Self-regulation of visual word form area activation with real-time fMRI neurofeedback.

The Visual Word Form Area (VWFA) is a key region of the brain's reading network and its activation has been shown to be strongly associated with reading skills. Here, for the first time, we investigated whether voluntary regulation of VWFA activation is feasible using real-time fMRI neurofeedback. 40 adults with typical reading skills were instructed to either upregulate (UP group, N = 20) or downregulate (DOWN group, N = 20) their own VWFA activation during six neurofeedback training runs. The VWFA target region was individually defined based on a functional localizer task. Before and after training, also regulation runs without feedback ("no-feedback runs") were performed. When comparing the two groups, we found stronger activation across the reading network for the UP than the DOWN group. Further, activation in the VWFA was significantly stronger in the UP group than the DOWN group. Crucially, we observed a significant interaction of group and time (pre, post) for the no-feedback runs: The two groups did not differ significantly in their VWFA activation before neurofeedback training, but the UP group showed significantly stronger activation than the DOWN group after neurofeedback training. Our results indicate that upregulation of VWFA activation is feasible and that, once learned, successful upregulation can even be performed in the absence of feedback. These results are a crucial first step toward the development of a potential therapeutic support to improve reading skills in individuals with reading impairments.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter-speech sound learning in prereaders.

During reading acquisition, neural reorganization of the human brain facilitates the integration of letters and speech sounds, which enables successful reading. Neuroimaging and behavioural studies have established that impaired audiovisual integration of letters and speech sounds is a core deficit in individuals with developmental dyslexia. This longitudinal study aimed to identify neural and behavioural markers of audiovisual integration that are related to future reading fluency. We simulated the first step of reading acquisition by performing artificial-letter training with prereading children at risk for dyslexia. Multiple logistic regressions revealed that our training provides new precursors of reading fluency at the beginning of reading acquisition. In addition, an event-related potential around 400 ms and functional magnetic resonance imaging activation patterns in the left planum temporale to audiovisual correspondences improved cross-validated prediction of future poor readers. Finally, an exploratory analysis combining simultaneously acquired electroencephalography and hemodynamic data suggested that modulation of temporoparietal brain regions depended on future reading skills. The multimodal approach demonstrates neural adaptations to audiovisual integration in the developing brain that are related to reading outcome. Despite potential limitations arising from the restricted sample size, our results may have promising implications both for identifying poor-reading children and for monitoring early interventions.

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis.

OBJECTIVE: Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide. METHOD: T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. RESULTS: The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. CONCLUSIONS: The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.

Neural initialization of audiovisual integration in prereaders at varying risk for developmental dyslexia.

Learning letter-speech sound correspondences is a major step in reading acquisition and is severely impaired in children with dyslexia. Up to now, it remains largely unknown how quickly neural networks adopt specific functions during audiovisual integration of linguistic information when prereading children learn letter-speech sound correspondences. Here, we simulated the process of learning letter-speech sound correspondences in 20 prereading children (6.13-7.17 years) at varying risk for dyslexia by training artificial letter-speech sound correspondences within a single experimental session. Subsequently, we acquired simultaneously event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) scans during implicit audiovisual presentation of trained and untrained pairs. Audiovisual integration of trained pairs correlated with individual learning rates in right superior temporal, left inferior temporal, and bilateral parietal areas and with phonological awareness in left temporal areas. In correspondence, a differential left-lateralized parietooccipitotemporal ERP at 400 ms for trained pairs correlated with learning achievement and familial risk. Finally, a late (650 ms) posterior negativity indicating audiovisual congruency of trained pairs was associated with increased fMRI activation in the left occipital cortex. Taken together, a short (<30 min) letter-speech sound training initializes audiovisual integration in neural systems that are responsible for processing linguistic information in proficient readers. To conclude, the ability to learn grapheme-phoneme correspondences, the familial history of reading disability, and phonological awareness of prereading children account for the degree of audiovisual integration in a distributed brain network. Such findings on emerging linguistic audiovisual integration could allow for distinguishing between children with typical and atypical reading development. Hum Brain Mapp 38:1038-1055, 2017. © 2016 Wiley Periodicals, Inc.

The level of audiovisual print-speech integration deficits in dyslexia.

The classical phonological deficit account of dyslexia is increasingly linked to impairments in grapho-phonological conversion, and to dysfunctions in superior temporal regions associated with audiovisual integration. The present study investigates mechanisms of audiovisual integration in typical and impaired readers at the critical developmental stage of adolescence. Congruent and incongruent audiovisual as well as unimodal (visual only and auditory only) material was presented. Audiovisual presentations were single letters and three-letter (consonant-vowel-consonant) stimuli accompanied by matching or mismatching speech sounds. Three-letter stimuli exhibited fast phonetic transitions as in real-life language processing and reading. Congruency effects, i.e. different brain responses to congruent and incongruent stimuli were taken as an indicator of audiovisual integration at a phonetic level (grapho-phonological conversion). Comparisons of unimodal and audiovisual stimuli revealed basic, more sensory aspects of audiovisual integration. By means of these two criteria of audiovisual integration, the generalizability of audiovisual deficits in dyslexia was tested. Moreover, it was expected that the more naturalistic three-letter stimuli are superior to single letters in revealing group differences. Electrophysiological and hemodynamic (EEG and fMRI) data were acquired simultaneously in a simple target detection task. Applying the same statistical models to event-related EEG potentials and fMRI responses allowed comparing the effects detected by the two techniques at a descriptive level. Group differences in congruency effects (congruent against incongruent) were observed in regions involved in grapho-phonological processing, including the left inferior frontal and angular gyri and the inferotemporal cortex. Importantly, such differences also emerged in superior temporal key regions. Three-letter stimuli revealed stronger group differences than single letters. No significant differences in basic measures of audiovisual integration emerged. Convergence of hemodynamic and electrophysiological signals appeared to be limited and mainly occurred for highly significant and large effects in visual cortices. The findings suggest efficient superior temporal tuning to audiovisual congruency in controls. In impaired readers, however, grapho-phonological conversion is effortful and inefficient, although basic audiovisual mechanisms seem intact. This unprecedented demonstration of audiovisual deficits in adolescent dyslexics provides critical evidence that the phonological deficit might be explained by impaired audiovisual integration at a phonetic level, especially for naturalistic and word-like stimulation.

Development of the automatic mismatch response: from frontal positivity in kindergarten children to the mismatch negativity.

OBJECTIVE: The automatic event-related potential (ERP) response to auditory deviance typically consists of a frontocentral mismatch negativity (MMN), which has been shown to be quite stable during development. Whereas in some infant studies, positive frontal mismatch responses have been reported instead of a MMN; to date, such positivities have not been reported for older children. METHODS: Oddball sequences with small frequency and phoneme deviance (standard: 1000 Hz, 'ba'; larger deviance: 1060 Hz, 'ta'; smaller deviance: 1030 Hz, 'da') and short intervals (every 0.38 s) were presented to 6-7-year-old children and adults during 43-channel ERP recordings. RESULTS: Children showed a consistent frontal positive mismatch response with posterior negativity (179-207 ms), and adults a frontocentral MMN with mastoid positivity (129-199 ms). This map polarity reversal was reflected by significantly different 3D centroid distributions. Low-resolution electromagnetic tomography (LORETA) revealed temporal mismatch response sources for both age groups and conditions. CONCLUSIONS: Major developmental changes characterise the automatic mismatch response for the small deviances and short intervals used. Source localisation suggests that children's and adults' mismatch responses originated from superior temporal plane generators with similar localisation but opposite polarity. This indicates qualitatively different neurophysiological functioning of the automatic bi-temporal auditory change detectors in children and adults.