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.

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.

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.

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.

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.

Some markers of mirroring appear intact in schizophrenia: evidence from mu suppression.

Although schizophrenia is associated with impairments in social cognition, the scope and neural correlates of these disturbances are largely unknown. In this study, we investigated whether schizophrenia patients show impaired functioning of the mirror neuron system (MNS), as indexed by electroencephalographic (EEG) mu (8-13 Hz) suppression, a hypothesized biomarker of MNS activity that is sensitive to the degree of social interaction depicted in visual stimuli. A total of 32 outpatients and 26 healthy controls completed an EEG paradigm that included six action observation or execution conditions that differed in their degrees of social interaction. Participants also completed a validated empathy questionnaire. Across both groups, we found a significant linear increase in mu suppression across the conditions involving greater levels of social engagement and interaction, but no significant group or interaction effects. Patients self-reported diminished empathic concern and perspective taking, which showed some moderate relations to mu suppression levels. Thus, the schizophrenia group showed generally intact modulation of MNS functioning at the electrophysiological level, despite self-reporting empathic disturbances. The disturbances commonly seen on self-report, performance, and neuroimaging measures of mentalizing in schizophrenia may largely reflect difficulties with higher-level inferential processes about others' emotions, rather than a basic incapacity to share in these experiences.

Mirroring activity in the brain and movement determinant in the Rorschach test.

Human movement (M) responses to the Rorschach are related to cognitive sophistication, creativity, and empathy. Recent studies also link Ms to EEG-mu suppression, an index of mirroring activity in the brain. In this article, we further investigate the link between Ms and mu suppression by testing some clinical interpretative distinctions. Previously collected EEG data recorded during the administration of the Rorschach were reanalyzed. We hypothesized that (a) among several responses investigated, only M would be associated with mu suppression, and (b) Ms with active movement, ordinary form quality, or whole human figures would be most strongly associated with mu suppression. Hypothesis 1 was fully confirmed, thus supporting that the traditional interpretation of M has a neurobiological foundation. Hypothesis 2 was partially confirmed; that is, active Ms were associated with mu suppression more strongly than passive Ms (p < .05), but no other significant differences emerged. Clinical implications are discussed.

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.

Audio-visual facilitation of the mu rhythm.

Previous studies demonstrate that perception of action presented audio-visually facilitates greater mirror neuron system (MNS) activity in humans (Kaplan and Iacoboni in Cogn Process 8(2):103-113, 2007) and non-human primates (Keysers et al. in Exp Brain Res 153(4):628-636, 2003) than perception of action presented unimodally. In the current study, we examined whether audio-visual facilitation of the MNS can be indexed using electroencephalography (EEG) measurement of the mu rhythm. The mu rhythm is an EEG oscillation with peaks at 10 and 20 Hz that is suppressed during the execution and perception of action and is speculated to reflect activity in the premotor and inferior parietal cortices as a result of MNS activation (Pineda in Behav Brain Funct 4(1):47, 2008). Participants observed experimental stimuli unimodally (visual-alone or audio-alone) or bimodally during randomized presentations of two hands ripping a sheet of paper, and a control video depicting a box moving up and down. Audio-visual perception of action stimuli led to greater event-related desynchrony (ERD) of the 8-13 Hz mu rhythm compared to unimodal perception of the same stimuli over the C3 electrode, as well as in a left central cluster when data were examined in source space. These results are consistent with Kaplan and Iacoboni's (in Cogn Process 8(2):103-113, 2007), findings that indicate audio-visual facilitation of the MNS; our left central cluster was localized approximately 13.89 mm away from the ventral premotor cluster identified in their fMRI study, suggesting that these clusters originate from similar sources. Consistency of results in electrode space and component space support the use of ICA as a valid source localization tool.

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.

Deferred primary anastomosis versus diversion in patients with severe secondary peritonitis managed with staged laparotomies.

BACKGROUND: There is inconclusive data on whether critically ill individuals with severe secondary peritonitis requiring multiple staged laparotomies may became eligible candidates for deferred primary anastomoses (DPA). We sought to compare a protocol for DPA against a protocol for diversion in severely ill critical patients with intra-abdominal sepsis. METHODS: A retrospective cohort study was performed examining 112 patients admitted through an ICU between 2002 and 2006, with diagnosis of secondary peritonitis and managed with staged laparotomies whom required small- or large-bowel segment resections. Patients were categorized and compared according to the surgical treatment necessitated to resolve the secondary peritonitis (DPA versus diversion). Outcome measures were days on mechanical ventilation, days required in ICU, days required in hospital, incidence of fistulas/leakages, acute respiratory distress syndrome (ARDS), and mortality. RESULTS: There were 34 patients subjected to DPA and 78 to diversion. Fistulas/leakages developed in three patients (8.8%) with DPA and four patients (5.1%) with diversion (p = 0.359). ARDS was present in 6 patients (17.6%) with DPA and 24 patients (30.8%) with diversion (p = 0.149). There were 30 patients (88.2%) with DPA and 65 patients (83.3%) with diversion discharged alive (p = 0.51). There were not statistical significant differences between groups among survivors regarding hospital length of stay, ICU length of stay, and days on mechanical ventilation. CONCLUSIONS: We did not find significant differences in morbidity or mortality when we compared DPA versus diversion surgical treatment. It is feasible to perform a primary anastomosis in critically ill patients with severe secondary peritonitis managed with staged laparotomies.

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.

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.

Modulation of mu suppression in children with autism spectrum disorders in response to familiar or unfamiliar stimuli: the mirror neuron hypothesis.

In an early description of the mu rhythm, Gastaut and Bert [Gastaut, H. J., & Bert, J. (1954). EEG changes during cinematographic presentation. Clinical Neurophysiology, 6, 433-444] noted that it was blocked when an individual identified himself with an active person on the screen, suggesting that it may be modulated by the degree to which the individual can relate to the observed action. Additionally, multiple recent studies suggest that the mirror neurons system (MNS) is impaired in individuals with autism spectrum disorders (ASD), which may affect their ability to relate to others. The current study aimed to investigate MNS sensitivity by examining mu suppression to familiarity, i.e., the degree to which the observer is able to identify with the actor on the screen by using familiar versus unfamiliar actors. The participants viewed four 80s videos that included: (1) stranger: an unfamiliar hand performing a grasping action; (2) familiar: the child's guardian or sibling's hand performing the same action; (3) own: the participant's own hand performing the same action; (4) bouncing balls: two balls moving vertically toward and away from each other. The study revealed that mu suppression was sensitive to degree of familiarity. Both typically developing participants and those with ASD showed greater suppression to familiar hands compared to those of strangers. These findings suggest that the MNS responds to observed actions in individuals with ASD, but only when individuals can identify in some personal way with the stimuli.

Sensorimotor cortex as a critical component of an 'extended' mirror neuron system: Does it solve the development, correspondence, and control problems in mirroring?

A core assumption of how humans understand and infer the intentions and beliefs of others is the existence of a functional self-other distinction. At least two neural systems have been proposed to manage such a critical distinction. One system, part of the classic motor system, is specialized for the preparation and execution of motor actions that are self realized and voluntary, while the other appears primarily involved in capturing and understanding the actions of non-self or others. The latter system, of which the mirror neuron system is part, is the canonical action 'resonance' system in the brain that has evolved to share many of the same circuits involved in motor control. Mirroring or 'shared circuit systems' are assumed to be involved in resonating, imitating, and/or simulating the actions of others. A number of researchers have proposed that shared representations of motor actions may form a foundational cornerstone for higher order social processes, such as motor learning, action understanding, imitation, perspective taking, understanding facial emotions, and empathy. However, mirroring systems that evolve from the classic motor system present at least three problems: a development, a correspondence, and a control problem. Developmentally, the question is how does a mirroring system arise? How do humans acquire the ability to simulate through mapping observed onto executed actions? Are mirror neurons innate and therefore genetically programmed? To what extent is learning necessary? In terms of the correspondence problem, the question is how does the observer agent know what the observed agent's resonance activation pattern is? How does the matching of motor activation patterns occur? Finally, in terms of the control problem, the issue is how to efficiently control a mirroring system when it is turned on automatically through observation? Or, as others have stated the problem more succinctly: "Why don't we imitate all the time?" In this review, we argue from an anatomical, physiological, modeling, and functional perspectives that a critical component of the human mirror neuron system is sensorimotor cortex. Not only are sensorimotor transformations necessary for computing the patterns of muscle activation and kinematics during action observation but they provide potential answers to the development, correspondence and control problems.

Tinnitus treatment with customized sounds.

Recent studies have indicated that the pathophysiological basis for tinnitus may be abnormal activity in the auditory areas of the brain rather than aberrant activity in the periphery. Tinnitus-related activity leads to changes in tonotopic representation in auditory cortex. However, such reorganization can be reversed through training-induced changes in the response pattern of cortical neurons. We address this problem by using customized sounds that reproduce the subjective experience to reduce overactive auditory circuits. The results of two preliminary studies indicate that customized sound therapy (CST*) aimed at this central dysfunction reduces tinnitus quickly and safely. Participants described immediate relief, showed changes on the Tinnitus Handicap Questionnaire, and reported changes in hearing threshold within 3 weeks. We also saw changes in the intensity dependence of the auditory N100 in tinnitus patients, supporting the idea that tinnitus reflects a reorganization of tonotopic maps in the auditory cortex. The main correlate of this reorganization was the enhanced contrast between responses to the perceived tinnitus pitch and tones approximately one octave lower. After 3 weeks of CST, the intensity dependence to the tinnitus pitch decreased, making these responses more similar to those from normal subjects responding to tones in the same frequency.

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.

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.