"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.

Altered brain dynamics index levels of arousal in complete locked-in syndrome.

Complete locked-in syndrome (CLIS) resulting from late-stage amyotrophic lateral sclerosis (ALS) is characterised by loss of motor function and eye movements. The absence of behavioural indicators of consciousness makes the search for neuronal correlates as possible biomarkers clinically and ethically urgent. EEG-based measures of brain dynamics such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) have been shown to have explanatory power for consciousness and may provide such neuronal indices for patients with CLIS. Here, we validated PLE and LZC (calculated in a dynamic way) as benchmarks of a wide range of arousal states across different reference states of consciousness (e.g., awake, sleep stages, ketamine, sevoflurane). We show a tendency toward high PLE and low LZC, with high intra-subject fluctuations and inter-subject variability in a cohort of CLIS patients with values graded along different arousal states as in our reference data sets. In conclusion, changes in brain dynamics indicate altered arousal in CLIS. Specifically, PLE and LZC are potentially relevant biomarkers to identify or diagnose the arousal level in CLIS and to determine the optimal time point for treatment, including communication attempts.

The hemodynamic initial-dip consists of both volumetric and oxymetric changes reflecting localized spiking activity.

The initial-dip is a transient decrease frequently observed in functional neuroimaging signals, immediately after stimulus onset, believed to originate from a rise in deoxy-hemoglobin (HbR) caused by local neural activity. It has been shown to be more spatially specific than the hemodynamic response, and is believed to represent focal neuronal activity. However, despite being observed in various neuroimaging modalities (such as fMRI, fNIRS, etc), its origins are disputed, and its precise neuronal correlates are unknown. Here we show that the initial-dip is dominated by a decrease in total-hemoglobin (HbT). We also find a biphasic response in deoxy-Hb (HbR), with an early decrease and later rebound. Both the HbT-dip and HbR-rebound were strongly correlated to highly localized spiking activity. However, HbT decreases were always large enough to counter the spiking-induced increase in HbR. We find that the HbT-dip counters spiking induced HbR increases, imposing an upper-limit to HbR concentration in the capillaries. Building on our results, we explore the possibility of active venule dilation (purging) as a possible mechanism for the HbT dip.

Cortical processing during robot and functional electrical stimulation.

Introduction: Like alpha rhythm, the somatosensory mu rhythm is suppressed in the presence of somatosensory inputs by implying cortical excitation. Sensorimotor rhythm (SMR) can be classified into two oscillatory frequency components: mu rhythm (8-13 Hz) and beta rhythm (14-25 Hz). The suppressed/enhanced SMR is a neural correlate of cortical activation related to efferent and afferent movement information. Therefore, it would be necessary to understand cortical information processing in diverse movement situations for clinical applications. Methods: In this work, the EEG of 10 healthy volunteers was recorded while fingers were moved passively under different kinetic and kinematic conditions for proprioceptive stimulation. For the kinetics aspect, afferent brain activity (no simultaneous volition) was compared under two conditions of finger extension: (1) generated by an orthosis and (2) generated by the orthosis simultaneously combined and assisted with functional electrical stimulation (FES) applied at the forearm muscles related to finger extension. For the kinematic aspect, the finger extension was divided into two phases: (1) dynamic extension and (2) static extension (holding the extended position). Results: In the kinematic aspect, both mu and beta rhythms were more suppressed during a dynamic than a static condition. However, only the mu rhythm showed a significant difference between kinetic conditions (with and without FES) affected by attention to proprioception after transitioning from dynamic to static state, but the beta rhythm was not. Discussion: Our results indicate that mu rhythm was influenced considerably by muscle kinetics during finger movement produced by external devices, which has relevant implications for the design of neuromodulation and neurorehabilitation interventions.

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.

Neural substrates of tinnitus severity.

Subjective chronic tinnitus is a prevalent auditory perception characterized by an absence of a corresponding acoustic source. It is often accompanied by hearing deficits and may lead to various psychological problems including sleep disorder, depression and anxiety. To investigate the differential neuronal profile of patients with severe and less severe chronic tinnitus, 34 tinnitus patients were distributed in two groups and their EEG resting state activity was compared. Using standardized Low Resolution Electromagnetic Tomography (sLORETA) a significant and substantial frontal increase in theta wave activity was found in the group with severe tinnitus (p = .013). The correlated severity of depression and anxiety had no influence on the electrophysiological metric. These results support a tinnitus-related global network change in which prefrontal areas are part of a network which exerts a top-down influence on the auditory cortices. The demonstrated slowing of oscillations in the responsible network may constitute a neuronal marker for the prefrontal brain network lacking the capacity to inhibit overexcitation. The magnitude of this influence is linked to the subjective strength of the tinnitus distress.

A Novel Patient-Tailored, Cumulative Neurotechnology-Based Therapy for Upper-Limb Rehabilitation in Severely Impaired Chronic Stroke Patients: The AVANCER Study Protocol.

Effective, patient-tailored rehabilitation to restore upper-limb motor function in severely impaired stroke patients is still missing. If suitably combined and administered in a personalized fashion, neurotechnologies offer a large potential to assist rehabilitative therapies to enhance individual treatment effects. AVANCER (clinicaltrials.gov NCT04448483) is a two-center proof-of-concept trial with an individual based cumulative longitudinal intervention design aiming at reducing upper-limb motor impairment in severely affected stroke patients with the help of multiple neurotechnologies. AVANCER will determine feasibility, safety, and effectivity of this innovative intervention. Thirty chronic stroke patients with a Fugl-Meyer assessment of the upper limb (FM-UE) <20 will be recruited at two centers. All patients will undergo the cumulative personalized intervention within two phases: the first uses an EEG-based brain-computer interface to trigger a variety of patient-tailored movements supported by multi-channel functional electrical stimulation in combination with a hand exoskeleton. This phase will be continued until patients do not improve anymore according to a quantitative threshold based on the FM-UE. The second interventional phase will add non-invasive brain stimulation by means of anodal transcranial direct current stimulation to the motor cortex to the initial approach. Each phase will last for a minimum of 11 sessions. Clinical and multimodal assessments are longitudinally acquired, before the first interventional phase, at the switch to the second interventional phase and at the end of the second interventional phase. The primary outcome measure is the 66-point FM-UE, a significant improvement of at least four points is hypothesized and considered clinically relevant. Several clinical and system neuroscience secondary outcome measures are additionally evaluated. AVANCER aims to provide evidence for a safe, effective, personalized, adjuvant treatment for patients with severe upper-extremity impairment for whom to date there is no efficient treatment available.

Spelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training.

Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state. Here, we implanted two 64 microelectrode arrays in the supplementary and primary motor cortex of a patient in a completely locked-in state with ALS. The patient modulated neural firing rates based on auditory feedback and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides evidence that brain-based volitional communication is possible even in a completely locked-in state.

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.

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.

Brain Computer Interfaces for Assisted Communication in Paralysis and Quality of Life.

The rapid evolution of Brain-Computer Interface (BCI) technology and the exponential growth of BCI literature during the past 20 years is a consequence of increasing computational power and the achievements of statistical learning theory and machine learning since the 1960s. Despite this rapid scientific progress, the range of successful clinical and societal applications remained limited, with some notable exceptions in the rehabilitation of chronic stroke and first steps towards BCI-based assisted verbal communication in paralysis. In this contribution, we focus on the effects of noninvasive and invasive BCI-based verbal communication on the quality of life (QoL) of patients with amyotrophic lateral sclerosis (ALS) in the locked-in state (LIS) and the completely locked-in state (CLIS). Despite a substantial lack of replicated scientific data, this paper complements the existing methodological knowledge and focuses future investigators' attention on (1) Social determinants of QoL and (2) Brain reorganization and behavior. While it is not documented in controlled studies that the good QoL in these patients is a consequence of BCI-based neurorehabilitation, the proposed determinants of QoL might become the theoretical background needed to develop clinically more useful BCI systems and to evaluate the effects of BCI-based communication on QoL for advanced ALS patients and other forms of severe paralysis.

Binary Semantic Classification Using Cortical Activation with Pavlovian-Conditioned Vestibular Responses in Healthy and Locked-In Individuals.

To develop a more reliable brain-computer interface (BCI) for patients in the completely locked-in state (CLIS), here we propose a Pavlovian conditioning paradigm using galvanic vestibular stimulation (GVS), which can induce a strong sensation of equilibrium distortion in individuals. We hypothesized that associating two different sensations caused by two-directional GVS with the thoughts of "yes" and "no" by individuals would enable us to emphasize the differences in brain activity associated with the thoughts of yes and no and hence help us better distinguish the two from electroencephalography (EEG). We tested this hypothesis with 11 healthy and 1 CLIS participant. Our results showed that, first, conditioning of GVS with the thoughts of yes and no is possible. And second, the classification of whether an individual is thinking "yes" or "no" is significantly improved after the conditioning, even in the absence of subsequent GVS stimulations. We observed average classification accuracy of 73.0% over 11 healthy individuals and 85.3% with the CLIS patient. These results suggest the establishment of GVS-based Pavlovian conditioning and its usability as a noninvasive BCI.

EEG power spectral density in locked-in and completely locked-in state patients: a longitudinal study.

Persons with their eye closed and without any means of communication is said to be in a completely locked-in state (CLIS) while when they could still open their eyes actively or passively and have some means of communication are said to be in locked-in state (LIS). Two patients in CLIS without any means of communication, and one patient in the transition from LIS to CLIS with means of communication, who have Amyotrophic Lateral Sclerosis were followed at a regular interval for more than 1 year. During each visit, resting-state EEG was recorded before the brain-computer interface (BCI) based communication sessions. The resting-state EEG of the patients was analyzed to elucidate the evolution of their EEG spectrum over time with the disease's progression to provide future BCI-research with the relevant information to classify changes in EEG evolution. Comparison of power spectral density (PSD) of these patients revealed a significant difference in the PSD's of patients in CLIS without any means of communication and the patient in the transition from LIS to CLIS with means of communication. The EEG of patients without any means of communication is devoid of alpha, beta, and higher frequencies than the patient in transition who still had means of communication. The results show that the change in the EEG frequency spectrum may serve as an indicator of the communication ability of such patients.

Neurophysiological aspects of the completely locked-in syndrome in patients with advanced amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) patients in completely locked-in syndrome (CLIS) are incapable of expressing themselves, and their state of consciousness and awareness is difficult to evaluate. Due to the complete paralysis included paralysis of eye muscles, any assessment of the perceptual and psychophysiological state can only be implemented in passive experimental paradigms with neurophysiological recordings. METHODS: Four patients in CLIS were investigated in several experiments including resting state, visual stimulation (eyes open vs eyes closed), auditory stimulation (modified local-global paradigm), somatosensory stimulation (electrical stimulation of the median nerve), and during sleep. RESULTS: All patients showed altered neurophysiological metrics, but a unique and common pattern could not be found between patients. However, slowing of the electroencephalography (EEG) and attenuation or absence of alpha wave activity was common in all patients. In two of the four patients, a slow dominant frequency emerged at 4 Hz with synchronized EEG at all channels. In the other two patients slowing of EEG appears less synchronized. EEGs between eyes open and eyes closed were significantly different in all patients. The dominant slow frequency during the day changes during slow-wave sleep (supposedly sleep stage 3) to even slower frequencies below 2 Hz. Somatosensory evoked potentials (SEPs) were absent or significantly altered in comparison to healthy subjects, similarly for auditory evoked potentials (AEPs). CONCLUSIONS: The heterogeneity of the results underscores the fact that no single neurophysiological index is available to assess psychophysiological states in unresponsive ALS patients in CLIS. This caveat may also be valid for the assessment of cognitive processes; a functioning BCI can be the solution. SIGNIFICANCE: Most of the studies of the neurophysiology of ALS patients focused on the early stage of the disease, and there are very few studies on the late stage when patients are completely paralyzed with no means of communication (i.e., CLIS). This study provides quantitative metrics of different neurophysiological aspects of these patients.

Functional synergy recruitment index as a reliable biomarker of motor function and recovery in chronic stroke patients.

Objective. Stroke affects the expression of muscle synergies underlying motor control, most notably in patients with poorer motor function. The majority of studies on muscle synergies have conventionally approached this analysis by assuming alterations in the inner structures of synergies after stroke. Although different synergy-based features based on this assumption have to some extent described pathological mechanisms in post-stroke neuromuscular control, a biomarker that reliably reflects motor function and recovery is still missing.Approach. Based on the theory of muscle synergies, we alternatively hypothesize that functional synergy structures are physically preserved and measure the temporal correlation between the recruitment profiles of healthy modules by paretic and healthy muscles, a feature hereafter reported as the FSRI. We measured clinical scores and extracted the muscle synergies of both ULs of 18 chronic stroke survivors from the electromyographic activity of 8 muscles during bilateral movements before and after 4 weeks of non-invasive BMI controlled robot therapy and physiotherapy. We computed the FSRI as well as features quantifying inter-limb structural differences and evaluated the correlation of these synergy-based measures with clinical scores.Main results. Correlation analysis revealed weak relationships between conventional features describing inter-limb synergy structural differences and motor function. In contrast, FSRI values during specific or combined movement data significantly correlated with UL motor function and recovery scores. Additionally, we observed that BMI-based training with contingent positive proprioceptive feedback led to improved FSRI values during the specific trained finger extension movement.Significance. We demonstrated that FSRI can be used as a reliable physiological biomarker of motor function and recovery in stroke, which can be targeted via BMI-based proprioceptive therapies and adjuvant physiotherapy to boost effective rehabilitation.

Balancing the brain of offenders with psychopathy? Resting state EEG and electrodermal activity after a pilot study of brain self-regulation training.

Although investigation of the brains of criminals began quite early in the history of psychophysiological research, little is known about brain plasticity of offenders with psychopathy. Building on our preliminary study reporting successful brain self-regulation using slow cortical potential (SCP) neurofeedback in offenders with psychopathy, we investigated the central nervous and autonomic peripheral changes occurring after brain self-regulation in a group of severe male offenders with psychopathy. Regarding the central nervous system, an overall suppression of the psychopathic overrepresentation of slow frequency bands was found, such as delta and theta band activity, after EEG neurofeedback. In addition, an increase in alpha band activity could be observed after the SCP self-regulation training. Electrodermal activity adaptively changed according to the regulation task, and this flexibility improved over training time. The results of this study point towards a constructive learning process and plasticity in neural and peripheral measures of offenders with psychopathy.

A dataset of EEG and EOG from an auditory EOG-based communication system for patients in locked-in state.

The dataset presented here contains recordings of electroencephalogram (EEG) and electrooculogram (EOG) from four advanced locked-in state (LIS) patients suffering from ALS (amyotrophic lateral sclerosis). These patients could no longer use commercial eye-trackers, but they could still move their eyes and used the remnant oculomotor activity to select letters to form words and sentences using a novel auditory communication system. Data were recorded from four patients during a variable range of visits (from 2 to 10), each visit comprised of 3.22 ± 1.21 days and consisted of 5.57 ± 2.61 sessions recorded per day. The patients performed a succession of different sessions, namely, Training, Feedback, Copy spelling, and Free spelling. The dataset provides an insight into the progression of ALS and presents a valuable opportunity to design and improve assistive and alternative communication technologies and brain-computer interfaces. It might also help redefine the course of progression in ALS, thereby improving clinical judgement and treatment.

Electroencephalography of completely locked-in state patients with amyotrophic lateral sclerosis.

Patients in completely locked-in state (CLIS) due to amyotrophic lateral sclerosis (ALS) lose the control of each and every muscle of their body rendering them motionless and without any means of communication. Though some studies have attempted to develop brain-computer interface (BCI)-based communication methods with CLIS patients, little information is available of the neuroelectric brain activity of CLIS patients. However, because of the difficulties with and often loss of communication, the neuroelectric signature may provide some indications of the state of consciousness in these patients. We recorded electroencephalography (EEG) signals from 10 CLIS patients during resting state and compared their power spectral densities with those of healthy participants in fronto-central, central, and centro-parietal channels. The results showed significant power reduction in the high alpha, beta, and gamma bands in CLIS patients, indicating the dominance of slower EEG frequencies in their oscillatory activity. This is the first study showing group-level EEG change of CLIS patients, though the reason for the observed EEG change cannot be concluded without any reliable communication methods with this population.