The emergence of dyslexia in the developing brain.

Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Based on standardised and age-normed reading and spelling tests administered at school age, children were classified as 16 dyslexic participants and 16 controls. This longitudinal design allowed us to disentangle possible neurobiological predispositions for developing dyslexia from effects of individual differences in literacy experience. In our sample, the disorder can be predicted already before literacy learning from auditory cortex gyrification and aberrant downstream connectivity within the speech processing system. These results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction.

Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements.

Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future.

Atypical resting synchrony in autism spectrum disorder.

Autism spectrum disorder (ASD) is increasingly understood to be associated with aberrant functional brain connectivity. Few studies, however, have described such atypical neural synchrony among specific brain regions. Here, we used magnetoencephalography (MEG) to characterize alterations in functional connectivity in adolescents with ASD through source space analysis of phase synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and 15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided reconstruction of neural activity at various cortical and subcortical regions was performed and inter-regional phase synchrony was calculated in physiologically relevant frequency bands. Using a multilevel approach, we characterized atypical resting-state synchrony within specific anatomically defined networks as well as altered network topologies at both regional and whole-network scales. Adolescents with ASD demonstrated frequency-dependent alterations in inter-regional functional connectivity. Hyperconnectivity was observed among the frontal, temporal, and subcortical regions in beta and gamma frequency ranges. In contrast, parietal and occipital regions were hypoconnected to widespread brain regions in theta and alpha bands in ASD. Furthermore, we isolated a hyperconnected network in the gamma band in adolescents with ASD which encompassed orbitofrontal, subcortical, and temporal regions implicated in social cognition. Results from graph analyses confirmed that frequency-dependent alterations of network topologies exist at both global and local levels. We present the first source-space investigation of oscillatory phase synchrony in resting-state MEG in ASD. This work provides evidence of atypical connectivity at physiologically relevant time scales and indicates that alterations of functional connectivity in adolescents with ASD are frequency dependent and region dependent.

Voice categorization in the four-month-old human brain.

Voices are the most relevant social sounds for humans and therefore have crucial adaptive value in development. Neuroimaging studies in adults have demonstrated the existence of regions in the superior temporal sulcus that respond preferentially to voices. Yet, whether voices represent a functionally specific category in the young infant's mind is largely unknown. We developed a highly sensitive paradigm relying on fast periodic auditory stimulation (FPAS) combined with scalp electroencephalography (EEG) to demonstrate that the infant brain implements a reliable preferential response to voices early in life. Twenty-three 4-month-old infants listened to sequences containing non-vocal sounds from different categories presented at 3.33 Hz, with highly heterogeneous vocal sounds appearing every third stimulus (1.11 Hz). We were able to isolate a voice-selective response over temporal regions, and individual voice-selective responses were found in most infants within only a few minutes of stimulation. This selective response was significantly reduced for the same frequency-scrambled sounds, indicating that voice selectivity is not simply driven by the envelope and the spectral content of the sounds. Such a robust selective response to voices as early as 4 months of age suggests that the infant brain is endowed with the ability to rapidly develop a functional selectivity to this socially relevant category of sounds.

Resting Frontal Gamma Power is Associated with Both Expressive Language and Non-verbal Cognitive Abilities in Young Autistic Children.

Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosed with autism spectrum disorder (ASD). The current study evaluates differences in resting frontal gamma power between young autistic and NT children and tests whether gamma power is uniquely associated with individual differences in expressive language, receptive language and non-verbal cognitive abilities in autistic and NT children. Participants included 48 autistic children and 58 age- and sex-matched NT children (ages 22-60 months). Baseline electroencephalography (EEG) recordings were acquired from each participant. Children also completed the Mullen Scales of Early Learning (MSEL). We found that frontal gamma power at rest did not differ between autistic and NT children. Among autistic children, reduced frontal gamma power was significantly associated with both higher expressive language skills and higher non-verbal cognitive skills, controlling for age and sex. The interaction between frontal gamma power and diagnostic status no longer explained unique variance in expressive language skills after controlling for variance associated with non-verbal cognitive skills across autistic and NT children. Together, these findings suggest that reduced gamma power is associated with both better expressive language and non-verbal cognitive skills among young autistic children. Moreover, associations between high frequency neural activity and cognition are not specific to verbal abilities but reflect neural mechanisms associated with general higher-order cognitive abilities in ASD.

Sensitivity and specificity in affective and social learning in adolescence.

Adolescence is a period of heightened affective and social sensitivity. In this review we address how this increased sensitivity influences associative learning. Based on recent evidence from human and rodent studies, as well as advances in computational biology, we suggest that, compared to other age groups, adolescents show features of heightened Pavlovian learning but tend to perform worse than adults at instrumental learning. Because Pavlovian learning does not involve decision-making, whereas instrumental learning does, we propose that these developmental differences might be due to heightened sensitivity to rewards and threats in adolescence, coupled with a lower specificity of responding. We discuss the implications of these findings for adolescent mental health and education.

Neuroscience in Education: A Bridge Too Far or One That Has Yet to Be Built: Introduction to the "Brain Goes to School".

There have been numerous detractors and supporters relating to attempts to merge the neurosciences and the knowledge base of related contributing disciplines with the field of education. Some have argued that this is a "bridge too far". The predominant view is that the relationship between neuroscience and the classroom has been neither significantly examined, nor applied. What is needed is a specially trained class of professionals whose role it would be to guide the introduction of cognitive neuroscience into educational practice in a sensible and ethical manner. Neuroeducators would play a pivotal role in assessing the quality of evidence purporting to be relevant to education, assessing who is best placed to employ newly developed knowledge, as well as with what safeguards, in addition to investigating how to deal with unexpected consequences of implemented research findings. This special issue of the "The Brain Goes to School" aims to provide support for the development of training programs that truly integrate curriculum design and classroom instruction with the developmental cognitive neurosciences.

The Neural Basis of Social Cognition in Typically Developing Children and Its Relationship to Social Functioning.

Theory of mind (ToM), the ability to think about the perspectives, beliefs, and feelings of another, develops throughout childhood and adolescence and is an important skill for social interactions. This study examines neural activity in typically developing children during a novel ToM task - the Movie Mentalizing Task- and tests its relations to ToM behavioral performance and social functioning. In this fMRI task, children ages 8-13years (N=25) watched a brief movie clip and were asked to predict a character's mental state after a social interaction. Engaging in the Movie Mentalizing Task activated the ToM neural network. Moreover, greater neural activity in the ToM network, including the superior temporal gyrus and inferior frontal gyrus, was associated with better behavioral performance on independent ToM tasks and was related to better social functioning, though these results do not survive correction for multiple comparisons. Results offer a new affective theory of mind task for children in the scanner that robustly recruits activity in theory of mind regions.

Activation for newly learned words in left medial-temporal lobe during toddlers' sleep is associated with memory for words.

Little is known about the neural substrates underlying early memory functioning. To gain more insight, we examined how toddlers remember newly learned words. Hippocampal and anterior medial-temporal lobe (MTL) processes have been hypothesized to support forming and retaining the association between novel words and their referents, but direct evidence of this connection in early childhood is lacking. We assessed 2-year-olds (n = 38) for their memory of newly learned pseudowords associated with novel objects and puppets. We tested memory for these associations during the same session as learning and after a 1-week delay. We then played these pseudowords, previously known words, and completely novel pseudowords during natural nocturnal sleep, while collecting functional magnetic resonance imaging data. Activation in the left hippocampus and the left anterior MTL for newly learned compared to novel words was associated with same-session memory for these newly learned words only when they were learned as puppet names. Activation for known words was associated with memory for puppet names at the 1-week delay. Activation for newly learned words was also associated with overall productive vocabulary. These results underscore an early developing link between memory mechanisms and word learning in the medial temporal lobe.

Dysregulation of temporal dynamics of synchronous neural activity in adolescents on autism spectrum.

Autism spectrum disorder is increasingly understood to be based on atypical signal transfer among multiple interconnected networks in the brain. Relative temporal patterns of neural activity have been shown to underlie both the altered neurophysiology and the altered behaviors in a variety of neurogenic disorders. We assessed brain network dynamics variability in autism spectrum disorders (ASD) using measures of synchronization (phase-locking) strength, and timing of synchronization and desynchronization of neural activity (desynchronization ratio) across frequency bands of resting-state electroencephalography (EEG). Our analysis indicated that frontoparietal synchronization is higher in ASD but with more short periods of desynchronization. It also indicates that the relationship between the properties of neural synchronization and behavior is different in ASD and typically developing populations. Recent theoretical studies suggest that neural networks with a high desynchronization ratio have increased sensitivity to inputs. Our results point to the potential significance of this phenomenon to the autistic brain. This sensitivity may disrupt the production of an appropriate neural and behavioral responses to external stimuli. Cognitive processes dependent on the integration of activity from multiple networks maybe, as a result, particularly vulnerable to disruption. Autism Res 2020, 13: 24-31. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Parts of the brain can work together by synchronizing the activity of the neurons. We recorded the electrical activity of the brain in adolescents with autism spectrum disorder and then compared the recording to that of their peers without the diagnosis. We found that in participants with autism, there were a lot of very short time periods of non-synchronized activity between frontal and parietal parts of the brain. Mathematical models show that the brain system with this kind of activity is very sensitive to external events.

On the genesis of spatial-numerical associations: Evolutionary and cultural factors co-construct the mental number line.

Mapping numbers onto space is a common cognitive representation that has been explored in both behavioral and neuroimaging contexts. Empirical work probing the diverse nature of these spatial-numerical associations (SNAs) has led researchers to question 1) how the human brain links numbers with space, and 2) whether this link is biologically vs. culturally determined. We review the existing literature on the development of SNAs and situate that empirical work within cognitive and neuroscientific theoretical frameworks. We propose that an evolutionarily-ancient frontal-parietal circuit broadly tuned to multiple magnitude dimensions provides the phylogenetic substrate for SNAs, while enculturation and sensorimotor experience shape their specific profiles. We then use this perspective to discuss educational implications and highlight promising avenues for future research.

The Fallacy of Univariate Solutions to Complex Systems Problems.

Complex biological systems, by definition, are composed of multiple components that interact non-linearly. The human brain constitutes, arguably, the most complex biological system known. Yet most investigation of the brain and its function is carried out using assumptions appropriate for simple systems-univariate design and linear statistical approaches. This heuristic must change before we can hope to discover and test interventions to improve the lives of individuals with complex disorders of brain development and function. Indeed, a movement away from simplistic models of biological systems will benefit essentially all domains of biology and medicine. The present brief essay lays the foundation for this argument.

Evidence for an inhibitory-control theory of the reasoning brain.

In this article, we first describe our general inhibitory-control theory and, then, we describe how we have tested its specific hypotheses on reasoning with brain imaging techniques in adults and children. The innovative part of this perspective lies in its attempt to come up with a brain-based synthesis of Jean Piaget's theory on logical algorithms and Daniel Kahneman's theory on intuitive heuristics.

Children's belief- and desire-reasoning in the temporoparietal junction: evidence for specialization from functional near-infrared spectroscopy.

Behaviorally, children's explicit theory of mind (ToM) proceeds in a progression of mental-state understandings: developmentally, children demonstrate accurate explicit desire-reasoning before accurate explicit belief-reasoning. Given its robust and cross-cultural nature, we hypothesize this progression may be paced in part by maturation/specialization of the brain. Neuroimaging research demonstrates that the right temporoparietal junction (TPJ) becomes increasingly selective for ToM reasoning as children age, and as their ToM improves. But this research has narrowly focused on beliefs or on undifferentiated mental-states. A recent ERP study in children included a critical contrast to desire-reasoning, and demonstrated that right posterior potentials differentiated belief-reasoning from desire-reasoning. Taken together, the literature suggests that children's desire-belief progression may be paced by specialization of the right TPJ for belief-reasoning specifically, beyond desire-reasoning. In the present study, we tested this hypothesis directly by examining children's belief- and desire-reasoning using functional near-infrared spectroscopy in conjunction with structural magnetic resonance imaging to pinpoint brain activation in the right TPJ. Results showed greatest activation in the right TPJ for belief-reasoning, beyond desire-reasoning, and beyond non-mental reasoning (control). Findings replicate and critically extend prior ERP results, and provide clear evidence for a specific neural mechanism underlying children's progression from understanding desires to understanding beliefs.

Network-Level Connectivity Dynamics of Movie Watching in 6-Year-Old Children.

Better understanding of the developing brain's functional mechanisms is critical for improving diagnosis and treatment of different developmental disorders. Particularly, characterizing how the developing brain dynamically reorganizes during different cognitive states may offer novel insight into the neuronal mechanisms of cognitive deficits. Imaging the brain during naturalistic conditions, like movie watching, provides a highly practical way to study young children's developing functional brain systems. In this study we compared the network-level functional organization of 6-year-old children while they were at rest with their functional connectivity as they watched short video clips. We employed both a data-driven independent component analysis (ICA) approach and a hypothesis-driven seed-based analysis to identify changes in network-level functional interactions during the shift from resting to video watching. Our ICA results showed that naturally watching a movie elicits significant changes in the functional connectivity between the visual system and the dorsal attention network when compared to rest (t (32) = 5.02, p = 0.0001). More interestingly, children showed an immature, but qualitatively adult-like, pattern of reorganization among three of the brain's higher-order networks (frontal control, default-mode and dorsal attention). For both ICA and seed-based approaches, we observed a decrease in the frontal network's correlation with the dorsal attention network (ICA: t (32) = -2.46, p = 0.02; Seed-based: t (32) = -1.62, p =0.12) and an increase in its connectivity with the default mode network (ICA: t (32) = 2.84, p = 0.008; Seed-based: t (32) = 2.28, p =0.03), which is highly consistent with the pattern observed in adults. These results offer improved understanding of the developing brain's dynamic network-level interaction patterns during the transition between different brain states and call for further studies to examine potential alterations to such dynamic patterns in different developmental disorders.

Neuromagnetic vistas into typical and atypical development of frontal lobe functions.

The frontal lobes are involved in many higher-order cognitive functions such as social cognition executive functions and language and speech. These functions are complex and follow a prolonged developmental course from childhood through to early adulthood. Magnetoencephalography (MEG) is ideal for the study of development of these functions, due to its combination of temporal and spatial resolution which allows the determination of age-related changes in both neural timing and location. There are several challenges for MEG developmental studies: to design tasks appropriate to capture the neurodevelopmental trajectory of these cognitive functions, and to develop appropriate analysis strategies to capture various aspects of neuromagnetic frontal lobe activity. Here, we review our MEG research on social and executive functions, and speech in typically developing children and in two clinical groups - children with autism spectrum disorder and children born very preterm. The studies include facial emotional processing, inhibition, visual short-term memory, speech production, and resting-state networks. We present data from event-related analyses as well as on oscillations and connectivity analyses and review their contributions to understanding frontal lobe cognitive development. We also discuss the challenges of testing young children in the MEG and the development of age-appropriate technologies and paradigms.

Intellectual development in autism spectrum disorders: new insights from longitudinal studies.

The presence/absence of Intellectual Disability (ID) is considered to be the most critical factor affecting outcomes in individuals with Autism Spectrum Disorders (ASD). However, the question of the specific nature of ID in ASD has received little attention, with the current view being that ID is a comorbid condition (i.e., one that is unrelated in etiology and causality from the ASD itself). Recent advances in developmental neuroscience, highlighting the importance of early exposure to social experiences for cognitive development, support an alternative view; that ID in ASD might emerge as a consequence of severe social-communication deficits on the experience-dependent mechanisms underlying neurocognitive development. We tested this prediction in two independent samples of young children with ASD (Ns = 23 and 60), finding that children with greater ASD severity at an initial assessment were more likely to present with poorer cognitive outcomes at a later assessment, irrespective of initial cognitive level. The results of this proof of principle study suggest that ASD symptom severity contributes to the extent to which the environmental input required to support "typical" brain development can be processed by the individual, so that the risk of developing ID increases as the number and severity of ASD social-communicative impairments increase.