Brain-Computer Interface Training of mu EEG Rhythms in Intellectually Impaired Children with Autism: A Feasibility Case Series.

Prior studies show that neurofeedback training (NFT) of mu rhythms improves behavior and EEG mu rhythm suppression during action observation in children with autism spectrum disorder (ASD). However, intellectually impaired persons were excluded because of their behavioral challenges. We aimed to determine if intellectually impaired children with ASD, who were behaviorally prepared to take part in a mu-NFT study using conditioned auditory reinforcers, would show improvements in symptoms and mu suppression following mu-NFT. Seven children with ASD (ages 6-8; mean IQ 70.6 ± 7.5) successfully took part in mu-NFT. Four cases demonstrated positive learning trends (hit rates) during mu-NFT (learners), and three cases did not (non-learners). Artifact-creating behaviors were present during tests of mu suppression for all cases, but were more frequent in non-learners. Following NFT, learners showed behavioral improvements and were more likely to show evidence of a short-term increase in mu suppression relative to non-learners who showed little to no EEG or behavior improvements. Results support mu-NFT's application in some children who otherwise may not have been able to take part without enhanced behavioral preparations. Children who have more limitations in demonstrating learning during NFT, or in providing data with relatively low artifact during task-dependent EEG tests, may have less chance of benefiting from mu-NFT. Improving the identification of ideal mu-NFT candidates, mu-NFT learning rates, source analyses, EEG outcome task performance, population-specific artifact-rejection methods, and the theoretical bases of NFT protocols, could aid future BCI-based, neurorehabilitation efforts.

Neural perspectives on morality due to beguiling mechanisms.

We consider deception an example of behavior that challenges traditional explanations of moral behavior. Beguiling mechanisms, by which we mean deceptiveness with charming seduction for diversion, subtly influence moral sensitivity and judgment in moral dilemma situations. The duality of beguiling mechanisms is important to grasp, including how they relate to the ambiguity of situations. Further, we view moral behavior as quasi-adaptive, affectively based, and reliant on the processes of social cognition, arising out of a set of domain-general primitive predispositions that aggregate to produce moral "mindsets" and increasingly complex moral actions. Building on recent theoretical developments, contend that morality involves a complex heterarchical-hierarchical neurological architecture, where activity is dynamically and contextually dependent, as well as dependent on evolved brain structures and early life year socialization. We contribute to conceptualizing moral behavior from an integrated modern neural perspective. This provides a balance between moral decisions as situational, emotional, and genetically completed non-conscious processes, and the more traditional view of conscious reasoning. Beguiling mechanisms illustrate an integrative model of morality, consistent with emerging insights from affective and cognitive neuroscience.

The Effect of Modeling Methods on Mirror Neuron Activity and a Motor Skill Acquisition and Retention.

Introduction: Mirror neurons have been suggested as a potential neural mechanism of observational learning. This study aims to investigate the effect of self-modeling, skilled model, and learning model on mu rhythm suppression and golf putting acquisition and retention. Methods: The study was conducted on 45 male volunteer students (aged 19.4±0.37 years) in three experimental groups, self-modeling, skilled, and learning models with six sessions of physical and observational training in three periods of pre-test, acquisition, and retention. In the pre-test, after the initial familiarity with the skill, participants performed 10 golf putting actions while scores were recorded. Then, electrical brain waves in C3, C4, and Cz regions were recorded during the observation of 10 golf putting actions by their group-related models. The acquisition period consisted of golf putting training during six sessions, each consisting of six blocks of 10 trials. Before each training block, participants observed golf putting related to their group 10 times in the form of a video. Acquisition and delayed retention tests were also performed by recording scores of 10 golf putting actions, as well as recording electrical brain waves while observing the skill performed by the related model. Results: Mixed analysis of variance (ANOVA) showed that the mu rhythm suppression in the pre-test was more in the self-modeling group compared to the skilled model and learning model groups, but this suppression was not significantly different in all three groups in the acquisition and retention tests. In putting task variables, all three groups that had no significant difference in the pre-test period made considerable progress in learning the desired skill from the pre-test to the acquisition test, and this progress was somewhat stable until the retention test. Also, both in the acquisition and retention periods, the self-modeling group showed better performance than the other two groups; however, no significant difference was observed between these groups. Conclusion: These results suggest that the model-observer similarity is a crucial factor in modeling interventions and can affect the rate of mu rhythm suppression.

Novel EEG-Based Neurofeedback System Targeting Frontal Gamma Activity of Schizophrenia Patients to Improve Working Memory.

Patients with schizophrenia (SCZ) exhibit working memory (WM) deficits that are associated with deficient dorsal-lateral prefrontal cortical activity, including decreased frontal gamma power. We thus hypothesized that training SCZ patients to increase frontal gamma activity would improve their WM performance. We administered electroencephalographic (EEG) neurofeedback (NFB) to 31 participants with SCZ for 12 weeks (24 sessions), which provides real-time visual and auditory feedback related to frontal gamma activity. The EEG-NFB training significantly improved EEG markers of optimal working memory, e.g., frontal P3 amplitude and gamma power. Based on these promising results, we developed a novel, EEGLAB/MATLAB-based brain-computer interface (BCI) that delivers F3-F4 gamma coherence NFB with a dynamic threshold to SCZ patients randomized in a double-blind, placebo-controlled clinical trial. The BCI significantly increased F3-F4 gamma coherence after 12 weeks (24 sessions) of training, according to data from the first 12 subjects ( n=6 /group) who completed gamma- or placebo-NFB training.

A Systematic Review of the Potential Use of Neurofeedback in Patients With Schizophrenia.

Schizophrenia (SCZ) is a neurodevelopmental disorder characterized by positive symptoms (hallucinations and delusions), negative symptoms (anhedonia, social withdrawal) and marked cognitive deficits (memory, executive function, and attention). Current mainstays of treatment, including medications and psychotherapy, do not adequately address cognitive symptoms, which are essential for everyday functioning. However, recent advances in computational neurobiology have rekindled interest in neurofeedback (NF), a form of self-regulation or neuromodulation, in potentially alleviating cognitive symptoms in patients with SCZ. Therefore, we conducted a systematic review of the literature for NF studies in SCZ to identify lessons learned and to identify steps to move the field forward. Our findings reveal that NF studies to date consist mostly of case studies and small sample, single-group studies. Despite few randomized clinical trials, the results suggest that NF is feasible and that it leads to measurable changes in brain function. These findings indicate early proof-of-concept data that needs to be followed up by larger, randomized clinical trials, testing the efficacy of NF compared to well thought out placebos. We hope that such an undertaking by the field will lead to innovative solutions that address refractory symptoms and improve everyday functioning in patients with SCZ.

Modulation of frontal gamma oscillations improves working memory in schizophrenia.

Schizophrenia is a debilitating mental disorder that is associated with cognitive deficits. Impairments in cognition occur early in the course of illness and are associated with poor functional outcome, but have been difficult to treat with conventional treatments. Recent studies have implicated abnormal neural network dynamics and impaired connectivity in frontal brain regions as possible causes of cognitive deficits. For example, high-frequency, dorsal-lateral prefrontal oscillatory activity in the gamma range (30-50 Hz) is associated with impaired working memory in individuals with schizophrenia.In light of these findings, it may be possible to use EEG neurofeedback (EEG-NFB) to train individuals with schizophrenia to enhance frontal gamma activity to improve working memory and cognition. In a single-group, proof-of-concept study, 31 individuals with schizophrenia received 12 weeks of twice weekly EEG-NFB to enhance frontal gamma band response. EEG-NFB was well-tolerated, associated with increased gamma training threshold, and significant increases in frontal gamma power during an n-back working memory task. Additionally, EEG-NFB was associated with significant improvements in n-back performance and working memory, speed of processing, and reasoning and problem solving on neuropsychological tests. Change in gamma power was associated with change in cognition. Significant improvements in psychiatric symptoms were also found. These encouraging findings suggest EEG-NFB targeting frontal gamma activity may provide a novel effective approach to cognitive remediation in schizophrenia, although placebo-controlled trials are needed to assess the effects of non-treatment related factors.

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.

Human Movement Responses to the Rorschach and Mirroring Activity: An fMRI Study.

It has been suggested that the Rorschach human movement (M) response could be associated with an embodied simulation mechanism mediated by the mirror neuron system (MNS). To date, evidence for this hypothesis comes from two electroencephalogram studies and one repetitive transcranial magnetic stimulation study. To provide additional data on this topic, the Rorschach was administered during fMRI to a sample of 26 healthy adult volunteers. Activity in MNS-related brain areas temporally associated with M responses was compared with such activity for other, non-M Rorschach responses. Data analyses focused on MNS regions of interest identified by Neurosynth, a web-based platform for large scale, automated meta-analysis of fMRI data. Consistent with the hypothesis that M responses involve embodied simulation and MNS activity, univariate region of interest analyses showed that production of M responses associated with significantly greater activity in MNS-related brain areas when compared with non-M Rorschach responses. This finding is consistent with the traditional interpretation of the M code.

Improving the performance of virtual crossmatch results by correlating with nationally-performed physical crossmatches: Obtaining additional value from proficiency testing activities.

PURPOSE: When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch. METHOD: DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015. RESULTS: 180 surveys were analyzed. Positive CDC-AHG and flow cytometric crossmatches were associated with MFI greater than 8554 and 2748 respectively for HLA class I, and 6919 and 3707 respectively for class II. Institutional MFI less than 3000 had high positive predictive values (0.98, 0.85, 0.81) for negative direct, AHG, and flow crossmatches, while MFI greater than 8000 had high negative predictive values for a positive direct, AHG, and flow crossmatches (1.00, 1.00, 0.97). CONCLUSION: Review of locally-generated MFI results as part of participating in proficiency testing allow for predictability of crossmatch results against other laboratories, providing a replicable model for other participating centers.

Facilitating Neurofeedback in Children with Autism and Intellectual Impairments Using TAGteach.

Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation.

Autism has been characterized by atypical task-related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience-dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self-regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu-rhythm-based NFT in children with high-functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8-17). During a functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre- vs. post-training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu-rhythm NFT may be beneficial to individuals with ASD.

Effects of repetitive transcranial magnetic stimulation (rTMS) on attribution of movement to ambiguous stimuli and EEG mu suppression.

Recent research suggests that attributing human movement to ambiguous and static Rorschach stimuli (M responses) is associated with EEG mu suppression, and that disrupting the left inferior gyrus (LIFG; a putative area implicated in mirroring activity) decreases the tendency to see human movement when exposed to the Rorschach ambiguous stimuli. The current study aimed to test whether disrupting the LIFG via repetitive transcranial stimulation (rTMS) would decrease both the number of human movement attributions and EEG mu suppression. Each participant was exposed to the Rorschach stimuli twice, i.e., during a baseline condition (without rTMS but with EEG recording) and soon after rTMS (TMS condition with EEG recording). Experimental group (N = 15) was stimulated over the LIFG, while the control group (N = 13) was stimulated over the Vertex. As expected, disrupting the LIFG but not Vertex, decreased the number of M attributions provided by the participants exposed to the Rorschach stimuli, with a significant interaction effect. Unexpectedly, however, rTMS did not significantly influence EEG mu suppression.

Increased risk organ transplantation in the pediatric population.

IRD organs are classified by the Public Health Service to be at above-average risk for harboring human immunodeficiency virus, hepatitis C, and hepatitis B. Traditionally underutilized, there exists even greater reluctance for their use in pediatric patients. We performed a retrospective analysis via the United Network for Organ Sharing database of all pediatric renal and hepatic transplants performed from 2004 to 2008 in the United States. Primary outcomes were patient and graft survival. Proportional hazards regression was performed to control for potentially confounding factors. Waitlist time, organ acceptance rates, and infectious transmissions were analyzed. There were 1830 SRD renal, 92 IRD renal, 1695 SRD hepatic, and 59 IRD hepatic transplants. There were no statistically significant differences in allograft or patient survival in either group. Acceptance rates of IRD organs were lower for kidney (1.5% IRD vs 4.82% SRD) and liver (1.99% IRD vs 4.51% SRD). One transmission of a bloodborne pathogen involving a pediatric recipient out of 7797 unique transplants was reported from 2008 to 2015. IRD organs appear to have equivalent outcomes. Increasing their utilization may improve access to transplant while decreasing wait times and circumventing waitlist morbidity and mortality.

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience.

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research.

Resting State Functional Connectivity MRI among Spectral MEG Current Sources in Children on the Autism Spectrum.

Social and communicative impairments are among the core symptoms of autism spectrum disorders (ASD), and a great deal of evidence supports the notion that these impairments are associated with aberrant functioning and connectivity of various cortical networks. The present study explored the links between sources of MEG amplitude in various frequency bands and functional connectivity MRI in the resting state. The goal of combining these modalities was to use sources of neural oscillatory activity, measured with MEG, as functionally relevant seed regions for a more traditional pairwise fMRI connectivity analysis. We performed a seed-based connectivity analysis on resting state fMRI data, using seed regions derived from frequency-specific amplitude sources in resting state MEG data in the same nine subjects with ASD (10-17 years of age). We then compared fMRI connectivity among these MEG-source-derived regions between participants with autism and typically developing, age-matched controls. We used a source modeling technique designed for MEG data to detect significant amplitude sources in six frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-60 Hz), and high gamma (60-120 Hz). MEG-derived source maps for each participant were co-registered in standard MNI space, and group-level source maps were obtained for each frequency. For each frequency band, the 10 largest clusters resulting from these t-tests were used as regions of interest (ROIs) for the fMRI functional connectivity analysis. Pairwise BOLD signal correlations were obtained between each pair of these ROIs for each frequency band. Each pairwise correlation was compared between the ASD and TD groups using t-tests. We also constrained these pairwise correlations to known network structures, resulting in a follow-up set of correlation matrices specific to each network we considered. Frequency-specific MEG sources had distinct patterns of fMRI resting state functional connectivity in the ASD group, but perhaps the most significant was a finding of hypoconnectivity between many sources of low and high gamma activity. These novel findings suggest that in ASD there are differences in functionally defined networks as shown in previous fMRI studies, as well as between sets of regions defined by magnetoencephalographic neural oscillatory activity.

Effects of intranasal oxytocin on neural processing within a socially relevant neural circuit.

Dysregulation of the Mirror Neuron System (MNS) in schizophrenia (SCZ) may underlie the cognitive and behavioral manifestations of social dysfunction associated with that disorder. In healthy subjects intranasal (IN) oxytocin (OT) improves neural processing in the MNS and is associated with improved social cognition. OT's brain effects can be measured through its modulation of the MNS by suppressing EEG mu-band electrical activity (8-13Hz) in response to motion perception. Although IN OT's effects on social cognition have been tested in SCZ, OT's impact on the MNS has not been evaluated to date. Therefore, we designed a study to investigate the effects of two different OT doses on biological motion-induced mu suppression in SCZ and healthy subjects. EEG recordings were taken after each subject received a single IN administration of placebo, OT-24IU and OT-48IU in randomized order in a double-blind crossover design. The results provide support for OT's regulation of the MNS in both healthy and SCZ subjects, with the optimal dose dependent on diagnostic group and sex of subject. A statistically significant response was seen in SCZ males only, indicating a heightened sensitivity to those effects, although sex hormone related effects cannot be ruled out. In general, OT appears to have positive effects on neural circuitry that supports social cognition and socially adaptive behaviors.

Musical Sequence Learning and EEG Correlates of Audiomotor Processing.

Our motor and auditory systems are functionally connected during musical performance, and functional imaging suggests that the association is strong enough that passive music listening can engage the motor system. As predictive coding constrains movement sequence selections, could the motor system contribute to sequential processing of musical passages? If this is the case, then we hypothesized that the motor system should respond preferentially to passages of music that contain similar sequential information, even if other aspects of music, such as the absolute pitch, have been altered. We trained piano naive subjects with a learn-to play-by-ear paradigm, to play a simple melodic sequence over five days. After training, we recorded EEG of subjects listening to the song they learned to play, a transposed version of that song, and a control song with different notes and sequence from the learned song. Beta band power over sensorimotor scalp showed increased suppression for the learned song, a moderate level of suppression for the transposed song, and no suppression for the control song. As beta power is associated with attention and motor processing, we interpret this as support of the motor system's activity during covert perception of music one can play and similar musical sequences.

An Effective Neurofeedback Intervention to Improve Social Interactions in Children with Autism Spectrum Disorder.

Neurofeedback training (NFT) approaches were investigated to improve behavior, cognition and emotion regulation in children with autism spectrum disorder (ASD). Thirteen children with ASD completed pre-/post-assessments and 16 NFT-sessions. The NFT was based on a game that encouraged social interactions and provided feedback based on imitation and emotional responsiveness. Bidirectional training of EEG mu suppression and enhancement (8-12 Hz over somatosensory cortex) was compared to the standard method of enhancing mu. Children learned to control mu rhythm with both methods and showed improvements in (1) electrophysiology: increased mu suppression, (2) emotional responsiveness: improved emotion recognition and spontaneous imitation, and (3) behavior: significantly better behavior in every-day life. Thus, these NFT paradigms improve aspects of behavior necessary for successful social interactions.

The role of the extended MNS in emotional and nonemotional judgments of human song.

In the present study, we examined the involvement of the extended mirror neuron system (MNS)-specifically, areas that have a strong functional connection to the core system itself-during emotional and nonemotional judgments about human song. We presented participants with audiovisual recordings of sung melodic intervals (two-tone sequences) and manipulated emotion and pitch judgments while keeping the stimuli identical. Mu event-related desynchronization (ERD) was measured as an index of MNS activity, and a source localization procedure was performed on the data to isolate the brain sources contributing to this ERD. We found that emotional judgments of human song led to greater amounts of ERD than did pitch distance judgments (nonemotional), as well as control judgments related to the singer's hair, or pitch distance judgments about a synthetic tone sequence. Our findings support and expand recent research suggesting that the extended MNS is involved to a greater extent during emotional than during nonemotional perception of human action.