Interpersonal neural synchrony and mental disorders: unlocking potential pathways for clinical interventions.

Introduction: Interpersonal synchronization involves the alignment of behavioral, affective, physiological, and brain states during social interactions. It facilitates empathy, emotion regulation, and prosocial commitment. Mental disorders characterized by social interaction dysfunction, such as Autism Spectrum Disorder (ASD), Reactive Attachment Disorder (RAD), and Social Anxiety Disorder (SAD), often exhibit atypical synchronization with others across multiple levels. With the introduction of the "second-person" neuroscience perspective, our understanding of interpersonal neural synchronization (INS) has improved, however, so far, it has hardly impacted the development of novel therapeutic interventions. Methods: To evaluate the potential of INS-based treatments for mental disorders, we performed two systematic literature searches identifying studies that directly target INS through neurofeedback (12 publications; 9 independent studies) or brain stimulation techniques (7 studies), following PRISMA guidelines. In addition, we narratively review indirect INS manipulations through behavioral, biofeedback, or hormonal interventions. We discuss the potential of such treatments for ASD, RAD, and SAD and using a systematic database search assess the acceptability of neurofeedback (4 studies) and neurostimulation (4 studies) in patients with social dysfunction. Results: Although behavioral approaches, such as engaging in eye contact or cooperative actions, have been shown to be associated with increased INS, little is known about potential long-term consequences of such interventions. Few proof-of-concept studies have utilized brain stimulation techniques, like transcranial direct current stimulation or INS-based neurofeedback, showing feasibility and preliminary evidence that such interventions can boost behavioral synchrony and social connectedness. Yet, optimal brain stimulation protocols and neurofeedback parameters are still undefined. For ASD, RAD, or SAD, so far no randomized controlled trial has proven the efficacy of direct INS-based intervention techniques, although in general brain stimulation and neurofeedback methods seem to be well accepted in these patient groups. Discussion: Significant work remains to translate INS-based manipulations into effective treatments for social interaction disorders. Future research should focus on mechanistic insights into INS, technological advancements, and rigorous design standards. Furthermore, it will be key to compare interventions directly targeting INS to those targeting other modalities of synchrony as well as to define optimal target dyads and target synchrony states in clinical interventions.

Revealing the neurobiology underlying interpersonal neural synchronization with multimodal data fusion.

Humans synchronize with one another to foster successful interactions. Here, we use a multimodal data fusion approach with the aim of elucidating the neurobiological mechanisms by which interpersonal neural synchronization (INS) occurs. Our meta-analysis of 22 functional magnetic resonance imaging and 69 near-infrared spectroscopy hyperscanning experiments (740 and 3721 subjects) revealed robust brain regional correlates of INS in the right temporoparietal junction and left ventral prefrontal cortex. Integrating this meta-analytic information with public databases, biobehavioral and brain-functional association analyses suggested that INS involves sensory-integrative hubs with functional connections to mentalizing and attention networks. On the molecular and genetic levels, we found INS to be associated with GABAergic neurotransmission and layer IV/V neuronal circuits, protracted developmental gene expression patterns, and disorders of neurodevelopment. Although limited by the indirect nature of phenotypic-molecular association analyses, our findings generate new testable hypotheses on the neurobiological basis of INS.

Corrigendum: The Potential of Functional Near-Infrared Spectroscopy-Based Neurofeedback-A Systematic Review and Recommendations for Best Practice.

[This corrects the article DOI: 10.3389/fnins.2020.00594.].

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices.

Major depressive disorder (MDD) is the leading cause of disability worldwide. Neurofeedback training has been suggested as a potential additional treatment option for MDD patients not reaching remission from standard care (i.e., psychopharmacology and psychotherapy). Here we systematically reviewed neurofeedback studies employing electroencephalography, or functional magnetic resonance-based protocols in depressive patients. Of 585 initially screened studies, 24 were included in our final sample (N = 480 patients in experimental and N = 194 in the control groups completing the primary endpoint). We evaluated the clinical efficacy across studies and attempted to group studies according to the control condition categories currently used in the field that affect clinical outcomes in group comparisons. In most studies, MDD patients showed symptom improvement superior to the control group(s). However, most articles did not comply with the most stringent study quality and reporting practices. We conclude with recommendations on best practices for experimental designs and reporting standards for neurofeedback training.

Optical brain imaging and its application to neurofeedback.

Besides passive recording of brain electric or magnetic activity, also non-ionizing electromagnetic or optical radiation can be used for real-time brain imaging. Here, changes in the radiation's absorption or scattering allow for continuous in vivo assessment of regional neurometabolic and neurovascular activity. Besides magnetic resonance imaging (MRI), over the last years, also functional near-infrared spectroscopy (fNIRS) was successfully established in real-time metabolic brain imaging. In contrast to MRI, fNIRS is portable and can be applied at bedside or in everyday life environments, e.g., to restore communication and movement. Here we provide a comprehensive overview of the history and state-of-the-art of real-time optical brain imaging with a special emphasis on its clinical use towards neurofeedback and brain-computer interface (BCI) applications. Besides pointing to the most critical challenges in clinical use, also novel approaches that combine real-time optical neuroimaging with other recording modalities (e.g. electro- or magnetoencephalography) are described, and their use in the context of neuroergonomics, neuroenhancement or neuroadaptive systems discussed.

The Potential of Functional Near-Infrared Spectroscopy-Based Neurofeedback-A Systematic Review and Recommendations for Best Practice.

Background: The effects of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI)-neurofeedback on brain activation and behaviors have been studied extensively in the past. More recently, researchers have begun to investigate the effects of functional near-infrared spectroscopy-based neurofeedback (fNIRS-neurofeedback). FNIRS is a functional neuroimaging technique based on brain hemodynamics, which is easy to use, portable, inexpensive, and has reduced sensitivity to movement artifacts. Method: We provide the first systematic review and database of fNIRS-neurofeedback studies, synthesizing findings from 22 peer-reviewed studies (including a total of N = 441 participants; 337 healthy, 104 patients). We (1) give a comprehensive overview of how fNIRS-neurofeedback training protocols were implemented, (2) review the online signal-processing methods used, (3) evaluate the quality of studies using pre-set methodological and reporting quality criteria and also present statistical sensitivity/power analyses, (4) investigate the effectiveness of fNIRS-neurofeedback in modulating brain activation, and (5) review its effectiveness in changing behavior in healthy and pathological populations. Results and discussion: (1-2) Published studies are heterogeneous (e.g., neurofeedback targets, investigated populations, applied training protocols, and methods). (3) Large randomized controlled trials are still lacking. In view of the novelty of the field, the quality of the published studies is moderate. We identified room for improvement in reporting important information and statistical power to detect realistic effects. (4) Several studies show that people can regulate hemodynamic signals from cortical brain regions with fNIRS-neurofeedback and (5) these studies indicate the feasibility of modulating motor control and prefrontal brain functioning in healthy participants and ameliorating symptoms in clinical populations (stroke, ADHD, autism, and social anxiety). However, valid conclusions about specificity or potential clinical utility are premature. Conclusion: Due to the advantages of practicability and relatively low cost, fNIRS-neurofeedback might provide a suitable and powerful alternative to EEG and fMRI neurofeedback and has great potential for clinical translation of neurofeedback. Together with more rigorous research and reporting practices, further methodological improvements may lead to a more solid understanding of fNIRS-neurofeedback. Future research will benefit from exploiting the advantages of fNIRS, which offers unique opportunities for neurofeedback research.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Real-time fMRI neurofeedback training to improve eating behavior by self-regulation of the dorsolateral prefrontal cortex: A randomized controlled trial in overweight and obese subjects.

Obesity is associated with altered responses to food stimuli in prefrontal brain networks that mediate inhibitory control of ingestive behavior. In particular, activity of the dorsolateral prefrontal cortex (dlPFC) is reduced in obese compared to normal-weight subjects and has been linked to the success of weight-loss dietary interventions. In a randomized controlled trial in overweight/obese subjects, we investigated the effect on eating behavior of volitional up-regulation of dlPFC activity via real-time functional magnetic resonance imaging (fMRI) neurofeedback training. Thirty-eight overweight or obese subjects (BMI 25-40 kg/m2) took part in fMRI neurofeedback training with the aim of increasing activity of the left dlPFC (dlPFC group; n = 17) or of the visual cortex (VC/control group; n = 21). Participants were blinded to group assignment. The training session took place on a single day and included three training runs of six trials of up-regulation and passive viewing. Food appraisal and snack intake were assessed at screening, after training, and in a follow-up session four weeks later. Participants of both groups succeeded in up-regulating activity of the targeted brain area. However, participants of the control group also showed increased left dlPFC activity during up-regulation. Functional connectivity between dlPFC and ventromedial PFC, an area that processes food value, was generally increased during up-regulation compared to passive viewing. At follow-up compared to baseline, both groups rated pictures of high-, but not low-calorie foods as less palatable and chose them less frequently. Actual snack intake remained unchanged but palatability and choice ratings for chocolate cookies decreased after training. We demonstrate that one session of fMRI neurofeedback training enables individuals with increased body weight to up-regulate activity of the left dlPFC. Behavioral effects were observed in both groups, which might have been due to dlPFC co-activation in the control group and, in addition, unspecific training effects. Improved dlPFC-vmPFC functional connectivity furthermore suggested enhanced food intake-related control mechanisms. Neurofeedback training might support therapeutic strategies aiming at improved self-control in obesity, although the respective contributions of area-specific mechanisms and general regulation effects are in need of further investigation.