Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training.

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections.

Causal relationships in longitudinal observational data: An integrative modeling approach.

Much research in psychology relies on data from observational studies that traditionally do not allow for causal interpretation. However, a range of approaches in statistics and computational sciences have been developed to infer causality from correlational data. Based on conceptual and theoretical considerations on the integration of interventional and time-restrainment notions of causality, we set out to design and empirically test a new approach to identify potential causal factors in longitudinal correlational data. A principled and representative set of simulations and an illustrative application to identify early-life determinants of cognitive development in a large cohort study are presented. The simulation results illustrate the potential but also the limitations for discovering causal factors in observational data. In the illustrative application, plausible candidates for early-life determinants of cognitive abilities in 5-year-old children were identified. Based on these results, we discuss the possibilities of using exploratory causal discovery in psychological research but also highlight its limits and potential misuses and misinterpretations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Novel Exploratory Graph-Based Analytical Tool for Functional Near-Infrared Spectroscopy in Naturalistic Experiments: An Illustrative Application in Typically Developing Children.

Naturalistic paradigms are being increasingly applied to investigate human brain function. Compared with resting-state and task-based paradigms in neuroimaging, naturalistic stimuli and situations can be potentially more readily translated to daily-life applications. Among neuroimaging modalities, functional near-infrared spectroscopy (fNIRS) is particularly suitable for naturalistic investigations and applications. However, specific and tailored statistical analysis to interrogate brain function using naturalistic fNIRS is warranted. Here, we describe an exploratory graph-centrality-based approach to investigating participants' spatiotemporal similarities from the fNIRS signal. We illustrate the usefulness of our approach in a sample of typically developing children (10 males and 9 females; mean age of 5.2 years old; sd = 0.78) while they watch the Inscapes movie designed for neuroimaging acquisition. A node in the left dorsal prefrontal cortex presented similar responses across children, and those fNIRS responses were in line with scene transitions in the movie stimulus. Our results suggest the feasibility of applying centrality graph-based measures to investigate brain function in naturalistic fNIRS during development.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

Multimodal resting-state connectivity predicts affective neurofeedback performance.

Neurofeedback has been suggested as a potential complementary therapy to different psychiatric disorders. Of interest for this approach is the prediction of individual performance and outcomes. In this study, we applied functional connectivity-based modeling using electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) modalities to (i) investigate whether resting-state connectivity predicts performance during an affective neurofeedback task and (ii) evaluate the extent to which predictive connectivity profiles are correlated across EEG and fNIRS techniques. The fNIRS oxyhemoglobin and deoxyhemoglobin concentrations and the EEG beta and gamma bands modulated by the alpha frequency band (beta-m-alpha and gamma-m-alpha, respectively) recorded over the frontal cortex of healthy subjects were used to estimate functional connectivity from each neuroimaging modality. For each connectivity matrix, relevant edges were selected in a leave-one-subject-out procedure, summed into "connectivity summary scores" (CSS), and submitted as inputs to a support vector regressor (SVR). Then, the performance of the left-out-subject was predicted using the trained SVR model. Linear relationships between the CSS across both modalities were evaluated using Pearson's correlation. The predictive model showed a mean absolute error smaller than 20%, and the fNIRS oxyhemoglobin CSS was significantly correlated with the EEG gamma-m-alpha CSS (r = -0.456, p = 0.030). These results support that pre-task electrophysiological and hemodynamic resting-state connectivity are potential predictors of neurofeedback performance and are meaningfully coupled. This investigation motivates the use of joint EEG-fNIRS connectivity as outcome predictors, as well as a tool for functional connectivity coupling investigation.

Differences in brain activity between fast and slow responses on psychomotor vigilance task: an fNIRS study.

Attention is a basic human function underlying every other cognitive process. It is demonstrated in the functional Magnetic Resonance Imaging literature that frontoparietal networks are involved with attentive performance while default mode networks are involved with inattentive performance. Yet, it is still not clear whether similar results would be found with functional Near-Infrared Spectroscopy. The goal of our study was to investigate differences in hemodynamic activity measured by functional Near-Infrared Spectroscopy between fast and slow responses on a simple sustained attention task both before and after stimulus onset. Thirty healthy adults took part in the study. Our results have shown differences between fast and slow responses only on channels over medial frontal cortex and inferior parietal cortex (p < 0,05). These differences were observed both before and after stimulus presentation. It is discussed that functional Near-Infrared Spectroscopy is a good tool to investigate the frontoparietal network and its relationship with performance in attention tasks; it could be used to further investigate other approaches on attention, such as the dual network model of cognitive control and brain states views based on complex systems analysis; and finally, it could be used to investigate attention in naturalistic settings.

Assessing atypical brain functional connectivity development: An approach based on generative adversarial networks.

Generative Adversarial Networks (GANs) are promising analytical tools in machine learning applications. Characterizing atypical neurodevelopmental processes might be useful in establishing diagnostic and prognostic biomarkers of psychiatric disorders. In this article, we investigate the potential of GANs models combined with functional connectivity (FC) measures to build a predictive neurotypicality score 3-years after scanning. We used a ROI-to-ROI analysis of resting-state functional magnetic resonance imaging (fMRI) data from a community-based cohort of children and adolescents (377 neurotypical and 126 atypical participants). Models were trained on data from neurotypical participants, capturing their sample variability of FC. The discriminator subnetwork of each GAN model discriminated between the learned neurotypical functional connectivity pattern and atypical or unrelated patterns. Discriminator models were combined in ensembles, improving discrimination performance. Explanations for the model's predictions are provided using the LIME (Local Interpretable Model-Agnostic) algorithm and local hubs are identified in light of these explanations. Our findings suggest this approach is a promising strategy to build potential biomarkers based on functional connectivity.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

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.

Closed-loop neurostimulation for affective symptoms and disorders: An overview.

Affective and anxiety disorders are the most prevalent and incident psychiatric disorders worldwide. Therapeutic approaches to these disorders using non-invasive brain stimulation (NIBS) and analogous techniques have been extensively investigated. In this paper, we discuss the combination of NIBS and neurofeedback in closed-loop setups and its application for affective symptoms and disorders. For this, we first provide a rationale for this combination by presenting some of the main original findings of NIBS, with a primary focus on transcranial magnetic stimulation (TMS), and neurofeedback, including protocols based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Then, we provide a scope review of studies combining real-time neurofeedback with NIBS protocols in the so-called closed-loop brain state-dependent neuromodulation (BSDS). Finally, we discuss the concomitant use of TMS and real-time functional near-infrared spectroscopy (fNIRS) as a possible solution to the current limitations of BSDS-based protocols for affective and anxiety disorders.

Subject-independent decoding of affective states using functional near-infrared spectroscopy.

Affective decoding is the inference of human emotional states using brain signal measurements. This approach is crucial to develop new therapeutic approaches for psychiatric rehabilitation, such as affective neurofeedback protocols. To reduce the training duration and optimize the clinical outputs, an ideal clinical neurofeedback could be trained using data from an independent group of volunteers before being used by new patients. Here, we investigated if this subject-independent design of affective decoding can be achieved using functional near-infrared spectroscopy (fNIRS) signals from frontal and occipital areas. For this purpose, a linear discriminant analysis classifier was first trained in a dataset (49 participants, 24.65±3.23 years) and then tested in a completely independent one (20 participants, 24.00±3.92 years). Significant balanced accuracies between classes were found for positive vs. negative (64.50 ± 12.03%, p<0.01) and negative vs. neutral (68.25 ± 12.97%, p<0.01) affective states discrimination during a reactive block consisting in viewing affective-loaded images. For an active block, in which volunteers were instructed to recollect personal affective experiences, significant accuracy was found for positive vs. neutral affect classification (71.25 ± 18.02%, p<0.01). In this last case, only three fNIRS channels were enough to discriminate between neutral and positive affective states. Although more research is needed, for example focusing on better combinations of features and classifiers, our results highlight fNIRS as a possible technique for subject-independent affective decoding, reaching significant classification accuracies of emotional states using only a few but biologically relevant features.

Differences in perceived durations between plausible biological and non-biological stimuli.

Visual motion stimuli can sometimes distort our perception of time. This effect is dependent on the apparent speed of the moving stimulus, where faster stimuli are usually perceived lasting longer than slower stimuli. Although it has been shown that neural and cognitive processing of biological motion stimuli differ from non-biological motion stimuli, no study has yet investigated whether perceived durations of biological stimuli differ from non-biological stimuli across different speeds. Here, a prospective temporal reproduction task was used to assess that question. Biological motion stimuli consisted of a human silhouette running in place. Non-biological motion stimuli consisted of a rectangle moving in a pendular way. Amount and plausibility of movement for each stimulus and frame-rate (speed) were evaluated by an independent group of participants. Although the amount of movement perceived was positively correlated to frame rate both for biological and non-biological stimuli, movie clips involving biological motion stimuli were judged to last longer than non-biological motion stimuli only at frame rates for which movement was rated as plausible. These results suggest that plausible representations of biomechanical movement induce additional temporal distortions to those modulated by increases in stimulus speed. Moreover, most studies reporting neural and cognitive differences in the processing of biological and non-biological motion stimuli acquired neurophysiological data using fMRI. Here, we report differences in the processing of biological and non-biological motion stimuli across different speeds using functional near-infrared spectroscopy (fNIRS), a less costly and portable form of neurophysiological data acquisition.

Resting-state global EEG connectivity predicts depression and anxiety severity.

There is a recent interest in finding neurophysiological biomarkers which will facilitate the diagnosis and understanding of the neural basis of different psychiatric disorders. In this paper, we evaluated the resting-state global EEG connectivity as a potential biomarker for depressive and anxiety symptoms. For this, we evaluated a population of 119 subjects, including 75 healthy subjects and 44 patients with major depressive disorder. We calculated the global connectivity (spectral coherence) in a setup of 60 EEG channels, for six different spectral bands: theta, alpha1, alpha2, beta1, beta2, and gamma. These global connectivity scores were used to train a Support Vector Regressor to predict symptoms measured by the Beck Depression Inventory (BDI) and the Spielberger Trait Anxiety Inventory (TAI). Experiments showed a significant prediction of both symptoms, with a mean absolute error (MAE) of 8.07±6.98 and 11.52±8.7 points, respectively. Among the most discriminating features, the global connectivity in the alpha2 band (10.0-12.0Hz) presented significantly positive Spearman's correlation with the depressive (rho = 0.32, pFDR <0.01), and the anxiety symptoms (rho = 0.26, pFDR<0.01).Clinical relevance-This study demonstrates that EEG global connectivity can be used to predict depression and anxiety symptoms measured by widely used questionnaires.

Embodied concepts, allostasis, and the origin of emotions.

Here we advance the proposal that in addition to the importance of emotion words, the dynamics of allostatic regulation play a central role in emotion concept development. We argue for a comprehensive extension of constructed emotion theory to emotional development. To do so, we emphasize possible mechanisms for emotion concept differentiation that may occur before linguistic and semantic skills necessary for constructing and using abstract concepts are sufficiently developed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Socioeconomic status in children is associated with spontaneous activity in right superior temporal gyrus.

Socioeconomic status (SES) during childhood is a well-documented life-course health determinant. Despite recent advances on characterizing brain structural variance associated with SES during development, how it influences brain's functional organization remains elusive. Associations between SES, an fMRI feature of regional spontaneous activity (fractional amplitude of low frequencies fluctuation, fALFF), and behavioral/emotional problems were investigated in a school-based sample of 655 Brazilian children. A voxel-by-voxel approach was applied in order to map brain regions where fALFF was correlated with SES. Based on compelling previous evidence, we hypothesized that fALFF should be associated with SES in areas involved in language processing or cognitive control. Further, we tested if the spontaneous activity in these mapped areas would also correlated with general, internalizing and externalizing problems. SES of children was found to be positively correlated with spontaneous activity in right superior temporal gyrus. In the exploratory analysis, the fALFF of this area was negatively correlated with the expression of internalizing problems. Extending previous behavioral and structural neuroimaging findings, we report an association between SES and the spontaneous activity of a brain area enrolled in the extended language network. This finding is consistent with the hypothesis that the variability on linguistic environment according to SES lead to different developmental trajectories of functional networks instantiating language.

Correction to: Socioeconomic status in children is associated with spontaneous activity in right superior temporal gyrus.

The original version of this article contained mistakes. The surname of Elisa Brietzke was misspelled as "Brietske".

Beyond the target area: an integrative view of tDCS-induced motor cortex modulation in patients and athletes.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.

Association Between Fractional Amplitude of Low-Frequency Spontaneous Fluctuation and Degree Centrality in Children and Adolescents.

The fractional amplitude of low-frequency fluctuations (fALFFs) of the BOLD signal have been successfully applied as exploratory tools in neuroimaging. This metric has been useful in mapping brain functional changes in many clinical populations. However, little is known about the neurophysiological correlates of fALFF. This study aimed at demonstrating that fALFF is related to local network centrality during childhood and adolescence. The establishment of this relationship is fundamental to provide a more meaningful explanation to previous clinical and neurodevelopmental studies based on fALFF. Our findings show a correlation of ∼0.5 between these two metrics at a group level, which is a finding replicated in four large independent samples. However, when considering the across-subject and intra-subject correlations between the two metrics, the correlation is much lower, probably due to the low signal-to-noise ratio. Moreover, we found that regions with high fALFF and degree centrality overlapped modestly, particularly the posterior cingulate/precuneus and lateral parietal cortices.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

Commute Time as a Method to Explore Brain Functional Connectomes.

Graph theory has been extensively applied to investigate complex brain networks in current neuroscience research. Many metrics derived from graph theory, such as local and global efficiencies, are based on the path length between nodes. These approaches are commonly used in analyses of brain networks assessed by resting-state functional magnetic resonance imaging, although relying on the strong assumption that information flow throughout the network is restricted to the shortest paths. In this study, we propose the utilization of commute time as a tool to investigate regional centrality on the functional connectome. Our initial hypothesis was that an alternative approach that considers alternative routes (such as commute time) could provide further information into the organization of functional networks. However, our empirical findings on the ADHD-200 database suggest that at the group level, the commute time and shortest path are highly correlated. In contrast, at the subject level, we discovered that commute time is much less susceptible to head motion artifacts when compared with metrics based on shortest paths. Given the overall similarity between the measures, we argue that commute time might be advantageous particularly for connectomic studies in populations where motion artifacts are a major issue.