Corrigendum: Assessing MR-compatibility of somatosensory stimulation devices: a systematic review on testing methodologies.

[This corrects the article DOI: 10.3389/fnins.2023.1071749.].

Neurofeedback training of executive function in autism spectrum disorder: distinct effects on brain activity levels and compensatory connectivity changes.

BACKGROUND: Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. METHODS: Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. RESULTS: The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. CONCLUSIONS: Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

Functional and structural connectivity success predictors of real-time fMRI neurofeedback targeting DLPFC: Contributions from central executive, salience, and default mode networks.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF), a training method for the self-regulation of brain activity, has shown promising results as a neurorehabilitation tool, depending on the ability of the patient to succeed in neuromodulation. This study explores connectivity-based structural and functional success predictors in an NF n-back working memory paradigm targeting the dorsolateral prefrontal cortex (DLPFC). We established as the NF success metric the linear trend on the ability to modulate the target region during NF runs and performed a linear regression model considering structural and functional connectivity (intrinsic and seed-based) metrics. We found a positive correlation between NF success and the default mode network (DMN) intrinsic functional connectivity and a negative correlation with the DLPFC-precuneus connectivity during the 2-back condition, indicating that success is associated with larger uncoupling between DMN and the executive network. Regarding structural connectivity, the salience network emerges as the main contributor to success. Both functional and structural classification models showed good performance with 77% and 86% accuracy, respectively. Dynamic switching between DMN, salience network and central executive network seems to be the key for neurofeedback success, independently indicated by functional connectivity on the localizer run and structural connectivity data.

Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

A human cortical adaptive mutual inhibition circuit underlying competition for perceptual decision and repetition suppression reversal.

A model based on inhibitory coupling has been proposed to explain perceptual oscillations. This 'adapting reciprocal inhibition' model postulates that it is the strength of inhibitory coupling that determines the fate of competition between percepts. Here, we used an fMRI-based adaptation technique to reveal the influence of neighboring neuronal populations, such as reciprocal inhibition, in motion-selective hMT+/V5. If reciprocal inhibition exists in this region, the following predictions should hold: 1. stimulus-driven response would not simply decrease, as predicted by simple repetition-suppression of neuronal populations, but instead, increase due to the activity from adjacent populations; 2. perceptual decision involving competing representations, should reflect decreased reciprocal inhibition by adaptation; 3. neural activity for the competing percept should also later on increase upon adaptation. Our results confirm these three predictions, showing that a model of perceptual decision based on adapting reciprocal inhibition holds true. Finally, they also show that the net effect of the well-known repetition suppression phenomenon can be reversed by this mechanism.

Neurofeedback-dependent influence of the ventral striatum using a working memory paradigm targeting the dorsolateral prefrontal cortex.

Executive functions and motivation have been established as key aspects for neurofeedback success. However, task-specific influence of cognitive strategies is scarcely explored. In this study, we test the ability to modulate the dorsolateral prefrontal cortex, a strong candidate for clinical application of neurofeedback in several disorders with dysexecutive syndrome, and investigate how feedback contributes to better performance in a single session. Participants of both neurofeedback (n = 17) and sham-control (n = 10) groups were able to modulate DLPFC in most runs (with or without feedback) while performing a working memory imagery task. However, activity in the target area was higher and more sustained in the active group when receiving feedback. Furthermore, we found increased activity in the nucleus accumbens in the active group, compared with a predominantly negative response along the block in participants receiving sham feedback. Moreover, they acknowledged the non-contingency between imagery and feedback, reflecting the impact on motivation. This study reinforces DLPFC as a robust target for neurofeedback clinical implementations and enhances the critical influence of the ventral striatum, both poised to achieve success in the self-regulation of brain activity.

Assessing MR-compatibility of somatosensory stimulation devices: A systematic review on testing methodologies.

Functional magnetic resonance imaging (fMRI) has been extensively used as a tool to map the brain processes related to somatosensory stimulation. This mapping includes the localization of task-related brain activation and the characterization of brain activity dynamics and neural circuitries related to the processing of somatosensory information. However, the magnetic resonance (MR) environment presents unique challenges regarding participant and equipment safety and compatibility. This study aims to systematically review and analyze the state-of-the-art methodologies to assess the safety and compatibility of somatosensory stimulation devices in the MR environment. A literature search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, was performed in PubMed, Scopus, and Web of Science to find original research on the development and testing of devices for somatosensory stimulation in the MR environment. Nineteen records that complied with the inclusion and eligibility criteria were considered. The findings are discussed in the context of the existing international standards available for the safety and compatibility assessment of devices intended to be used in the MR environment. In sum, the results provided evidence for a lack of uniformity in the applied testing methodologies, as well as an in-depth presentation of the testing methodologies and results. Lastly, we suggest an assessment methodology (safety, compatibility, performance, and user acceptability) that can be applied to devices intended to be used in the MR environment. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021257838.

A neural network underlying cognitive strategies related to eating, weight and body image concerns.

Concerns about food intake, weight and body shape can trigger negatively loaded emotions, which may prompt the use of cognitive strategies to regulate these emotional states. A novel fMRI task was developed to assess the neurobehavioral correlates of cognitive strategies related to eating, weight and body image concerns, such as self-criticism, avoidance, rumination, and self-reassurance. Fourteen healthy females were presented audio sentences referring to these conditions and instructed to repeat these internally while engaging their thoughts with the content of food or body images. Participants were asked to report the elicited emotion and rate their performance. All cognitive strategies recruited a network including the inferior and superior frontal gyri, orbitofrontal and anterior cingulate cortex, insula, and dorsal striatum. These brain regions are involved in emotional, reward and inhibitory control processing. Representational similarity analysis revealed distinct patterns of neural responses for each cognitive strategy. Additionally, self-report measures showed that self-criticism was positively associated with superior frontal gyrus (SFG) activation. Self-compassion scores were negatively correlated with activations in the insula and right putamen, while self-reassurance scores were negatively associated with activity in the orbitofrontal cortex. These findings identify a neural network underlying cognitive strategies related to eating, weight and body image concerns, where neurobehavioral correlation patterns depend on the cognitive strategy.

Training the social brain: Clinical and neural effects of an 8-week real-time functional magnetic resonance imaging neurofeedback Phase IIa Clinical Trial in Autism.

LAY ABSTRACT: Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.

Volitional Modulation of the Left DLPFC Neural Activity Based on a Pain Empathy Paradigm-A Potential Novel Therapeutic Target for Pain.

The ability to perceive and feel another person' pain as if it were one's own pain, e.g., pain empathy, is related to brain activity in the "pain-matrix" network. A non-core region of this network in Dorsolateral Prefrontal Cortex (DLPFC) has been suggested as a modulator of the attentional-cognitive dimensions of pain processing in the context of pain empathy. We conducted a neurofeedback experiment using real-time functional magnetic resonance imaging (rt-fMRI-NF) to investigate the association between activity in the left DLPFC (our neurofeedback target area) and the perspective assumed by the participant ("first-person"/"Self" or "third-person"/"Other" perspective of a pain-inducing stimulus), based on a customized pain empathy task. Our main goals were to assess the participants' ability to volitionally modulate activity in their own DLPFC through an imagery task of pain empathy and to investigate into which extent this ability depends on feedback. Our results demonstrate participants' ability to significantly modulate brain activity of the neurofeedback target area for the "first-person"/"Self" and "third-person"/"Other" perspectives. Results of both perspectives show that the participants were able to modulate (with statistical significance) the activity already in the first run of the session, in spite of being naïve to the task and even in the absence of feedback information. Moreover, they improved modulation throughout the session, particularly in the "Self" perspective. These results provide new insights on the role of DLPFC in pain and pain empathy mechanisms and validate the proposed protocol, paving the way for future interventional studies in clinical populations with empathic deficits.

Identification of competing neural mechanisms underlying positive and negative perceptual hysteresis in the human visual system.

Hysteresis is a well-known phenomenon in physics that relates changes in a system with its prior history. It is also part of human visual experience (perceptual hysteresis), and two different neural mechanisms might explain it: persistence (a cause of positive hysteresis), which forces to keep a current percept for longer, and adaptation (a cause of negative hysteresis), which in turn favors the switch to a competing percept early on. In this study, we explore the neural correlates underlying these mechanisms and the hypothesis of their competitive balance, by combining behavioral assessment with fMRI. We used machine learning on the behavioral data to distinguish between positive and negative hysteresis, and discovered a neural correlate of persistence at a core region of the ventral attention network, the anterior insula. Our results add to the understanding of perceptual multistability and reveal a possible mechanistic explanation for the regulation of different forms of perceptual hysteresis.

How much of the BOLD-fMRI signal can be approximated from simultaneous EEG data: relevance for the transfer and dissemination of neurofeedback interventions.

OBJECTIVE: fMRI-based neurofeedback (NF) interventions represent the method of choice for the neuromodulation of localized brain areas. Although we have already validated an fMRI-NF protocol targeting the facial expressions processing network (FEPN), its dissemination is hampered by the economical and logistical constraints of fMRI-NF interventions, which may be however surpassed by transferring it to EEG setups, due to their low cost and portability. One of the major challenges of this procedure is then to reconstruct the BOLD-fMRI signal measured at the FEPN using only EEG signals. Because these types of approaches have been poorly explored so far, here we systematically investigated the extent at which the BOLD-fMRI signal recorded from the FEPN during a fMRI-NF protocol could be reconstructed from the simultaneously recorded EEG signal. APPROACH: Several features from both scalp and source spaces (the latter estimated using continuous EEG source imaging) were extracted and used as predictors in a regression problem using random forests. Furthermore, three different approaches to deal with the hemodynamic delay of the BOLD signal were tested. The resulting models were compared with the only approach already proposed in the literature that uses spectral features and considers different time delays. MAIN RESULTS: The combination of linear and non-linear features (particularly the largest Lyapunov exponent and entropy measures) projected into the source space, spatially filtered by independent component analysis (ICA) and convolved with multiple HRF functions peaking at different latencies, increases significantly the reconstruction accuracy (defined as the correlation between the measured and approximated BOLD signal) from 20% (direct comparison with the method used in the current literature) to 56%. SIGNIFICANCE: With this pipeline, a more accurate reconstruction of the BOLD signal can be obtained, which will positively impact the transfer of fMRI-based neurofeedback interventions to EEG setups, and more importantly, their dissemination and efficacy in modulating the activity of the desired brain areas.

The boundaries of state-space Granger causality analysis applied to BOLD simulated data: A comparative modelling and simulation approach.

BACKGROUND: The analysis of connectivity has become a fundamental tool in human neuroscience. Granger Causality Mapping is a data-driven method that uses Granger Causality (GC) to assess the existence and direction of influence between signals, based on temporal precedence of information. More recently, a theory of Granger causality has been developed for state-space (SS-GC) processes, but little is known about its statistical validation and application on functional magnetic resonance imaging (fMRI) data. NEW METHOD: We explored different multivariate computational frameworks to define the optimal combination for GC estimation. We hypothesized a new heuristic, combining SS-GC with a distinct statistical validation technique, Time Reversed Testing, validating it on synthetic data. We test its performance with a number of experimental parameters, including block structure, sampling frequency, noise and system mean pairwise correlation, using a statistical framework of binary classification. RESULTS: We found that SS-GC with time reversed testing outperforms other frameworks. The results validate the application of SS-GC to generative models. When estimating reliable causal relations, SS-GC returns promising results, especially when considering synthetic data with a high impact of noise and sampling rate. CONCLUSIONS: In this study, we empirically explored the boundaries of SS-GC with time reversed testing, a data-driven causality analysis framework with potential applicability to fMRI data.

Directly Exploring the Neural Correlates of Feedback-Related Reward Saliency and Valence During Real-Time fMRI-Based Neurofeedback.

Introduction: The potential therapeutic efficacy of real-time fMRI Neurofeedback has received increasing attention in a variety of psychological and neurological disorders and as a tool to probe cognition. Despite its growing popularity, the success rate varies significantly, and the underlying neural mechanisms are still a matter of debate. The question whether an individually tailored framework positively influences neurofeedback success remains largely unexplored. Methods: To address this question, participants were trained to modulate the activity of a target brain region, the visual motion area hMT+/V5, based on the performance of three imagery tasks with increasing complexity: imagery of a static dot, imagery of a moving dot with two and with four opposite directions. Participants received auditory feedback in the form of vocalizations with either negative, neutral or positive valence. The modulation thresholds were defined for each participant according to the maximum BOLD signal change of their target region during the localizer run. Results: We found that 4 out of 10 participants were able to modulate brain activity in this region-of-interest during neurofeedback training. This rate of success (40%) is consistent with the neurofeedback literature. Whole-brain analysis revealed the recruitment of specific cortical regions involved in cognitive control, reward monitoring, and feedback processing during neurofeedback training. Individually tailored feedback thresholds did not correlate with the success level. We found region-dependent neuromodulation profiles associated with task complexity and feedback valence. Discussion: Findings support the strategic role of task complexity and feedback valence on the modulation of the network nodes involved in monitoring and feedback control, key variables in neurofeedback frameworks optimization. Considering the elaborate design, the small sample size here tested (N = 10) impairs external validity in comparison to our previous studies. Future work will address this limitation. Ultimately, our results contribute to the discussion of individually tailored solutions, and justify further investigation concerning volitional control over brain activity.

Self-Modulation of Premotor Cortex Interhemispheric Connectivity in a Real-Time Functional Magnetic Resonance Imaging Neurofeedback Study Using an Adaptive Approach.

Recent studies have reported on the feasibility of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) training. Although modulation of blood oxygenation level-dependent signal of single brain regions in rt-fMRI NF is a well established technique, the same does not hold true for modulation of connectivity. Self-modulation of interregional connectivity is a potential alternative in clinical neuroscience applications, since long-range functional dysconnectivity is being increasingly recognized as a mechanism underlying neuropsychiatric disorders. In this study, a framework was designed to train participants to self-regulate, in real time, interhemispheric functional connectivity between bilateral premotor cortices. To this end, participants use a novel adaptive motor imagery task, with gradual frequency variation preventing activity plateaus and subsequent decreases in correlation of activity (three NF runs). Participants were able to upregulate and maintain interhemispheric connectivity using such adaptive approach, as measured by correlation analysis. Modulation was achieved by simultaneous volitional control of activity in premotor areas. Activation patterns in the downregulation condition led to significantly lower correlation values than those observed in the upregulation condition, in the first two NF runs. Comparison between runs with and without feedback showed enhanced activation in key reward, executive function, and cognitive control regions, suggesting NF promotes reward and the development of goal-directed behavior. This proof-of-principle study suggests that functional connectivity feedback can be used for volitional self-modulation of neuronal connectivity. Functional connectivity-based NF could serve as a possible therapeutic tool in diseases related to the impairment of interhemispheric connectivity, particularly in the context to motor training after stroke.

Targeting dynamic facial processing mechanisms in superior temporal sulcus using a novel fMRI neurofeedback target.

The superior temporal sulcus (STS) encompasses a complex set of regions involved in a wide range of cognitive functions. To understand its functional properties, neuromodulation approaches such brain stimulation or neurofeedback can be used. We investigated whether the posterior STS (pSTS), a core region in the face perception and imagery network, could be specifically identified based on the presence of dynamic facial expressions (and not just on simple motion or static face signals), and probed with neurofeedback. Recognition of facial expressions is critically impaired in autism spectrum disorder, making this region a relevant target for future clinical neurofeedback studies. We used a stringent localizer approach based on the contrast of dynamic facial expressions against static neutral faces plus moving dots. The target region had to be specifically responsive to dynamic facial expressions instead of mere motion and/or the presence of a static face. The localizer was successful in selecting this region across subjects. Neurofeedback was then performed, using this region as a target, with two novel feedback rules (mean or derivative-based, using visual or auditory interfaces). Our results provide evidence that a facial expression-selective cluster in pSTS can be identified and may represent a suitable target for neurofeedback approaches, aiming at social and emotional cognition. These findings highlight the presence of a highly selective region in STS encoding dynamic aspects of facial expressions. Future studies should elucidate its role as a mechanistic target for neurofeedback strategies in clinical disorders of social cognition such as autism.

Evidence for distinct levels of neural adaptation to both coherent and incoherently moving visual surfaces in visual area hMT.

Visual adaptation describes the processes by which the visual system alters its operating properties in response to changes in the environment. It is one of the mechanisms controlling visual perceptual bistability - when two perceptual solutions are available - by controlling the duration of each percept. Moving plaids are an example of such ambiguity. They can be perceived as two surfaces sliding incoherently over each other or as a single coherent surface. Here, we investigated, using fMRI, whether activity in the human motion complex (hMT+), a region tightly related to the perceptual integration of visual motion, is modulated by distinct forms of visual adaptation to coherent or incoherent perception of moving plaids. Our hypothesis is that exposure to global coherent or incoherent moving stimuli leads to different levels of measurable adaptation, reflected in hMT+ activity. We found that the strength of the measured visual adaptation effect depended on whether subjects integrated (coherent percept) or segregated (incoherent percept) surface motion signals. Visual motion adaptation was significant both for coherent motion and globally incoherent surface motion. Although not as strong as to the coherent percept, visual adaptation due to the incoherent percept also affects hMT+. This shows that adaptation can contribute to regulate percept duration during visual bistability, with distinct weights, depending on the type of percept. Our findings suggest a link between bistability and adaptation mechanisms, both due to coherent and incoherent motion percepts, but in an asymmetric manner. These asymmetric adaptation weights have strong implications in models of perceptual decision and may explain asymmetry of perceptual interpretation periods.