Inferring the heritability of large-scale functional networks with a multivariate ACE modeling approach.

Recent evidence suggests that the human functional connectome is stable at different timescales and is unique. These characteristics posit the functional connectome not only as an individual marker but also as a powerful discriminatory measure characterized by high intersubject variability. Among distinct sources of intersubject variability, the long-term sources include functional patterns that emerge from genetic factors. Here, we sought to investigate the contribution of additive genetic factors to the variability of functional networks by determining the heritability of the connectivity strength in a multivariate fashion. First, we reproduced and extended the connectome fingerprinting analysis to the identification of twin pairs. Then, we estimated the heritability of functional networks by a multivariate ACE modeling approach with bootstrapping. Twin pairs were identified above chance level using connectome fingerprinting, with monozygotic twin identification accuracy equal to 57.2% on average for whole-brain connectome. Additionally, we found that a visual (0.37), the medial frontal (0.31), and the motor (0.30) functional networks were the most influenced by additive genetic factors. Our findings suggest that genetic factors not only partially determine intersubject variability of the functional connectome, such that twins can be identified using connectome fingerprinting, but also differentially influence connectivity strength in large-scale functional networks.

Motor Cortex Activation During Writing in Focal Upper-Limb Dystonia: An fNIRS Study.

BACKGROUND: Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. METHODS: We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. RESULTS: Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. CONCLUSIONS: Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.

Individual versus task differences in slow potential generators.

Average slow potentials (SPs) can be computed from any voluntary task, minimally involving attention to anticipated stimuli. Their topography when recorded by large electrode arrays even during simple tasks is complex, multifocal, and its generators appear to be equally multifocal and highly variable across subjects. Various sources of noise of course contaminate such averages and must contribute to the topographic complexity. Here, we report a study in which the non-averaged SP band (0 to 1 Hz) was analyzed by independent components (ICA), from 256 channel recordings of 18 subjects, during four task conditions (resting, visual attention, CPT, and Stroop). We intended to verify whether the replicable SP generators (between two separate day sessions) modeled as current density reconstruction on structural MRI sets were individual-specific, and if putative task-related differences were systematic across subjects. Typically, 3 ICA components (out of 10) explained SPs in each task and subject, and their combined generators were highly variable across subjects: although some occipito-temporal and medial temporal areas contained generators in most subjects; the overall patterns were obviously variable, with no single area common to all 18 subjects. Linear regression modeling to compare combined generators (from all ICA components) between tasks and sessions showed significantly higher correlations between the four tasks than between sessions for each task. Moreover, it was clear that no common task-specific areas could be seen across subjects. Those results represent one more instance in which individual case analyses favor the hypothesis of individual-specific patterns of cortical activity, regardless of task conditions. We discuss this hypothesis with respect to results from the beta band, from individual-case fMRI studies, and its corroboration by functional neurosurgery and the neuropsychology of focal lesions.

Transitions between human functional brain networks reveal complex, cost-efficient and behaviorally-relevant temporal paths.

Resting-state functional MRI activity is organized as a complex network. However, this coordinated brain activity changes with time, raising questions about its evolving temporal arrangement. Does the brain visit different configurations through time in a random or ordered way? Advances in this area depend on developing novel paradigms that would allow us to shed light on these issues. We here propose to study the temporal changes in the functional connectome by looking at transition graphs of network activity. Nodes of these graphs correspond to brief whole-brain connectivity patterns (or meta-states), and directed links to the temporal transition between consecutive meta-states. We applied this method to two datasets of healthy subjects (160 subjects and a replication sample of 54), and found that transition networks had several non-trivial properties, such as a heavy-tailed degree distribution, high clustering, and a modular organization. This organization was implemented at a low biological cost with a high cost-efficiency of the dynamics. Furthermore, characteristics of the subjects' transition graphs, including global efficiency, local efficiency and their transition cost, were correlated with cognition and motor functioning. All these results were replicated in both datasets. We conclude that time-varying functional connectivity patterns of the brain in health progress in time in a highly organized and complex order, which is related to behavior.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths.

BACKGROUND: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. METHODS: We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n = 48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. RESULTS: We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. CONCLUSIONS: We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual's development of psychopathology.

Caudate volume differences among treatment responders, non-responders and controls in children with obsessive-compulsive disorder.

Treatment response in obsessive-compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7-17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).

Reaction time variability and attention-deficit/hyperactivity disorder: is increased reaction time variability specific to attention-deficit/hyperactivity disorder? Testing predictions from the default-mode interference hypothesis.

Increased reaction time variability (RTV) is one of the most replicable behavioral correlates of attention-deficit/hyperactivity disorder (ADHD). However, this may not be specific to ADHD but a more general marker of psychopathology. Here we compare RT variability in individuals with ADHD and those with other childhood internalizing and externalizing conditions both in terms of standard (i.e., the standard deviation of reaction time) and alternative indices that capture low-frequency oscillatory patterns in RT variations over time thought to mark periodic lapses of attention in ADHD. A total of 667 participants (6-12 years old) were classified into non-overlapping diagnostic groups consisting of children with fear disorders (n = 91), distress disorders (n = 56), ADHD (n = 103), oppositional defiant or conduct disorder (ODD/CD; n = 40) and typically developing controls (TDC; n = 377). We used a simple two-choice reaction time task to measure reaction time. The strength of oscillations in RTs across the session was extracted using spectral analyses. Higher RTV was present in ADHD compared to all other disorder groups, effects that were equally strong across all frequency bands. Interestingly, we found that lower RTV to characterize ODD/CD relative to TDC, a finding that was more pronounced at lower frequencies. In general, our data support RTV as a specific marker of ADHD. RT variation across time in ADHD did not show periodicity in a specific frequency band, not supporting that ADHD RTV is the product of spontaneous periodic lapses of attention. Low-frequency oscillations may be particularly useful to differentiate ODD/CD from TDC.

fNIRS Responses in Professional Violinists While Playing Duets: Evidence for Distinct Leader and Follower Roles at the Brain Level.

Music played in ensembles is a naturalistic model to study joint action and leader-follower relationships. Recently, the investigation of the brain underpinnings of joint musical actions has gained attention; however, the cerebral correlates underlying the roles of leader and follower in music performance remain elusive. The present study addressed this question by simultaneously measuring the hemodynamic correlates of functional neural activity elicited during naturalistic violin duet performance using fNIRS. Findings revealed distinct patterns of functional brain activation when musicians played the Violin 2 (follower) than the Violin 1 part (leader) in duets, both compared to solo performance. More specifically, results indicated that musicians playing the Violin 2 part had greater oxy-Hb activation in temporo-parietal (p = 0.02) and somatomotor (p = 0.04) regions during the duo condition in relation to the solo. On the other hand, there were no significant differences in the activation of these areas between duo/solo conditions during the execution of the Violin 1 part (p's > 0.05). These findings suggest that ensemble cohesion during a musical performance may impose particular demands when musicians play the follower position, especially in brain areas associated with the processing of dynamic social information and motor simulation. This study is the first to use fNIRS hyperscanning technology to simultaneously measure the brain activity of two musicians during naturalistic music ensemble performance, opening new avenues for the investigation of brain correlates underlying joint musical actions with multiple subjects in a naturalistic environment.

Using deep autoencoders to identify abnormal brain structural patterns in neuropsychiatric disorders: A large-scale multi-sample study.

Machine learning is becoming an increasingly popular approach for investigating spatially distributed and subtle neuroanatomical alterations in brain-based disorders. However, some machine learning models have been criticized for requiring a large number of cases in each experimental group, and for resembling a "black box" that provides little or no insight into the nature of the data. In this article, we propose an alternative conceptual and practical approach for investigating brain-based disorders which aim to overcome these limitations. We used an artificial neural network known as "deep autoencoder" to create a normative model using structural magnetic resonance imaging data from 1,113 healthy people. We then used this model to estimate total and regional neuroanatomical deviation in individual patients with schizophrenia and autism spectrum disorder using two independent data sets (n = 263). We report that the model was able to generate different values of total neuroanatomical deviation for each disease under investigation relative to their control group (p < .005). Furthermore, the model revealed distinct patterns of neuroanatomical deviations for the two diseases, consistent with the existing neuroimaging literature. We conclude that the deep autoencoder provides a flexible and promising framework for assessing total and regional neuroanatomical deviations in neuropsychiatric populations.

From the Laboratory to the Classroom: The Potential of Functional Near-Infrared Spectroscopy in Educational Neuroscience.

Paralleling two decades of growth in the emergent field known as educational neuroscience is an increasing concern that educational practices and programs should be evidence-based, however, the idea that neuroscience could potentially influence education is controversial. One of the criticisms, regarding applications of the findings produced in this discipline, concerns the artificiality of neuroscientific experiments and the oversimplified nature of the tests used to investigate cognitive processes in educational contexts. The simulations may not account for all of the variables present in real classroom activities. In this study, we aim to get a step closer to the formation of data-supported classroom methodologies by employing functional near-infrared spectroscopy in various experimental paradigms. First, we present two hyperscanning scenarios designed to explore realistic interdisciplinary contexts, i.e., the classroom. In a third paradigm, we present a case study of a single student evaluated with functional near-infrared spectroscopy and mobile eye-tracking glasses. These three experiments are performed to provide proofs of concept for the application of functional near-infrared spectroscopy in scenarios that more closely resemble authentic classroom routines and daily activities. The goal of our study is to explore the potential of this technique in hopes that it offers insights in experimental design to investigate teaching-learning processes during teacher-student interactions.

Network supporting contextual fear learning after dorsal hippocampal damage has increased dependence on retrosplenial cortex.

Hippocampal damage results in profound retrograde, but no anterograde amnesia in contextual fear conditioning (CFC). Although the content learned in the latter have been discussed, alternative regions supporting CFC learning were seldom proposed and never empirically addressed. Here, we employed network analysis of pCREB expression quantified from brain slices of rats with dorsal hippocampal lesion (dHPC) after undergoing CFC session. Using inter-regional correlations of pCREB-positive nuclei between brain regions, we modelled functional networks using different thresholds. The dHPC network showed small-world topology, equivalent to SHAM (control) network. However, diverging hubs were identified in each network. In a direct comparison, hubs in both networks showed consistently higher centrality values compared to the other network. Further, the distribution of correlation coefficients was different between the groups, with most significantly stronger correlation coefficients belonging to the SHAM network. These results suggest that dHPC network engaged in CFC learning is partially different, and engage alternative hubs. We next tested if pre-training lesions of dHPC and one of the new dHPC network hubs (perirhinal, Per; or disgranular retrosplenial, RSC, cortices) would impair CFC. Only dHPC-RSC, but not dHPC-Per, impaired CFC. Interestingly, only RSC showed a consistently higher centrality in the dHPC network, suggesting that the increased centrality reflects an increased functional dependence on RSC. Our results provide evidence that, without hippocampus, the RSC, an anatomically central region in the medial temporal lobe memory system might support CFC learning and memory.

A common representation of time across visual and auditory modalities.

Humans' and non-human animals' ability to process time on the scale of milliseconds and seconds is essential for adaptive behaviour. A central question of how brains keep track of time is how specific temporal information across different sensory modalities is. In the present study, we show that encoding of temporal intervals in auditory and visual modalities are qualitatively similar. Human participants were instructed to reproduce intervals in the range from 750 ms to 1500 ms marked by auditory or visual stimuli. Our behavioural results suggest that, although participants were more accurate in reproducing intervals marked by auditory stimuli, there was a strong correlation in performance between modalities. Using multivariate pattern analysis in scalp EEG, we show that activity during late periods of the intervals was similar within and between modalities. Critically, we show that a multivariate pattern classifier was able to accurately predict the elapsed interval, even when trained on an interval marked by a stimulus of a different sensory modality. Taken together, our results suggest that, while there are differences in the processing of intervals marked by auditory and visual stimuli, they also share a common neural representation.

Predictive saccades in children and adults: A combined fMRI and eye tracking study.

Saccades were assessed in 21 adults (age 24 years, SD = 4) and 15 children (age 11 years, SD = 1), using combined functional magnetic resonance imaging (fMRI) and eye-tracking. Subjects visually tracked a point on a horizontal line in four conditions: time and position predictable task (PRED), position predictable (pPRED), time predictable (tPRED) and visually guided saccades (SAC). Both groups in the PRED but not in pPRED, tPRED and SAC produced predictive saccades with latency below 80 ms. In task versus group comparisons, children's showed less efficient learning compared to adults for predictive saccades (adults = 48%, children = 34%, p = 0.05). In adults brain activation was found in the frontal and occipital regions in the PRED, in the intraparietal sulcus in pPRED and in the frontal eye field, posterior intraparietal sulcus and medial regions in the tPRED task. Group-task interaction was found in the supplementary eye field and visual cortex in the PRED task, and the frontal cortex including the right frontal eye field and left frontal pole, in the pPRED condition. These results indicate that, the basic visuomotor circuitry is present in both adults and children, but fine-tuning of the activation according to the task temporal and spatial demand mature late in child development.

Identification of alterations associated with age in the clustering structure of functional brain networks.

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

Predicting affective valence using cortical hemodynamic signals.

Ascribing affective valence to stimuli or mental states is a fundamental property of human experiences. Recent neuroimaging meta-analyses favor the workspace hypothesis for the neural underpinning of valence, in which both positive and negative values are encoded by overlapping networks but are associated with different patterns of activity. In the present study, we further explored this framework using functional near-infrared spectroscopy (fNIRS) in conjunction with multivariate analyses. We monitored the fronto-temporal and occipital hemodynamic activity of 49 participants during the viewing of affective images (passive condition) and during the imagination of affectively loaded states (active condition). Multivariate decoding techniques were applied to determine whether affective valence is encoded in the cortical areas assessed. Prediction accuracies of 89.90 ± 13.84% and 85.41 ± 14.43% were observed for positive versus neutral comparisons, and of 91.53 ± 13.04% and 81.54 ± 16.05% for negative versus neutral comparisons (passive/active conditions, respectively). Our results are consistent with previous studies using other neuroimaging modalities that support the affective workspace hypothesis and the notion that valence is instantiated by the same network, regardless of whether the affective experience is passively or actively elicited.

Functional near-infrared spectroscopy-based affective neurofeedback: feedback effect, illiteracy phenomena, and whole-connectivity profiles.

Background: Affective neurofeedback constitutes a suitable approach to control abnormal neural activities associated with psychiatric disorders and might consequently relief symptom severity. However, different aspects of neurofeedback remain unclear, such as its neural basis, the performance variation, the feedback effect, among others. Aim: First, we aimed to propose a functional near-infrared spectroscopy (fNIRS)-based affective neurofeedback based on the self-regulation of frontal and occipital networks. Second, we evaluated three different feedback approaches on performance: real, fixed, and random feedback. Third, we investigated different demographic, psychological, and physiological predictors of performance. Approach: Thirty-three healthy participants performed a task whereby an amorphous figure changed its shape according to the elicited affect (positive or neutral). During the task, the participants randomly received three different feedback approaches: real feedback, with no change of the classifier output; fixed feedback, keeping the feedback figure unmodified; and random feedback, where the classifier output was multiplied by an arbitrary value, causing a feedback different than expected by the subject. Then, we applied a multivariate comparison of the whole-connectivity profiles according to the affective states and feedback approaches, as well as during a pretask resting-state block, to predict performance. Results: Participants were able to control this feedback system with 70.00 % ± 24.43 % ( p < 0.01 ) of performance during the real feedback trials. No significant differences were found when comparing the average performances of the feedback approaches. However, the whole functional connectivity profiles presented significant Mahalanobis distances ( p ≪ 0.001 ) when comparing both affective states and all feedback approaches. Finally, task performance was positively correlated to the pretask resting-state whole functional connectivity ( r = 0.512 , p = 0.009 ). Conclusions: Our results suggest that fNIRS might be a feasible tool to develop a neurofeedback system based on the self-regulation of affective networks. This finding enables future investigations using an fNIRS-based affective neurofeedback in psychiatric populations. Furthermore, functional connectivity profiles proved to be a good predictor of performance and suggested an increased effort to maintain task control in the presence of feedback distractors.

Default Mode Network Maturation and Environmental Adversities During Childhood.

Default mode network (DMN) plays a central role in cognition and brain disorders. It has been shown that adverse environmental conditions impact neurodevelopment, but how these conditions impact in DMN maturation is still poorly understood. This article reviews representative neuroimaging functional studies addressing the interactions between DMN development and environmental factors, focusing on early life adversities, a critical period for brain changes. Studies focused on this period of life offer a special challenge: to disentangle the neurodevelopmental connectivity changes from those related to environmental conditions. We first summarized the literature on DMN maturation, providing an overview of both typical and atypical development patterns in childhood and early adolescence. Afterward, we focused on DMN changes associated with chronic exposure to environmental adversities during childhood. This summary suggests that changes in DMN development could be a potential allostatic neural feature associated with an embodiment of environmental circumstances. Finally, we discuss about some key methodological issues that should be considered in paradigms addressing environmental adversities and open questions for future investigations.

Higher similarity in beta topography between tasks than subjects.

We have recently provided evidence for highly idiosyncratic topographic distributions of beta oscillations (as well as slow potentials) across individuals. More recently, by emphasizing the analysis of similarity instead of differences across tasks, we concluded that differences between an attention task and quiet resting may be negligible or at least unsystematic across subjects. Due to the possibility that individual differences could be due to noise in a wide sense or some inherent instability of beta activity, we designed a replication study to explicitly test whether pairs of individuals matched for head size and shape would still present less similar beta topography than each individual between sessions or tasks. We used independent component analysis (ICA) for an exhaustive decomposition of beta activity in a visual attention task and in quiet resting, recorded by 256-channel EEG in 20 subjects, on two separate days. We evaluated whether each ICA component obtained in one task and in one given individual could be explained by a linear regression model based on the topographic patterns of the complementary task (correlation between one component with a linear combination of components from complementary conditions), of the same task in a second session and of a matched individual. Results again showed a high topographic similarity between conditions, as previously seen between reasoning and simple visual attention beta correlates. From an overall number of 16 components representing brain activity obtained for the tasks (out of 60 originally computed where the remaining were considered noise), over 92% could satisfactorily be explained by the complementary task. Although the similarity between sessions was significantly smaller than between tasks on each day, the similarity between sessions was statistically higher than that between subjects in a highly significant way. We discuss the possible biases of group spatial averaging and the emphasis on differences as opposed to similarities, and noise in a wide sense, as the main causes of hardly replicable findings on task-related forms of activity and the inconclusive state of a universal functional mapping of cortical association areas.

Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

OBJECTIVE: Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. METHOD: A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. RESULTS: Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. CONCLUSIONS: Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.