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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 3rd and 4th 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. [ABSTRACT FROM AUTHOR]

Background: Spatial normalization plays an essential role in multi-subject MRI and functional MRI (fMRI) experiments by facilitating a common space in which group analyses are performed. Although many prominent adult templates are available, their use for pediatric data is problematic. Generalized templates for pediatric populations are limited or constructed using older methods that result in less ideal normalization. Objective: The Haskins pediatric templates and atlases aim to provide superior registration and more precise accuracy in labeling of anatomical and functional regions essential for all fMRI studies involving pediatric populations. Materials and methods: The Haskins pediatric templates and atlases were generated with nonlinear methods using structural MRI from 72 children (age range 7–14 years, median 10 years), allowing for a detailed template with corresponding parcellations of labeled atlas regions. The accuracy of these templates and atlases was assessed using multiple metrics of deformation distance and overlap. Results: When comparing the deformation distances from normalizing pediatric data between this template and both the adult templates and other pediatric templates, we found significantly less deformation distance for the Haskins pediatric template (P<0.0001). Further, the correct atlas classification was higher using the Haskins pediatric template in 74% of regions (P<0.0001). Conclusion: The Haskins pediatric template results in more accurate correspondence across subjects because of lower deformation distances. This correspondence also provides better accuracy in atlas locations to benefit structural and functional imaging analyses of pediatric populations. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00247-020-04958-w [ABSTRACT FROM AUTHOR]

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]

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]

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.Neuropsychopharmacology (2007) 32, 2453–2464; doi:10.1038/sj.npp.1301398; published online 21 March 2007 [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]

Rationale. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a potent and selective serotonin neurotoxin whose use is growing among adolescents. Although cognitive deficits among adult MDMA users are well documented, little is known of the cognitive and brain functional sequelae of MDMA use during adolescence. Objective. We tested for evidence of cognitive deficits and changes in brain function in a pilot sample of adolescent MDMA users, who were compared with adolescent non-users of MDMA. Methods. Selective and divided attention and verbal working memory were examined in six adolescent MDMA users and six non-users of MDMA who were similar in age, gender, IQ, and other substance use. Brain function was assessed during performance of the working memory task using functional magnetic resonance imaging (fMRI). Results. MDMA users had significantly prolonged reaction times during tests of selective and divided attention, and failed to deactivate the left hippocampus normally during high verbal working memory load. Conclusions. MDMA use in adolescence may be associated with cognitive impairments and dysfunction of inhibitory circuits within the hippocampus. Further work is urgently needed to delineate the developmental impact and long-term functional and clinical significance of MDMA use during adolescence. [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]