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We provide an illustration of an application of the elastic net to a large number of common genetic variants in the context of the search for the genetic bases of an endophenotype conceivably related to individual differences in learning. GABA concentration in the occipital cortex, a critical area for reading, was obtained in a group ( n = 76) of children aged 6-10 years. Two extreme groups, high and low, were selected for genotyping with the 650Y Illumina array chip (Ilmn650Y). An elastic net approach was applied to the resulting SNP dataset; 100 SNPs were identified for each chromosome as 'interesting' based on having the highest absolute value coefficients. The analyses highlighted chromosomes 15 and 20, which contained 55 candidate genes. The STRING partner analyses of the associated proteins pointed to a number of related genes, most notably, GABA and NTRK receptors. [ABSTRACT FROM AUTHOR]

Abstract: Prematurely born children are at increased risk for language deficits at school age and beyond, but the neurobiological basis of these findings remains poorly understood. Thirty-one PT adolescents (600–1250g birth weight) and 36 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children-III (WISC-III), the Peabody Picture Vocabulary Test-Revised (PPVT-R), the Comprehensive Test of Phonological Processing (CTOPP) and the Test of Word Reading Efficiency (TOWRE) at 16years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. PT subjects scored significantly lower on all components of the WISC-III (p <0.05) compared to term subjects, but there was no significant difference in PPVT-R scores between the groups. Functional connectivity (fcMRI) between Wernicke''s area (left BA 22) and the right supramarginal gyrus (BA 40) was increased in preterm subjects relative to term controls (p =0.03), and the strength of this connection was inversely related to performance on both the PPVT-R (R 2 =0.553, p =0.002), and the verbal comprehension index (R 2 =0.439, p =0.019). Preterm adolescents engage a dorsal right hemisphere region for language at age 16years. Those with the greatest cognitive deficits demonstrate increasing reliance on this alternate pathway. [Copyright &y& Elsevier]

Using functional magnetic resonance imaging, we investigated multimodal (visual and auditory) semantic and unimodal (visual only) phonological processing in reading disabled (RD) adolescents and non-impaired (NI) control participants. We found reduced activation for RD relative to NI in a number of left-hemisphere reading-related areas across all processing tasks regardless of task type (semantic vs. phonological) or modality (auditory vs. visual modality). Moreover, activation differences in these regions, which included the inferior frontal gyrus, the superior temporal gyrus, and the occipitotemporal region, were largely independent of in-scanner performance in our auditory semantic task. That is, although RD participants and NI participants differed in performance in visually presented conditions, they did not differ significantly in the auditory condition, yet similar patterns of reduced activation were observed in these regions across conditions. These findings indicate a neurobiological marker in RD that is independent of task, modality, or performance. These findings are discussed in the context of current neurobiological models of RD. [ABSTRACT FROM AUTHOR]

Using fMRI, we explored the relationship between phonological awareness (PA), a measure of metaphonological knowledge of the segmental structure of speech, and brain activation patterns during processing of print and speech in young readers from 6 to 10 years of age. Behavioral measures of PA were positively correlated with activation levels for print relative to speech tokens in superior temporal and occipito-temporal regions. Differences between print-elicited activation levels in superior temporal and inferior frontal sites were also correlated with PA measures with the direction of the correlation depending on stimulus type: positive for pronounceable pseudowords and negative for consonant strings. These results support and extend the many indications in the behavioral and neurocognitive literature that PA is a major component of skill in beginning readers and point to a developmental trajectory by which written language engages areas originally shaped by speech for learners on the path toward successful literacy acquisition. [ABSTRACT FROM AUTHOR]

Decades of research have led to several competing theories regarding the neural contributors to impaired reading. But how can we know which theory (or theories) identifies the types of markers that indeed differentiate between individuals with reading disabilities (RD) and their typically developing (TD) peers? To answer this question, we propose a new analytical tool for theory evaluation and comparison, grounded in the Bayesian latent-mixture modeling framework. We start by constructing a series of latent-mixture classification models, each reflecting one existing theoretical claim regarding the neurofunctional markers of RD (highlighting network-level differences in either mean activation, inter-subject heterogeneity, inter-region variability, or connectivity). Then, we run each model on fMRI data alone (i.e., while models are blind to participants' behavioral status), which enables us to interpret the fit between a model's classification of participants and their behavioral (known) RD/TD status as an estimate of its explanatory power. Results from n=127 adolescents and young adults (RD: n=59; TD: n=68) show that models based on network-level differences in mean activation and heterogeneity failed to differentiate between TD and RD individuals. In contrast, classifications based on variability and connectivity were significantly associated with participants' behavioral status. These findings suggest that differences in inter-region variability and connectivity may be better network-level markers of RD than mean activation or heterogeneity (at least in some populations and tasks). More broadly, the results demonstrate the promise of latent-mixture modeling as a theory-driven tool for evaluating different theoretical claims regarding neural contributors to language disorders and other cognitive traits. [ABSTRACT FROM AUTHOR]

Efficient function of neurocircuitry that supports working memory occurs within a narrow range of dopamine neurotransmission. Work in rodents has shown that exposure to nicotine during adolescence leads to nicotine withdrawal emergent alterations in cortical and subcortical dopamine neurotransmission. To test for evidence that the efficiency of neurocircuitry supporting working memory is altered during acute smoking abstinence in adolescent daily tobacco smokers. Fifty-five adolescent daily tobacco smokers were compared with 38 nonsmokers using functional magnetic resonance imaging while subjects performed a verbal working memory task. Smokers were studied during smoking and after 24 h of abstinence from tobacco use. Performance of a task with high working memory load in the context of smoking abstinence was associated with greater activation of components of the verbal working memory neurocircuit, including left ventrolateral prefrontal cortex and left inferior parietal lobe, among smokers relative to nonsmokers. During smoking abstinence, smokers failed to exhibit increases in functional connectivity between components of the working memory neurocircuit with increasing working memory load observed in nonsmoking adolescents and in prior studies of adults. Smoking abstinence in adolescent smokers is associated with reductions in the efficiency of working memory neurocircuitry and alterations in the functional coordination between components of the working memory neurocircuit. These alterations may stem from effects of nicotine exposure on catecholaminergic systems during adolescent development. [ABSTRACT FROM AUTHOR]

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.Neuropsychopharmacology (2006) 31, 1550–1561. doi:10.1038/sj.npp.1300981; published online 7 December 2005 [ABSTRACT FROM AUTHOR]

Parallel cohorts of Hebrew speakers learning English in the U.S., and American-English speakers learning Hebrew in Israel were tracked over the course of two years of immersion in their L2. We utilised a functional MRI semantic judgement task with print and speech tokens, as well as a battery of linguistic and cognitive behavioural measures prior to and after immersion, to track changes in both L1 and L2 processing. fMRI activation for print tokens produced a similar network of activation in both English and Hebrew, irrespective of L1 or L2 status. Significant convergence of print and speech processing was also observed in both languages across a network of left-hemisphere regions joint for both L1 and L2. Despite significant increases in behavioural measures of L2 proficiency, only a few signs of longitudinal change in L2 brain activation were found. In contrast, L1 showed widespread differences in processing across time, suggesting that the neurobiological footprint of reading is dynamic and plastic even in adults, with L2 immersion impacting L1 processing. Print/speech convergence showed little longitudinal change, suggesting that it is a stable marker of the differences in L1 and L2 processing across L2 proficiency. • Cohorts of L2 (Hebrew/English) learners were tracked over two years of immersion. • fMRI scans probed neurological changes in L1 and L2 print and speech processing. • Greater proficiency in L2 led to few longitudinal changes in L2 brain activation. • L1 processing remains plastic in adults and is impacted by L2 immersion. • Print/speech conversion is a longitudinally stable marker of both L1 and L2 reading. [ABSTRACT FROM AUTHOR]

The BDNF gene is a prominent promoter of neuronal development, maturation and plasticity. Its Val66Met polymorphism affects brain morphology and function within several areas and is associated with several cognitive functions and neurodevelopmental disorder susceptibility. Recently, it has been associated with reading, reading-related traits and altered neural activation in reading–related brain regions. However, it remains unknown if the intermediate phenotypes (IPs, such as brain activation and phonological skills) mediate the pathway from gene to reading or reading disability. By conducting a serial multiple mediation model in a sample of 94 children (age 5–13), our findings revealed no direct effects of genotype on reading. Instead, we found that genotype is associated with brain activation in reading-related and more domain general regions which in turn is associated with phonological processing which is associated with reading. These findings suggest that the BDNF -Val66Met polymorphism is related to reading via phonological processing and functional activation. These results support brain imaging data and neurocognitive traits as viable IPs for complex behaviors. [ABSTRACT FROM AUTHOR]

• Reading requires assimilating regularities between print, speech, and meaning. • We quantify early readers' reliance on these regularities during word naming. • Children who rely more on print-speech regularities have better reading skills. • Children who rely more on print-meaning associations are poorer readers. Statistical views of literacy development maintain that proficient reading requires the assimilation of myriad statistical regularities present in the writing system. Indeed, previous studies have tied statistical learning (SL) abilities to reading skills, establishing the existence of a link between the two. However, some issues are currently left unanswered, including questions regarding the underlying bases for these associations as well as the types of statistical regularities actually assimilated by developing readers. Here we present an alternative approach to study the role of SL in literacy development, focusing on individual differences among beginning readers. Instead of using an artificial task to estimate SL abilities, our approach identifies individual differences in children's reliance on statistical regularities as reflected by actual reading behavior. We specifically focus on individuals' reliance on regularities in the mapping between print and speech versus associations between print and meaning in a word naming task. We present data from 399 children, showing that those whose oral naming performance is impacted more by print-speech regularities and less by associations between print and meaning have better reading skills. These findings suggest that a key route by which SL mechanisms impact developing reading abilities is via their role in the assimilation of sub-lexical regularities between printed and spoken language - and more generally, in detecting regularities that are more reliable than others. We discuss the implications of our findings to both SL and reading theories. [ABSTRACT FROM AUTHOR]

Neuroimaging studies of basic achievement skills - reading and arithmetic - often control for the effect of IQ to identify unique neural correlates of each skill. This may underestimate possible effects of common factors between achievement and IQ measures on neuroimaging results. Here, we simultaneously examined achievement (reading and arithmetic) and IQ measures in young adults, aiming to identify MRI correlates of their common factors. Resting-state fMRI (rs-fMRI) data were analyzed using two metrics assessing local intrinsic functional properties; regional homogeneity (ReHo) and fractional amplitude low frequency fluctuation (fALFF), measuring local intrinsic functional connectivity and intrinsic functional activity, respectively. ReHo highlighted the thalamus/pulvinar (a subcortical region implied for selective attention) as a common locus for both achievement skills and IQ. More specifically, the higher the ReHo values, the lower the achievement and IQ scores. For fALFF, the left superior parietal lobule, part of the dorsal attention network, was positively associated with reading and IQ. Collectively, our results highlight attention-related regions, particularly the thalamus/pulvinar as a key region related to individual differences in performance on all the three measures. ReHo in the thalamus/pulvinar may serve as a tool to examine brain mechanisms underlying a comorbidity of reading and arithmetic difficulties, which could co-occur with weakness in general intellectual abilities. [ABSTRACT FROM AUTHOR]

Reading is a learned activity that engages multiple cognitive systems. In a cohort of typical and struggling adult readers we show evidence that successful oral reading of real words is related to gamma-amino-butyric acid (GABA) concentration in the higher-order language system, whereas reading of unfamiliar pseudo-words is not related to GABA in this system. We also demonstrate the capability of resting state functional connectivity (rsFC) combined with GABA measures to predict single real word compared to pseudo-word reading performance. Results show that the strength of rsFC between left fusiform gyrus (L-FG) and higher-order language systems predicts oral reading behavior of real words, irrespective of the local concentration of GABA. On the other hand, pseudo-words, which require grapheme-to-phoneme conversion, are not predicted by the connection between L-FG and higher-order language system. This suggests that L-FG may have a multi-functional role: lexical processing of real words and grapheme-to-phoneme processing of pseudo-words. Additionally, rsFC between L-FG, pre-motor, and putamen areas are positively related to the oral reading of both real and pseudo-words, suggesting that text may be converted into a phoneme sequence for speech initiation and production regardless of whether the stimulus is a real word or pseudo-word. In summary, from a systems neuroscience perspective, we show that: (i) strong rsFC between higher order visual, language, and pre-motor areas can predict and differentiate efficient oral reading of real and pseudo-words. (ii) GABA measures, along with rsFC, help to further differentiate the neural pathways for previously learned real words versus unfamiliar pseudo-words. [ABSTRACT FROM AUTHOR]

Background: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored., Methods: Participants were 3 rd and 4 th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants., Results: DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found., Conclusions: Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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.

This study presents the implementation of a within-subject neural decoder, based on Support Vector Machines, and its application for the classification of distributed patterns of hemodynamic activation, measured with Functional Near Infrared Spectroscopy (fNIRS) on children, in response to meaningful and meaningless auditory stimuli. Classification accuracy nominally exceeds chance level for the majority of the participants, but fails to reach statistical significance. Future work should investigate whether individual differences in classification accuracy may relate to other characteristics of the children, such as their cognitive, speech or reading abilities.

Recent work has suggested that variability in levels of neural activation may be related to behavioral and cognitive performance across a number of domains and may offer information that is not captured by more traditional measures that use the average level of brain activation. We examined the relationship between reading skill in school-aged children and neural activation variability during a functional MRI reading task after taking into account average levels of activity. The reading task involved matching printed and spoken words to pictures of items. Single trial activation estimates were used to calculate the mean and standard deviation of children's responses to print and speech stimuli; multiple regression analyses evaluated the relationship between reading skill and trial-by-trial activation variability. The reliability of observed findings from the discovery sample ( n = 44; ages 8-11; 18 female) was then confirmed in an independent sample of children ( n = 32; ages 8-11; 14 female). Across the two samples, reading skill was positively related to trial-by-trial variability in the activation response to print in the left inferior frontal gyrus pars triangularis. This relationship held even when accounting for mean levels of activation. This finding suggests that intrasubject variability in trial-by-trial fMRI activation responses to printed words accounts for individual differences in human reading ability that are not fully captured by traditional mean levels of brain activity. Furthermore, this positive relationship between trial-by-trial activation variability and reading skill may provide evidence that neural variability plays a beneficial role during early reading development. SIGNIFICANCE STATEMENT Recent work has suggested that neural activation variability, or moment-to-moment changes in the engagement of brain regions, is related to individual differences in behavioral and cognitive performance across multiple domains. However, differences in neural activation variability have not yet been evaluated in relation to reading skill. In the current study, we analyzed data from two independent groups of children who performed an fMRI task involving reading and listening to words. Across both samples, reading skill was positively related to trial-by-trial variability in activation to print stimuli in the left inferior frontal gyrus pars triangularis, even when accounting for the more conventional measure of mean levels of brain activity. This finding suggests that neural variability could be beneficial in developing readers., (Copyright © 2018 the authors 0270-6474/18/382982-09$15.00/0.)

Speech signals contain information of both linguistic content and a talker's voice. Conventionally, linguistic and talker processing are thought to be mediated by distinct neural systems in the left and right hemispheres respectively, but there is growing evidence that linguistic and talker processing interact in many ways. Previous studies suggest that talker-related vocal tract changes are processed integrally with phonetic changes in the bilateral posterior superior temporal gyrus/superior temporal sulcus (STG/STS), because the vocal tract parameter influences the perception of phonetic information. It is yet unclear whether the bilateral STG is also activated by the integral processing of another parameter - pitch, which influences the perception of lexical tone information and is related to talker differences in tone languages. In this study, we conducted separate functional magnetic resonance imaging (fMRI) and event-related potential (ERP) experiments to examine the spatial and temporal loci of interactions of lexical tone and talker-related pitch processing in Cantonese. We found that the STG was activated bilaterally during the processing of talker changes when listeners attended to lexical tone changes in the stimuli and during the processing of lexical tone changes when listeners attended to talker changes, suggesting that lexical tone and talker processing are functionally integrated in the bilateral STG. It extends the previous study, providing evidence for a general neural mechanism of integral phonetic and talker processing in the bilateral STG. The ERP results show interactions of lexical tone and talker processing 500-800ms after auditory word onset (a simultaneous posterior P3b and a frontal negativity). Moreover, there is some asymmetry in the interaction, such that unattended talker changes affect linguistic processing more than vice versa, which may be related to the ambiguity that talker changes cause in speech perception and/or attention bias to talker changes. Our findings have implications for understanding the neural encoding of linguistic and talker information., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Word reading in alphabetic language involves a cortical system with multiple components whose division of labor depends on the transparency of the writing system. To gain insight about the neural division of labor between phonology and semantics subserving word reading in Chinese, a deep non-alphabetic writing system, functional magnetic resonance imaging (fMRI) was used to investigate the effects of phonological and semantic training on the cortical circuitry for oral naming of Chinese characters. In a training study, we examined whether a training task that differentially focused readers' attention on the phonological or semantic properties of a Chinese character changes the patterns of cortical activation that was evoked by that character in a subsequent naming task. Our imaging results corroborate that the cortical regions underlying reading in Chinese largely overlap the left-hemisphere reading system responsible for reading in alphabetic languages, with some cortical regions in the left-hemisphere uniquely recruited for reading in Chinese. However, in contrast to findings from studies of English word naming, we observed considerable overlap in the neural activation patterns associated with phonological and semantic training on naming Chinese characters, which we suggest may reflect a balanced neural division of labor between phonology and semantics in Chinese character reading. The equitable division of labor for Chinese reading might be driven by the special statistical structure of the writing system, which includes equally systematic mappings in the correspondences between written forms and their pronunciations and meanings., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.

We employed brain-behavior analyses to explore the relationship between performance on tasks measuring phonological awareness, pseudoword decoding, and rapid auditory processing (all predictors of reading (dis)ability) and brain organization for print and speech in beginning readers. For print-related activation, we observed a shared set of skill-correlated regions, including left hemisphere temporoparietal and occipitotemporal sites, as well as inferior frontal, visual, visual attention, and subcortical components. For speech-related activation, shared variance among reading skill measures was most prominently correlated with activation in left hemisphere inferior frontal gyrus and precuneus. Implications for brain-based models of literacy acquisition are discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones., (Copyright © 2009 Elsevier Srl. All rights reserved.)

Functional neuroimaging studies indicate that a primary marker of specific reading disability (RD) is reduced activation of left hemisphere (LH) posterior regions during performance of reading tasks. However, the severity of this disruption, and the extent to which these LH systems might be available for reading under any circumstances, is unclear at present. Experiment 1 examined the cortical effects of stimulus manipulations (frequency, imageability, consistency) that have known facilitative effects on reading performance for both nonimpaired (NI) and RD readers. Experiment 2 examined stimulus repetition, another facilitative variable, in an additional sample of adolescent NI and RD readers. For NI readers, factors that made words easier to process were associated with relatively reduced activation. For RD readers, facilitative factors resulted in increased activation in these same reading-related sites, suggesting that the LH reading circuitry in adolescent RD is poorly trained but not wholly disrupted.

Rationale: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence., Objectives: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory., Materials and Methods: Working memory and brain function were assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes), each of whom was studied twice, once after placement of a placebo patch and once after placement of a nicotine patch. Brain function was assessed using functional magnetic resonance imaging while the subjects performed a verbal working memory task., Results: During performance of a task with high verbal working memory load, nicotine administration worsened performance accuracy and reduced the processing efficiency of brain regions that support phonological rehearsal during verbal working memory in carriers of the 957T allele., Conclusions: These findings are consistent with the notion that genetic variation in DRD2 contributes to individual variation in a range of behavioral and brain responses to nicotine in humans.

fMRI was used to investigate the separate influences of orthographic, phonological, and semantic processing on the ability to learn new words and the cortical circuitry recruited to subsequently read those words. In a behavioral session, subjects acquired familiarity for three sets of pseudowords, attending to orthographic, phonological, or (learned) semantic features. Transfer effects were measured in an event-related fMRI session as the subjects named trained pseudowords, untrained pseudowords, and real words. Behaviorally, phonological and semantic training resulted in better learning than did orthographic training. Neurobiologically, orthographic training did not modulate activation in the main reading regions. Phonological and semantic training yielded equivalent behavioral facilitation but distinct functional activation patterns, suggesting that the learning resulting from these two training conditions was driven by different underlying processes. The findings indicate that the putative ventral visual word form area is sensitive to the phonological structure of words, with phonologically analytic processing contributing to the specialization of this region.