Author Correction: Closed-loop brain training: the science of neurofeedback.

In this article, the affiliation for Mohit Rana was incorrectly listed as the Institute for Biological and Medical Engineering, Department of Psychiatry, and Section of Neuroscience, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860 Hernán Briones, piso 2, Macul 782-0436, Santiago, Chile. The listed affiliation should have been the following: Departamento de Psiquiatría, Escuela de Medicina, Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago, Chile; and the Laboratory for Brain-Machine Interfaces and Neuromodulation, Pontificia Universidad Católica de Chile, Santiago, Chile. An acknowledgement to Mohit Rana's funding source was also missing. The following sentence should have been included in the acknowledgments section: M.R. is supported by a Fondecyt postdoctoral fellowship (project no. 3100648).

"Your Thoughts are (were) Free!": Brain-Computer-Interfaces, Neurofeedback, Detection of Deception, and the Future of Mind-Reading.

This review describes the historical developement and rationale of clinically relevant research on neurophysiological "mind reading" paradims: Brain- Computer-Interfaces, detection of deception, brain stimulation and neurofeedback and the clinical applications in drug resistant epilepsy, chronic stroke, and communication with paralyzed locked-in persons. The emphasis lies on completely locked-in patients with amyotrophic lateral sclerosis using non-invasive and invasive brain computer interfaces and neurofeedback to restore verbal communication with the social environment. In the second part of the article we argue that success and failure of neurophysiological "mind reading" paradigms may be explained with a motor theory of thinking and emotion in combination with learning theory. The ethical implications of brain computer interface and neurofeedback approaches, particularly for severe chronic paralysis and loss of communication diseases and decisions on hastened death and euthanasia are discussed.

On the extraction of purely motor EEG neural correlates during an upper limb visuomotor task.

Deciphering and analyzing the neural correlates of different movements from the same limb using electroencephalography (EEG) would represent a notable breakthrough in the field of sensorimotor neurophysiology. Functional movements involve concurrent posture co-ordination and head and eye movements, which create electrical activity that affects EEG recordings. In this paper, we revisit the identification of brain signatures of different reaching movements using EEG and present, test, and validate a protocol to separate the effect of head and eye movements from a reaching task-related visuomotor brain activity. Ten healthy participants performed reaching movements under two different conditions: avoiding head and eye movements and moving with no constrains. Reaching movements can be identified from EEG with unconstrained eye and head movement, whereas the discriminability of the signals drops to chance level otherwise. These results show that neural patterns associated with different arm movements could only be extracted from EEG if the eye and head movements occurred concurrently with the task, polluting the recordings. Although these findings do not imply that brain correlates of reaching directions cannot be identified from EEG, they show the consequences that ignoring these events can have in any EEG study that includes a visuomotor task.

A Meditation Based Cognitive Therapy (HMBCT) for Primary Insomnia: A Treatment Feasibility Pilot Study.

Previous research has indicated a critical need for cost-effective alternative therapies. The present pilot study aimed to evaluate a novel, cost-effective therapy for treating insomnia. The study employed a randomized controlled trial with two groups: therapy and control. Participants were screened using research diagnostic criteria for insomnia recommended by the American Academy of Sleep Medicine (AASM) before undergoing simple randomization. The study included participants from Hindu, Muslim, and Christian faiths who were assigned to either the therapy group (Hare Krishna Mantra Based Cognitive Therapy: HMBCT) or the non-therapy group (control with relaxing music). Both groups underwent six weeks of treatment with traditional cognitive-behavioral therapy techniques, including stimulus control, sleep restriction, and sleep hygiene. Each week, participants in the therapy group received six 45-minute sessions of HMBCT in the evening and were asked to practice the therapy in the evening of the day of sleep recording. Sleep quality was assessed using behavioral measures, sleep logs, and polysomnography recordings before and after the six-week treatment period. There was a one-week period before and after the six weeks when no treatment was provided. Results showed that HMBCT significantly improved sleep quality measures, including a 61% reduction in Epworth Sleepiness Scale (ESS) scores and an 80% reduction in Insomnia Severity Index (ISI) scores. Participants did not take any sleep-inducing medication during the study. These findings suggest that adding mantra chanting to traditional cognitive-behavioral therapy may improve sleep quality.

Closed-loop brain training: the science of neurofeedback.

Neurofeedback is a psychophysiological procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation. Learning control over specific neural substrates has been shown to change specific behaviours. As a progenitor of brain-machine interfaces, neurofeedback has provided a novel way to investigate brain function and neuroplasticity. In this Review, we examine the mechanisms underlying neurofeedback, which have started to be uncovered. We also discuss how neurofeedback is being used in novel experimental and clinical paradigms from a multidisciplinary perspective, encompassing neuroscientific, neuroengineering and learning-science viewpoints.

Psychophysiological treatment of chronic tinnitus: A review.

Subjective chronic tinnitus consists of a more or less continuous perception of sound in the absence of a corresponding acoustic source, which can lead to various psychological problems like depression, anxiety, attentional deficits and sleep disturbances. The prevalence is 10%-15% of the general population. Various therapy and management options have been proposed, but outcomes vary, and no generally accepted cure exists. In this review, the coherence of the most frequently used aetiological models shall be evaluated, and the efficacy of several treatment options will be discussed. With respect to tinnitus treatments, we focus on controlled studies and meta-analyses. Although there are some therapies that outweigh placebo effects such as cognitive behavioural therapy, neurofeedback or neuromodulation techniques, they mainly target secondary symptoms and not the tinnitus tone itself. Furthermore, positive treatment effects only seem to last for a limited period of time. We conclude that long-lasting combination therapies such as neurofeedback of auditory cortex inhibitory EEG signatures, cognitive therapy and sound-tactile stimulation may provide more efficient outcomes if they target the intensity of the tinnitus tone itself and not only secondary psychological symptoms.

Neuropsychological and neurophysiological aspects of brain-computer-interface (BCI) control in paralysis.

Brain-computer interfaces (BCIs) aim to help paralysed patients to interact with their environment by controlling external devices using brain activity, thereby bypassing the dysfunctional motor system. Some neuronal disorders, such as amyotrophic lateral sclerosis (ALS), severely impair the communication capacity of patients. Several invasive and non-invasive brain-computer interfaces (BCIs), most notably using electroencephalography (EEG), have been developed to provide a means of communication to paralysed patients. However, except for a few reports, all available BCI literature for the paralysed (mostly ALS patients) describes patients with intact eye movement control, i.e. patients in a locked-in state (LIS) but not a completely locked-in state (CLIS). In this article we will discuss: (1) the fundamental neuropsychological learning factors and neurophysiological factors determining BCI performance in clinical applications; (2) the difference between LIS and CLIS; (3) recent development in BCIs for communication with patients in the completely locked-in state; (4) the effect of BCI-based communication on emotional well-being and quality of life; and (5) the outlook and the methodology needed to provide a means of communication for patients who have none. Thus, we present an overview of available studies and recent results and try to anticipate future developments which may open new doors for BCI communication with the completely paralysed.

Correction: Brain-Computer Interface-Based Communication in the Completely Locked-In State.

[This corrects the article DOI: 10.1371/journal.pbio.1002593.].

Brain oscillatory activity as a biomarker of motor recovery in chronic stroke.

In the present work, we investigated the relationship of oscillatory sensorimotor brain activity to motor recovery. The neurophysiological data of 30 chronic stroke patients with severe upper-limb paralysis are the basis of the observational study presented here. These patients underwent an intervention including movement training based on combined brain-machine interfaces and physiotherapy of several weeks recorded in a double-blinded randomized clinical trial. We analyzed the alpha oscillations over the motor cortex of 22 of these patients employing multilevel linear predictive modeling. We identified a significant correlation between the evolution of the alpha desynchronization during rehabilitative intervention and clinical improvement. Moreover, we observed that the initial alpha desynchronization conditions its modulation during intervention: Patients showing a strong alpha desynchronization at the beginning of the training improved if they increased their alpha desynchronization. Patients showing a small alpha desynchronization at initial training stages improved if they decreased it further on both hemispheres. In all patients, a progressive shift of desynchronization toward the ipsilesional hemisphere correlates significantly with clinical improvement regardless of lesion location. The results indicate that initial alpha desynchronization might be key for stratification of patients undergoing BMI interventions and that its interhemispheric balance plays an important role in motor recovery.

Brain-Computer Interface-Based Communication in the Completely Locked-In State.

Despite partial success, communication has remained impossible for persons suffering from complete motor paralysis but intact cognitive and emotional processing, a state called complete locked-in state (CLIS). Based on a motor learning theoretical context and on the failure of neuroelectric brain-computer interface (BCI) communication attempts in CLIS, we here report BCI communication using functional near-infrared spectroscopy (fNIRS) and an implicit attentional processing procedure. Four patients suffering from advanced amyotrophic lateral sclerosis (ALS)-two of them in permanent CLIS and two entering the CLIS without reliable means of communication-learned to answer personal questions with known answers and open questions all requiring a "yes" or "no" thought using frontocentral oxygenation changes measured with fNIRS. Three patients completed more than 46 sessions spread over several weeks, and one patient (patient W) completed 20 sessions. Online fNIRS classification of personal questions with known answers and open questions using linear support vector machine (SVM) resulted in an above-chance-level correct response rate over 70%. Electroencephalographic oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication despite occasional differences between the physiological signals representing a "yes" or "no" response. However, electroencephalogram (EEG) changes in the theta-frequency band correlated with inferior communication performance, probably because of decreased vigilance and attention. If replicated with ALS patients in CLIS, these positive results could indicate the first step towards abolition of complete locked-in states, at least for ALS.

Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke.

Upper limb motor deficits in severe stroke survivors often remain unresolved over extended time periods. Novel neurotechnologies have the potential to significantly support upper limb motor restoration in severely impaired stroke individuals. Here, we review recent controlled clinical studies and reviews focusing on the mechanisms of action and effectiveness of single and combined technology-aided interventions for upper limb motor rehabilitation after stroke, including robotics, muscular electrical stimulation, brain stimulation and brain computer/machine interfaces. We aim at identifying possible guidance for the optimal use of these new technologies to enhance upper limb motor recovery especially in severe chronic stroke patients. We found that the current literature does not provide enough evidence to support strict guidelines, because of the variability of the procedures for each intervention and of the heterogeneity of the stroke population. The present results confirm that neurotechnology-aided upper limb rehabilitation is promising for severe chronic stroke patients, but the combination of interventions often lacks understanding of single intervention mechanisms of action, which may not reflect the summation of single intervention's effectiveness. Stroke rehabilitation is a long and complex process, and one single intervention administrated in a short time interval cannot have a large impact for motor recovery, especially in severely impaired patients. To design personalized interventions combining or proposing different interventions in sequence, it is necessary to have an excellent understanding of the mechanisms determining the effectiveness of a single treatment in this heterogeneous population of stroke patients. We encourage the identification of objective biomarkers for stroke recovery for patients' stratification and to tailor treatments. Furthermore, the advantage of longitudinal personalized trial designs compared to classical double-blind placebo-controlled clinical trials as the basis for precise personalized stroke rehabilitation medicine is discussed. Finally, we also promote the necessary conceptual change from 'one-suits-all' treatments within in-patient clinical rehabilitation set-ups towards personalized home-based treatment strategies, by adopting novel technologies merging rehabilitation and motor assistance, including implantable ones.

Open Software/Hardware Platform for Human-Computer Interface Based on Electrooculography (EOG) Signal Classification.

Electrooculography (EOG) signals have been widely used in Human-Computer Interfaces (HCI). The HCI systems proposed in the literature make use of self-designed or closed environments, which restrict the number of potential users and applications. Here, we present a system for classifying four directions of eye movements employing EOG signals. The system is based on open source ecosystems, the Raspberry Pi single-board computer, the OpenBCI biosignal acquisition device, and an open-source python library. The designed system provides a cheap, compact, and easy to carry system that can be replicated or modified. We used Maximum, Minimum, and Median trial values as features to create a Support Vector Machine (SVM) classifier. A mean of 90% accuracy was obtained from 7 out of 10 subjects for online classification of Up, Down, Left, and Right movements. This classification system can be used as an input for an HCI, i.e., for assisted communication in paralyzed people.

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.

Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch-regulation in nonsingers.

While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch-matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch-matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx-S1 iTBS enhanced pitch accuracy (50-250 ms after sound onset) and pitch stability (>250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx-S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic-proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx-S1 in vocal pitch regulation during singing.

Spatial characteristics of spontaneous and stimulus-induced individual functional connectivity networks in severe disorders of consciousness.

BACKGROUND: Functional connectivity (fcMRI) analyses of resting state functional magnetic resonance imaging (fMRI) data revealed substantial differences between states of consciousness. The underlying cause-effect linkage, however, remains unknown to the present day. The aim of this study was to examine the relationship between fcMRI measures and Disorders of Consciousness (DOC) in resting state and under adequate stimulation. METHODS AND FINDINGS: fMRI data from thirteen patients with unresponsive wakefulness syndrome, eight patients in minimally conscious state, and eleven healthy controls were acquired in rest and during the application of nociceptive and emotional acoustic stimuli. We compared spatial characteristics and anatomical topography of seed-based fcMRI networks on group and individual levels. The anatomical topography of fcMRI networks of patients was altered in all three conditions as compared with healthy controls. Spread and distribution of individual fcMRI networks, however, differed significantly between patients and healthy controls in stimulation conditions only. The exploration of individual metric values identified two patients whose spatial metrics did not deviate from metric distributions of healthy controls in a statistically meaningful manner. CONCLUSIONS: These findings suggest that the disturbance of consciousness in DOC is related to deficits in global topographical network organization rather than a principal inability to establish long-distance connections. In addition, the results question the claim that task-free measurements are particularly valuable as a tool for individual diagnostics in severe neurological disorders. Further studies comparing connectivity indices with outcome of DOC patients are needed to determine the clinical relevance of spatial metrics and stimulation paradigms for individual diagnosis, prognosis and treatment in DOC.

Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

Learned control of inter-hemispheric connectivity: Effects on bimanual motor performance.

Bimanual movements involve the interactions between both primary motor cortices. These interactions are assumed to involve phase-locked oscillatory brain activity referred to as inter-hemispheric functional coupling. So far, inter-hemispheric functional coupling has been investigated as a function of motor performance. These studies report mostly a negative correlation between the performance in motor tasks and the strength of functional coupling. However, correlation might not reflect a causal relationship. To overcome this limitation, we opted for an alternative approach by manipulating the strength of inter-hemispheric functional coupling and assessing bimanual motor performance as a dependent variable. We hypothesize that an increase/decrease of functional coupling deteriorates/facilitates motor performance in an out-of-phase bimanual finger-tapping task. Healthy individuals were trained to volitionally regulate functional coupling in an operant conditioning paradigm using real-time magnetoencephalography neurofeedback. During operant conditioning, two discriminative stimuli were associated with upregulation and downregulation of functional coupling. Effects of training were assessed by comparing motor performance prior to (pre-test) and after the training (post-test). Participants receiving contingent feedback learned to upregulate and downregulate functional coupling. Comparing motor performance, as indexed by the ratio of tapping speed for upregulation versus downregulation trials, no change was found in the control group between pre- and post-test. In contrast, the group receiving contingent feedback evidenced a significant decrease of the ratio implicating lower tapping speed with stronger functional coupling. Results point toward a causal role of inter-hemispheric functional coupling for the performance in bimanual tasks. Hum Brain Mapp 38:4353-4369, 2017. © 2017 Wiley Periodicals, Inc.

Volitional regulation of brain responses to food stimuli in overweight and obese subjects: A real-time fMRI feedback study.

Obese subjects who achieve weight loss show increased functional connectivity between dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC), key areas of executive control and reward processing. We investigated the potential of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training to achieve healthier food choices by enhancing self-control of the interplay between these brain areas. We trained eight male individuals with overweight or obesity (age: 31.8 ± 4.4 years, BMI: 29.4 ± 1.4 kg/m2) to up-regulate functional connectivity between the dlPFC and the vmPFC by means of a four-day rt-fMRI neurofeedback protocol including, on each day, three training runs comprised of six up-regulation and six passive viewing trials. During the up-regulation runs of the four training days, participants successfully learned to increase functional connectivity between dlPFC and vmPFC. In addition, a trend towards less high-calorie food choices emerged from before to after training, which however was associated with a trend towards increased covertly assessed snack intake. Findings of this proof-of-concept study indicate that overweight and obese participants can increase functional connectivity between brain areas that orchestrate the top-down control of appetite for high-calorie foods. Neurofeedback training might therefore be a useful tool in achieving and maintaining weight loss.