g., broin–BRAIN), where the same four of five letters are shared between prime and target but pronunciation differs; and unrelated controls (e.g., lopus–BRAIN), where neither letters nor pronunciation are shared between prime and target. All three priming conditions induced activation in the pars opercularis of the left inferior frontal gyrus (IFGpo) and the left precentral gyrus (PCG) within 100 ms of target word onset. However, for the critical comparison that reveals a processing difference specific to phonology, we found that the induced pseudohomophone priming response was significantly stronger than the orthographic priming response in left IFG/PCG at ∼100 ms. This spatiotemporal concurrence demonstrates early phonological influences during visual word recognition and is consistent with phonological access being mediated by a speech production code.

Neuroimaging Studies of Reading Development and Reading Disability

Converging evidence from a number of neuroimaging studies, including our own, suggest that fluent word identification in reading is related to the functional integrity of two left hemisphere posterior systems: a temporo-parietal system and a ventral occipito-temporal system. These posterior systems are functionally disrupted in developmental dyslexia. Reading disabled, relative to nonimpaired, readers demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers the temporo-parietal system predominates at first, and is associated with aspects of processing critical in learning to integrate orthography with phonological and lexical-semantic features of printed words. The occipito-temporal system, by contrast, constitutes a fast, late-developing, word-identification system that underlies fluent word recognition in skilled readers.

Universal brain signature of proficient reading: Evidence from four contrasting languages

Significance Using functional MRI, we examined reading and speech perception in four highly contrasting languages: Spanish, English, Hebrew, and Chinese. With three complementary analytic approaches, we demonstrate that in spite of striking dissimilarities among writing systems, successful literacy acquisition results in a convergence of the speech and orthographic processing systems onto a common network of neural structures. These findings have the major theoretical implication that the reading network has evolved to be universally constrained by the organization of the brain network underlying speech. We propose and test a theoretical perspective in which a universal hallmark of successful literacy acquisition is the convergence of the speech and orthographic processing systems onto a common network of neural structures, regardless of how spoken words are represented orthographically in a writing system. During functional MRI, skilled adult readers of four distinct and highly contrasting languages, Spanish, English, Hebrew, and Chinese, performed an identical semantic categorization task to spoken and written words. Results from three complementary analytic approaches demonstrate limited language variation, with speech–print convergence emerging as a common brain signature of reading proficiency across the wide spectrum of selected languages, whether their writing system is alphabetic or logographic, whether it is opaque or transparent, and regardless of the phonological and morphological structure it represents.

Identity priming in English is compromised by phonological ambiguity.

If it takes longer to achieve a single phonological representation for inconsistent words (e.g., BOWL) than for consistent words (e.g., BENT), and if phonological coherence is pivotal to visual word recognition, then identity priming should depend on consistency. This hypothesis was evaluated in naming and lexical decision within a 4-field presentation sequence of mask-prime-mask-target. The prime-target stimulus onset asynchrony (SOA) was either 114 or 244 ms (with prime durations, respectively, of 43 and 129 ms). Four experiments compared identity primes such as BOWL and BENT, which were equated, on average, for total number of friendly and unfriendly neighbors, bigram frequency, and number of 1-letter-different neighbors. In both tasks, BENT primed itself better than BOWL primed itself, with the difference being larger at the shorter SOA. Word processing is constrained primarily by the rate of achieving a coherent phonological code.

The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children

Understanding how genes impact the brain’s functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children’s (age 6–10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading–related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

Neurochemistry Predicts Convergence of Written and Spoken Language: A Proton Magnetic Resonance Spectroscopy Study of Cross-Modal Language Integration

Recent studies have provided evidence of associations between neurochemistry and reading (dis)ability (Pugh et al., 2014). Based on a long history of studies indicating that fluent reading entails the automatic convergence of the written and spoken forms of language and our recently proposed Neural Noise Hypothesis (Hancock et al., 2017), we hypothesized that individual differences in cross-modal integration would mediate, at least partially, the relationship between neurochemical concentrations and reading. Cross-modal integration was measured in 231 children using a two-alternative forced choice cross-modal matching task with three language conditions (letters, words, and pseudowords) and two levels of difficulty within each language condition. Neurometabolite concentrations of Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl-aspartate (NAA) were then measured in a subset of this sample (n = 70) with Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model revealed that the effect of cross-modal word matching mediated the relationship between increased Glu (which has been proposed to be an index of neural noise) and poorer reading ability. In addition, the effect of cross-modal word matching fully mediated a relationship between increased Cho and poorer reading ability. Multilevel mixed effects models confirmed that lower Cho predicted faster cross-modal matching reaction time, specifically in the hard word condition. These Cho findings are consistent with previous work in both adults and children showing a negative association between Cho and reading ability. We also found two novel neurochemical relationships. Specifically, lower GABA and higher NAA predicted faster cross-modal matching reaction times. We interpret these results within a biochemical framework in which the ability of neurochemistry to predict reading ability may at least partially be explained by cross-modal integration.