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Background Understanding the mechanisms in the brain’s incentive network that give rise to symptoms of major depressive disorder (MDD) during adolescence provides new perspectives to address MDD in early stages of development. This functional magnetic resonance imaging study determines whether instrumental vigor and brain responses to appetitive and aversive monetary incentives are altered in adolescent MDD and associated with symptom severity. Methods Adolescents with moderate to severe MDD (n = 30, mean age [SD] = 16.1 [1.4] years) and healthy control subjects (n = 33, mean age = 16.2 [1.9] years) matched for age, sex, and IQ performed a monetary incentive delay task. During outcome presentation, prediction error signals were used to study the response and coupling of the incentive network during learning of cue-outcome associations. A computational reinforcement model was used to assess adaptation of response vigor. Brain responses and effective connectivity to model-derived prediction errors were assessed and related to depression severity and anhedonia levels. Results Participants with MDD behaved according to a more simplistic learning model and exhibited slower learning. Effective connectivity analysis of functional magnetic resonance imaging data revealed that impaired loss error processing in the orbitofrontal cortex was associated with aberrant gain control. Anhedonia scores correlated with loss-related error signals in the posterior insula and habenula. Conclusions Adolescent MDD is selectively related to impaired processing of error signals during loss, but not reward, in the orbitofrontal cortex. Aberrant evaluation of loss outcomes might reflect an early mechanism of how negative bias and helplessness manifest in the brain. This approach sheds light on pathomechanisms in MDD and may improve early diagnosis and treatment selection., Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7 (3), ISSN:2451-9022, ISSN:2451-9030

Humans have an extraordinary ability to interact and cooperate with others. Despite the social and evolutionary significance of collaboration, research on finding its neural correlates has been limited partly due to restrictions on the simultaneous neuroimaging of more than one participant (also known as hyperscanning). Several studies have used dyadic fMRI hyperscanning to examine the interaction between two participants. However, to our knowledge, no study to date has aimed at revealing the neural correlates of social interactions using a three-person (or triadic) fMRI hyperscanning paradigm. Here, we simultaneously measured the blood-oxygenation level-dependent signal from 12 triads (n = 36 participants), while they engaged in a collaborative drawing task based on the social game of Pictionary. General linear model analysis revealed increased activation in the brain regions previously linked with the theory of mind during the collaborative phase compared to the independent phase of the task. Furthermore, using intersubject correlation analysis, we revealed increased synchronization of the right temporo‐parietal junction (R TPJ) during the collaborative phase. The increased synchrony in the R TPJ was observed to be positively associated with the overall team performance on the task. In sum, our paradigm revealed a vital role of the R TPJ among other theory-of-mind regions during a triadic collaborative drawing task.

Published Nov 17, 2021 The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connections in vivo, in part based on the reliability of analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability, and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to establish the reliability of computational analysis pipelines in neuroimaging. This work was supported through grant 1RF1MH121868- 01 from the National Institute of Mental Health/the BRAIN Initiative, through grant 5R01EB027585-02 to Eleftherios Garyfallidis (Indiana University) from the National Institute of Biomedical Imaging and Bioengineering, through Azure Cloud Computing Credits for Research & Teaching provided through the University of Washington’s Research Computing unit and the University of Washington eScience Institute, and NICHD R21HD092771 to Jason D. Yeatman

Number processing abilities are important for academic and personal development. The course of initial specialization of ventral occipito-temporal cortex (vOTC) for visual number processing is crucial for the development of numeric and arithmetic skills. We examined the visual N1, the electrophysiological correlate of vOTC activations across five time points in kindergarten (T1), middle and end of first grade (T2, T3), second (T4) and fifth grade (T5). 62 children (35 female) performed a target detection task which included visual presentation of digits, false fonts, and letters. Arithmetic skills were measured at T4 and T5 with standardized math tests. Stronger N1 amplitudes for digits than false fonts were found across all 5 measurements. Arithmetic skills correlated negatively with visual N1 sensitivity to digits at T4 (2nd grade, mean age 8.3 yrs) over the left hemisphere, possibly reflecting allocation of more attentional or cognitive resources with poorer arithmetic skills. Our main result shows persistent visual N1 sensitivity to digits that is already present early on in pre-school and remains stable until fifth grade. This differs from the relatively sharp rise and fall of the visual N1 sensitivity to words or letters between kindergarten and middle of elementary school. The present study thus indicates different trajectories in the development of visual processing for written characters that are relevant to numeracy and literacy.

Letters, foundational units of alphabetic writing systems, are quintessential to human culture. The ability to read, indispensable to perform in today's society, necessitates a reorganization of visual cortex for fast letter recognition, but the developmental course of this process has not yet been characterized. Here, we show the emergence of visual sensitivity to letters across five electroencephalography measurements from kindergarten and throughout elementary school and relate this development to emerging reading skills. We examined the visual N1, the electrophysiological correlate of ventral occipito-temporal cortex activation in 65 children at varying familial risk for dyslexia. N1 letter sensitivity emerged in first grade, when letter sound knowledge gains were most pronounced and decayed shortly after when letter knowledge is consolidated, showing an inverted U-shaped development. This trajectory can be interpreted within an interactive framework that underscores the influence of top-down predictions. While the N1 amplitudes to letters correlated with letter sound knowledge at the beginning of learning, no association between the early N1 letter response and later reading skills was found. In summary, the current findings provide an important reference point for our neuroscientific understanding of learning trajectories and the process of visual specialization during skill learning., Developmental Cognitive Neuroscience, 49, ISSN:1878-9293, ISSN:1878-9307

Over the past two decades, researchers have tried to uncover how the human brain can extract linguistic information from a sequence of visual symbols. The description of how the brain’s visual system processes words and enables reading has improved with the progressive refinement of experimental methodologies and neuroimaging techniques. This review provides a brief overview of this research journey. We start by describing classical models of object recognition in non-human primates, which represent the foundation for many of the early models of visual word recognition in humans. We then review functional neuroimaging studies investigating the word-selective regions in visual cortex. This research led to the differentiation of highly specialized areas, which are involved in the analysis of different aspects of written language. We then consider the corresponding anatomical measurements and provide a description of the main white matter pathways carrying neural signals crucial to word recognition. Finally, in an attempt to integrate structural, functional, and electrophysiological findings, we propose a view of visual word recognition, accounting for spatial and temporal facets of word-selective neural processes. This multi-modal perspective on the neural circuitry of literacy highlights the relevance of a posterior-anterior differentiation in ventral occipitotemporal cortex for visual processing of written language and lexical features. It also highlights unanswered questions that can guide us towards future research directions. Bridging measures of brain structure and function will help us reach a more precise understanding of the transformation from vision to language.

Published18 March 2021 An accurate model of the factors that contribute to individual differences in reading ability depends on data collection in large, diverse and representative samples of research participants. However, that is rarely feasible due to the constraints imposed by standardized measures of reading ability which require test administration by trained clinicians or researchers. Here we explore whether a simple, two-alternative forced choice, time limited lexical decision task (LDT), self-delivered through the webbrowser, can serve as an accurate and reliable measure of reading ability. We found that performance on the LDT is highly correlated with scores on standardized measures of reading ability such as the Woodcock-Johnson Letter Word Identification test (r = 0.91, disattenuated r = 0.94). Importantly, the LDT reading ability measure is highly reliable (r = 0.97). After optimizing the list of words and pseudowords based on item response theory, we found that a short experiment with 76 trials (2–3 min) provides a reliable (r = 0.95) measure of reading ability. Thus, the self-administered, Rapid Online Assessment of Reading ability (ROAR) developed here overcomes the constraints of resourceintensive, in-person reading assessment, and provides an efficient and automated tool for effective online research into the mechanisms of reading (dis)ability. We would like to thank the Pavlovia and PsychoPy team for their support on the browser-based experiments. This work was funded by NIH NICHD R01HD09586101, research grants from Microsoft and Jacobs Foundation Research Fellowship to J.D.Y.

Sex chromosome aneuploidies (SCA) are associated with an increased risk for specific learning disorders (SLD). Individuals with Klinefelter Syndrome (KS) show an increased incidence of developmental dyslexia and individuals with Turner Syndrome (TS) are often affected by developmental dyscalculia. Accordingly, KS frequently coincides with verbal deficits, and TS with visual-spatial impairments. Though neurocognitive profiles of KS and TS are well-established, little is known about the neurobiology underling learning in SCA. This review summarizes current structural and functional magnetic resonance imaging (MRI) studies in KS and TS related to literacy and mathematical skills. It includes studies that focus on correlates between brain anatomy and cognition in SCA and on functional brain responses during learning-related tasks and at rest. We highlight important neural circuits that are related to domain-specific skills of literacy and mathematics. We discuss how identifying neuroendophenotypes of learning in SCA might contribute to developing a novel framework for SLD that accounts for potential genetic effects on learning, and from the X and Y chromosomes specifically. Future research directions are considered to establish clear brain-behavior relationships that might ultimately improve the treatment of SLD in SCA across development.

We assessed the Swiss-German version of GraphoLearn, a computer game designed to support reading by training grapheme-phoneme correspondences. A group of 34 children at risk for dyslexia trained three times a week during 14 weeks, on top of their standard school instruction. The sample was divided into two groups of 18 and 16 children, who started training at either the middle or the end of first grade. We found beneficial training effects in pseudoword reading in both training groups and for rapid automatized naming skills in the group that trained earlier. Our results suggest that both the efficiency in phonological decoding and rapid access to verbal representations are susceptible to facilitation by GraphoLearn. These findings confirm the utility of the training software as a tool to support school instruction and reading-related abilities in beginning readers. We discuss ideas to improve the content and outcomes of future versions of the training software.

The ability to enhance motivated performance through incentives is crucial to guide and ultimately optimise the outcome of goal-directed behaviour. It remains largely unclear how motivated behaviour and performance develops particularly across adolescence. Here, we used computational fMRI to assess how response speed and its underlying neural circuitry are modulated by reward and loss in a monetary incentive delay paradigm. We demonstrate that maturational fine-tuning of functional coupling within the cortico-striatal incentive circuitry from adolescence to adulthood facilitates the ability to enhance performance selectively for higher subjective values. Additionally, during feedback, we found developmental sex differences of striatal representations of reward prediction errors in an exploratory analysis. Our findings suggest that a reduced capacity to utilise subjective value for motivated behaviour in adolescence is rooted in immature information processing in the incentive system. This indicates that the neurocircuitry for coordination of incentivised, motivated cognitive control acts as a bottleneck for behavioural adjustments in adolescence., NeuroImage, 237, ISSN:1053-8119, ISSN:1095-9572

Neural tuning to print develops when children learn to read and is reflected by a more pronounced left occipito-temporal negativity to orthographic stimuli as compared to non-orthographic false fonts or symbols after around 150–250 ms in their N1, a visual event-related potential (ERP). In adults, initial expertise for a novel script can emerge in less than 2 hours through repeated exposure or training. Here, we aimed to assess changes in the visual N1 related to the process of learning associations between unknown written characters and familiar, spoken syllables or words. Thirty-two healthy literate adults learned to associate a set of foreign characters with either syllables or German words within a single experimental session. EEG was recorded during a visual one-back character repetition detection task in which trained characters, untrained characters and familiar letters were presented before and after the training. A bilateral occipito-temporal increase in the N1 negativity with training was only found for the newly learned characters, but not for the control characters. In conclusion, the present data indicate that expertise to novel characters can be induced by a short character–sound association training and is reflected by a bilateral modulation of the visual N1 amplitude. However, no differentiation was found regarding the comparison of word or syllable training, indicating that the visual N1 most likely reflects gaining expertise driven by phonological associations common to both training types.

The ventral occipitotemporal (vOT) cortex serves as a core region for visual processing, and specific areas of this region show preferential activation for various visual categories such as faces and print. The emergence of such functional specialization in the human cortex represents a pivotal developmental process, which provides a basis for targeted and efficient information processing. For example, functional specialization to print in the left vOT is an important prerequisite for fluent reading. However, it remains unclear, which processes initiate the preferential cortical activations to characters arising in the vOT during child development. Using a multimodal neuroimaging approach with preschool children at familial risk for developmental dyslexia, we demonstrate how varying levels of expertise modulate the neural response to single characters, which represent the building blocks of print units. The level of expertise to characters was manipulated firstly through brief training of false-font speech–sound associations and secondly by comparing characters for which children differed in their level of familiarity and expertise accumulated through abundant exposure in their everyday environment. Neural correlates of character processing were tracked with simultaneous high-density electroencephalography and functional magnetic resonance imaging in a target detection task. We found training performance and expertise-dependent modulation of the visual event-related potential around 220 ms (N1) and the corresponding vOT activation. Additionally, trained false-font characters revealed stronger functional connectivity between the left fusiform gyrus (FFG) seed and left superior parietal/lateral occipital cortex regions with higher training performance. In sum, our results demonstrate that learning artificial-character speech–sound associations enhances activation to trained characters in the vOT and that the magnitude of this activation and the functional connectivity of the left FFG to the parieto-occipital cortex depends on learning performance. This pattern of results suggests emerging development of the reading network after brief training that parallels network specialization during reading acquisition., NeuroImage, 189, ISSN:1053-8119, ISSN:1095-9572

In a recent opinion article, we explained why we think that defining developmental dyslexia as a neurodevelopmental disorder and neuroimaging studies on dyslexia are useful. A recent response has made some claims of generalized misinterpretation and misconception in the field. Since that was a direct reply to our article, we would like to clarify our opinion on some of those claims., Brain Sciences, 9 (3)

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 (

* Abbreviation: SLD — : specific learning disorder It is not uncommon for children with specific learning disorders (SLDs) to go through several years of school without receiving necessary academic support, emphasizing the need for earlier detection. Precursor skills of learning often provide important, early indications about whether a child might be at risk for developing an SLD. In this issue of Pediatrics, Sanfilippo et al1 provide a timely overview of current evidence on precursors of reading and outline how pediatricians can contribute to early identification of children at risk for dyslexia. Sanfilippo et al1 highlight “red flags” that can assist pediatricians in identifying dyslexia, including screening for family history, language development, and early literacy skills. Screening may be composed of cognitive-behavioral assessments that typically focus on phonological awareness, basic letter knowledge, vocabulary size, and language comprehension. Given that SLDs are of neurobiological origin, neuroimaging techniques have been used to investigate neural signatures of these precursor skills.2 Increasing evidence suggests that neurobiological markers can predict individual reading outcomes, outperforming the prediction accuracy of cognitive-behavioral precursors of literacy.3,4 As the authors point out, neuroimaging screenings are not (yet) available, … Address correspondence to Iliana I. Karipidis, PhD, Department of Psychiatry and Behavioral Sciences, Stanford Medicine, Stanford University, 401 Quarry Rd, Stanford, CA 94305, E-mail: ilianak{at}stanford.edu

Women are known to have stronger prosocial preferences than men, but it remains an open question as to how these behavioural differences arise from differences in brain functioning. Here, we provide a neurobiological account for the hypothesized gender difference. In a pharmacological study and an independent neuroimaging study, we tested the hypothesis that the neural reward system encodes the value of sharing money with others more strongly in women than in men. In the pharmacological study, we reduced receptor type-specific actions of dopamine, a neurotransmitter related to reward processing, which resulted in more selfish decisions in women and more prosocial decisions in men. Converging findings from an independent neuroimaging study revealed gender-related activity in neural reward circuits during prosocial decisions. Thus, the neural reward system appears to be more sensitive to prosocial rewards in women than in men, providing a neurobiological account for why women often behave more prosocially than men. A large body of evidence suggests that women are often more prosocial (for example, generous, altruistic and inequality averse) than men, at least when other factors such as reputation and strategic considerations are excluded1,2,3. This dissociation could result from cultural expectations and gender stereotypes, because in Western societies women are more strongly expected to be prosocial4,5,6 and sensitive to variations in social context than men1. It remains an open question, however, whether and how on a neurobiological level the social preferences of women and men arise from differences in brain functioning. The assumption of gender differences in social preferences predicts that the neural reward system’s sensitivity to prosocial and selfish rewards should differ between women and men. Specifically, the hypothesis would be that the neural reward system is more sensitive to prosocial than selfish rewards in women and more sensitive to selfish than prosocial rewards in men. The goal of the current study was to test in two independent experiments for the hypothesized gender differences on both a pharmacological and a haemodynamic level. In particular, we examined the functions of the neurotransmitter dopamine using a dopamine receptor antagonist, and the role of the striatum (a brain region strongly innervated by dopamine neurons) during social decision-making in women and men using neuroimaging. The neurotransmitter dopamine is thought to play a key role in neural reward processing7,8. Recent evidence suggests that dopaminergic activity is sensitive not only to rewards for oneself but to rewards for others as well9. The assumption that dopamine is sensitive to both self- and other-related outcomes is consistent with the finding that the striatum shows activation for both selfish and shared rewards10,11,12,13,14,15. The dopaminergic response may represent a net signal encoding the difference between the value of preferred and unpreferred rewards8. Regarding the hypothesized gender differences in social preferences, this account makes the following predictions. If women prefer shared (prosocial) outcomes2, women’s dopaminergic signals to shared rewards will be stronger than to non-shared (selfish) rewards, so reducing dopaminergic activity should bias women to make more selfish decisions. In line with this hypothesis, a functional imaging study reported enhanced striatal activation in female participants during charitable donations11. In contrast, if men prefer selfish over prosocial rewards, dopaminergic activity should be enhanced to selfish compared to prosocial rewards. In line with this view, upregulating dopaminergic activity in a sample of exclusively male participants increased selfish behaviour in a bargaining game16. Thus, contrary to the hypothesized effect in women, reducing dopaminergic neurotransmission should render men more prosocial. Taken together, the current study tested the following three predictions: we expected the dopaminergic reward system (1) to be more sensitive to prosocial than selfish rewards in women and (2) to be more sensitive to selfish than prosocial rewards in men. As a consequence of these two predictions, we also predicted (3) dopaminoceptive regions such as the striatum to show stronger activation to prosocial relative to selfish rewards in women than in men. To test these predictions, we conducted a pharmacological study in which we reduced dopaminergic neurotransmission with amisulpride. Amisulpride is a dopamine antagonist that is highly specific for dopaminergic D2/D3 receptors17. After receiving amisulpride or placebo, participants performed an interpersonal decision task18,19,20, in which they made choices between a monetary reward only for themselves (selfish reward option) and sharing money with others (prosocial reward option). We expected that blocking dopaminergic neurotransmission with amisulpride, relative to placebo, would result in fewer prosocial choices in women and more prosocial choices in men. To investigate whether potential gender-related effects of dopamine are selective for social decision-making, we also tested the effects of amisulpride on time preferences in a non-social control task that was matched to the interpersonal decision task in terms of choice structure. In addition, because dopaminergic neurotransmission plays a crucial role in brain regions involved in value processing, such as the striatum21, a gender-related role of dopaminergic activity for social decision-making should also be reflected by dissociable activity patterns in the striatum. Therefore, to further test our hypothesis, we investigated the neural correlates of social decision-making in a functional imaging study. In line with our predictions for the pharmacological study, we expected to find stronger striatum activity during prosocial relative to selfish decisions in women, whereas men should show enhanced activity in the striatum for selfish relative to prosocial choices.

Despite the importance of the prefrontal-amygdala (AMY) network for emotion processing, valence-dependent coupling within this network remains elusive. In this study, we assessed the effect of emotional valence on brain activity and effective connectivity. We tested which functional pathways within the prefrontal-AMY network are specifically engaged during the processing of emotional valence. Thirty-three healthy adults were examined with functional magnetic resonance imaging while performing a dynamic faces and dynamic shapes matching task. The valence of the facial expressions varied systematically between positive, negative, and neutral across the task. Functional contrasts determined core areas of the emotion processing circuitry, comprising the medial prefrontal cortex (MPFC), the right lateral prefrontal cortex (LPFC), the AMY, and the right fusiform face area (FFA). Dynamic causal modelling demonstrated that the bidirectional coupling within the prefrontal-AMY circuitry is modulated by emotional valence. Additionally, Bayesian model averaging showed significant bottom-up connectivity from the AMY to the MPFC during negative and neutral, but not positive, valence. Thus, our study provides strong evidence for alterations of bottom-up coupling within the prefrontal-AMY network as a function of emotional valence. Thereby our results not only advance the understanding of the human prefrontal-AMY circuitry in varying valence context, but, moreover, provide a model to examine mechanisms of valence-sensitive emotional dysregulation in neuropsychiatric disorders., eNeuro, 6 (4), ISSN:2373-2822

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 (

Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance-dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance-dependent other-regarding preferences into an otherwise exclusively own-reward value representation.