Neurofeedback and epilepsy: Renaissance of an old self-regulation method?

Neurofeedback is a brain-computer interface tool enabling the user to self-regulate their neuronal activity, and ultimately, induce long-term brain plasticity, making it an interesting instrument to cure brain disorders. Although this method has been used successfully in the past as an adjunctive therapy in drug-resistant epilepsy, this approach remains under-explored and deserves more rigorous scientific inquiry. In this review, we present early neurofeedback protocols employed in epilepsy and provide a critical overview of the main clinical studies. We also describe the potential neurophysiological mechanisms through which neurofeedback may produce its therapeutic effects. Finally, we discuss how to innovate and standardize future neurofeedback clinical trials in epilepsy based on evidence from recent research studies.

Secondary somatosensory area is involved in vibrotactile temporal-structure processing: MEG analysis of slow cortical potential shifts in humans.

Purpose: Temporal-structure discrimination is an essential dimension of tactile processing. Exploring object surface by touch generates vibrotactile input with various temporal dynamics, which gives diversity to tactile percepts. Here, we examined whether slow cortical potential shifts (SCPs) (<1 Hz) evoked by long vibrotactile stimuli can reflect active temporal-structure processing.Materials and methods: Vibrotactile-evoked magnetic brain responses were recorded in 10 right-handed healthy volunteers using a piezoelectric-based stimulator and whole-head magnetoencephalography. A series of vibrotactile train stimuli with various temporal structures were delivered to the right index finger. While all trains consisted of identical number (15) of stimuli delivered within a fixed duration (1500 ms), temporal structures were varied by modulating inter-stimulus intervals (ISIs). Participants judged regularity/irregularity of ISI for each train in the active condition, whereas they ignored the stimuli while performing a visual distraction task in the passive condition. We analysed the spatiotemporal features of SCPs and their behaviour using the minimum norm estimates with the dynamic statistical parametric mapping.Results: SCPs were localized to contralateral primary somatosensory area (S1), contralateral superior temporal gyrus, and contralateral as well as ipsilateral secondary somatosensory areas (S2). A significant enhancement of SCPs was observed in the ipsilateral S2 (S2i) in the active condition, whereas such effects were absent in the other regions. We also found a significant larger amplitude difference between the regular- and irregular-stimulus evoked S2i responses during the active condition than during the passive condition.Conclusions: This study suggests that S2 subserves the temporal dimension of vibrotactile processing.

Juxtaposing the real-time unfolding of subjective experience and ERP neuromarker dynamics.

Electroencephalographic (EEG) potentials have remained a valuable source of data and theories concerning neural correlates of consciousness (NCC). The EEG based methods are far from being exhausted and are continually valuable in the quest for the markers of NCC. To set the background for the research presented in this issue, we review the published work on EEG-based markers of NCC. The article is organized according to the principle of the time-course aspect of brain potentials with regard to the stimuli for which subject's awareness is experimentally measured and/or manipulated. We treat brain potentials as the principal dependent measure as well as independent variable. More specifically, we also draw attention to the fact that in the overwhelming share of studies relative negativization of the ERPs tends to mark NCC.

Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement.

Slow Cortical Potential Neurofeedback in Chronic Tinnitus Therapy: A Case Report.

This study is the first to demonstrate outcomes of slow cortical potential (SCP) Neurofeedback training in chronic tinnitus. A 50-year old male patient with tinnitus participated in three SCP training blocks, separated with 1-month breaks. After the training the patient reported decreased tinnitus loudness and pitch, as well as improved quality of daily life. A quantitative electroencephalography analysis revealed close to normal changes of resting state bioelectrical activity in cortical areas considered to be involved in tinnitus generation. The present case study indicates that SCP Neurofeedback training can be considered a promising method for tinnitus treatment.

Spatiotemporal dissociation of brain activity underlying subjective awareness, objective performance and confidence.

Despite intense recent research, the neural correlates of conscious visual perception remain elusive. The most established paradigm for studying brain mechanisms underlying conscious perception is to keep the physical sensory inputs constant and identify brain activities that correlate with the changing content of conscious awareness. However, such a contrast based on conscious content alone would not only reveal brain activities directly contributing to conscious perception, but also include brain activities that precede or follow it. To address this issue, we devised a paradigm whereby we collected, trial-by-trial, measures of objective performance, subjective awareness, and the confidence level of subjective awareness. Using magnetoencephalography recordings in healthy human volunteers, we dissociated brain activities underlying these different cognitive phenomena. Our results provide strong evidence that widely distributed slow cortical potentials (SCPs) correlate with subjective awareness, even after the effects of objective performance and confidence were both removed. The SCP correlate of conscious perception manifests strongly in its waveform, phase, and power. In contrast, objective performance and confidence were both contributed by relatively transient brain activity. These results shed new light on the brain mechanisms of conscious, unconscious, and metacognitive processing.

Coherent slow cortical potentials reveal a superior localization of resting-state functional connectivity using voltage-sensitive dye imaging.

The resting-state functional connectivity (RSFC) of spontaneous hemodynamic fluctuations is widely used to investigate large-scale functional brain networks based on neurovascular mechanisms. However, high-resolution RSFC networks based on neural activity have not been disclosed to explore the neural basis of these spontaneous hemodynamic signals. The present study examines the neural RSFC networks in mice at high spatial resolution using optical imaging with voltage-sensitive dyes (VSDs). Our results show that neural RSFC networks for the slow cortical potentials (0.1-4Hz) showed similar correlation patterns to the RSFC networks for the spontaneous hemodynamic signals, indicating a tight coupling between the slow cortical potential and the spontaneous hemodynamic signals during rest, but the bilateral symmetry of the RSFC networks for the slow cortical potentials was significantly lower than that for the spontaneous hemodynamic signals. Moreover, similar asymmetric neural activation patterns could also be found between the bilateral cortexes after stimulating the paws of mice. By increasing anesthetic levels to induce the reduction of consciousness, the RSFC networks for the slow cortical potentials persisted, but those for the spontaneous hemodynamic signals became discrete. These results suggest that the coherent slow cortical potentials underlie the spontaneous hemodynamic fluctuations and reveal a superior localization of RSFC networks. VSD imaging may potentially be used to examine the RSFC of neural activity, particularly under conditions of impaired neurovascular coupling.

First-person approaches in neuroscience of consciousness: brain dynamics correlate with the intention to act.

The belief in free will has been frequently challenged since Benjamin Libet published his famous experiment in 1983. Although Libet's experiment is highly dependent upon subjective reports, no study has been conducted that focused on a first-person or introspective perspective of the task. We took a neurophenomenological approach in an N=1 study providing reliable and valid measures of the first-person perspective in conjunction with brain dynamics. We found that a larger readiness potential (RP) is attributable to more frequent occurrences of self-initiated movements during negative deflections of the slow cortical potentials (SCP). These negative deflections occur in parallel with an inner impulse reported by an expert meditator which may in turn lead to a voluntary act. We demonstrate in this proof-of-principle approach that the first-person perspective obtained by an expert meditator in conjunction with neural signal analysis can contribute to our understanding of the neural underpinnings of voluntary acts.

Frequency-specific neural signatures of perceptual content and perceptual stability.

In the natural environment, we often form stable perceptual experiences from ambiguous and fleeting sensory inputs. Which neural activity underlies the content of perception and which neural activity supports perceptual stability remains an open question. We used a bistable perception paradigm involving ambiguous images to behaviorally dissociate perceptual content from perceptual stability, and magnetoencephalography to measure whole-brain neural dynamics in humans. Combining multivariate decoding and neural state-space analyses, we found frequency-band-specific neural signatures that underlie the content of perception and promote perceptual stability, respectively. Across different types of images, non-oscillatory neural activity in the slow cortical potential (<5 Hz) range supported the content of perception. Perceptual stability was additionally influenced by the amplitude of alpha and beta oscillations. In addition, neural activity underlying perceptual memory, which supports perceptual stability when sensory input is temporally removed from view, also encodes elapsed time. Together, these results reveal distinct neural mechanisms that support the content versus stability of visual perception.

Volitional modification of brain activity in adolescents with Autism Spectrum Disorder: A Bayesian analysis of Slow Cortical Potential neurofeedback.

Autism spectrum disorder is (ASD) characterized by a persisting triad of impairments of social interaction, language as well as inflexible, stereotyped and ritualistic behaviors. Increasingly, scientific evidence suggests a neurobiological basis of these emotional, social and cognitive deficits in individuals with ASD. The aim of this randomized controlled brain self-regulation intervention study was to investigate whether the core symptomatology of ASD could be reduced via an electroencephalography (EEG) based brain self-regulation training of Slow Cortical Potentials (SCP). 41 male adolescents with ASD were recruited and allocated to a) an experimental group undergoing 24 sessions of EEG-based brain training (n1 = 21), or to b) an active control group undergoing conventional treatment (n2 = 20), that is, clinical counseling during a 3-months intervention period. We employed real-time neurofeedback training recorded from a fronto-central electrode intended to enable participants to volitionally regulate their brain activity. Core autistic symptomatology was measured at six time points during the intervention and analyzed with Bayesian multilevel approach to characterize changes in core symptomatology. Additional Bayesian models were formulated to describe the neural dynamics of the training process as indexed by SCP (time-domain) and power density (PSD, frequency-domain) measures. The analysis revealed a substantial improvement in the core symptomatology of ASD in the experimental group (reduction of 21.38 points on the Social Responsiveness Scale, SD = 5.29), which was slightly superior to that observed in the control group (evidence Ratio = 5.79). Changes in SCP manifested themselves as different trajectories depending on the different feedback conditions and tasks. Further, the model of PSD revealed a continuous decrease in delta power, parallel to an increase in alpha power. Most notably, a non-linear (quadratic) model turned out to be better at predicting the data than a linear model across all analyses. Taken together, our analyses suggest that behavioral and neural processes of change related to neurofeedback training are complex and non-linear. Moreover, they have implications for the design of future trials and training protocols.

Differences in Intersubject Early Readiness Potentials Between Voluntary and Instructed Actions.

Readiness potential (RP) is a slow negative electroencephalogram (EEG) potential prior to voluntary action and was first described by Kornhuber and Deecke (1965). Recent studies have demonstrated that a few subjects do not exhibit standard RP before voluntary action. In our previous study, we also found that some subjects did not show an early RP preceding instructed action. Although this phenomenon may be meaningful, no studies have yet investigated its origins. In the present study, we designed and implemented an experimental paradigm involving voluntary and instructed actions in the form of hand movements from 29 subjects with concurrent acquisition of EEGs. According to whether the subjects showed a standard RP waveform during instructed action, they were divided into the SHOW and NOSHOW group. Then, the RPs and voltage topographies were plotted for each group. Finally, the slope of each epoch at the early RP phase was estimated. We showed that early RPs were absent in 14 of 29 subjects during instructed actions. Besides, based on the slow cortical potential (SCP) sampling hypothesis, we also showed a decreased proportion in the negative potential for the NOSHOW group. Our results suggested that early RP is absent among approximately half of subjects during instructed action and that the decreased proportion of negative potential shifts may account for the absence of early RP in the NOSHOW group.

Do scalp-recorded slow potentials during neuro-feedback training reflect the cortical activity?

OBJECTIVE: Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs) <0.5 Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis. METHODS: The scalp and subdural SPs were simultaneously recorded during NFB training by the DC-EEG machine while undergoing invasive recordings before epilepsy surgery in 10 patients with refractory partial epilepsy. The SPs at the vertex electrode were used as a reference for coherence analysis. RESULTS: The coherence of SPs negatively correlated with the distance between the subdural and scalp electrodes. A significant negative correlation was noted between the linear subdural-scalp electrode distance and the coherence value (r =  - 0.916, p < 0.001). CONCLUSION: Scalp-recorded SPs from the vertex area primarily reflect the cortical activity of high lateral convexity. SIGNIFICANCE: Our results strongly suggest that SPs in NFB recorded from the vertex scalp electrode is derived from the cortices of high lateral convexity but not from the artifacts, such as GSR.

Exploring the maximum duration of the contingent negative variation.

While the contingent negative variation (CNV) has been the subject of extensive research over the last fifty years, the maximum duration during which such cortical negativity can be maintained has, to the best of our knowledge, never been systematically explored. Participants were presented with the classic S1-S2 paradigm task, where a warning stimulus (S1) acts as a cue for the appearance of an imperative stimulus (S2). A fast motor response was required upon S2 arrival. Inter-stimulus intervals (ISIs) of 2.5, 5, 7.5 and 10 s duration were presented in blocked fashion. Data was analysed using both EEG referenced to linked mastoids and the current source density (CSD) technique, which maximizes the cortical origin of the measured voltage. Mean late CNV (lCNV) amplitude was found to be significantly higher for fast reaction time (RT) trials when CSD data was split according to the median into 'fast' and 'slow' RT halves. Post-hoc comparisons showed that this RT effect was particularly strong for the 10 s condition. This may be explained by the lack of an lCNV component and thus of cortical negativity prior to S2 in the 10 s condition. Our results suggest that intervals of a duration between 7.5 and 10 s represent the upper boundary during which the lCNV component can be elicited.

'Catching the waves' - slow cortical potentials as moderator of voluntary action.

The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

Slow cortical potential neurofeedback and self-management training in outpatient care for children with ADHD: study protocol and first preliminary results of a randomized controlled trial.

BACKGROUND: Treatment for children with attention deficit/hyperactivity disorder (ADHD) today is predominantly pharmacological. While it is the most common treatment, it might not always be the most appropriate one. Moreover, long term effects remain unclear. Behavior therapy (BT) and non-pharmacological treatments such as neurofeedback (NF) are promising alternatives, though there are no routine outpatient care/effectiveness studies yet that have included children with medication or changes in medication. METHODS/DESIGN: This paper presents the protocol of a randomized controlled trial to compare the effectiveness of a Slow Cortical Potential (SCP) NF protocol with self-management (SM) in a high frequent outpatient care setting. Both groups (NF/SM) receive a total of 30 high frequent therapy sessions. Additionally, 6 sessions are reserved for comorbid problems. The primary outcome measure is the reduction of ADHD core symptoms according to parent and teacher ratings. PRELIMINARY RESULTS: Untill now 58 children were included in the study (48 males), with a mean age of 8.42 (1.34) years, and a mean IQ of 110 (13.37). Conners-3 parent and teacher ratings were used to estimate core symptom change. Since the study is still ongoing, and children are in different study stages, pre-post and follow-up results are not yet available for all children included. Preliminary results suggest overall good pre-post effects, though. For parent and teacher ratings an ANOVA with repeated measures yielded overall satisfying pre-post effects (η (2) 0.175-0.513). Differences between groups (NF vs. SM) could not yet be established (p = 0.81). DISCUSSION: This is the first randomized controlled trial to test the effectiveness of a NF protocol in a high frequent outpatient care setting that does not exclude children on or with changes in medication. First preliminary results show positive effects. The rationale for the trial, the design, and the strengths and limitations of the study are discussed. TRIAL REGISTRATION: This trial is registered in www.clinicaltrials.gov as NCT01879644.

The readiness potential reflects intentional binding.

When a voluntary action is causally linked with a sensory outcome, the action and its consequent effect are perceived as being closer together in time. This effect is called intentional binding. Although many experiments were conducted on this phenomenon, the underlying neural mechanisms are not well understood. While intentional binding is specific to voluntary action, we presumed that preconscious brain activity (the readiness potential, RP), which occurs before an action is made, might play an important role in this binding effect. In this study, the brain dynamics were recorded with electroencephalography (EEG) and analyzed in single-trials in order to estimate whether intentional binding is correlated with the early neural processes. Moreover, we were interested in different behavioral performance between meditators and non-meditators since meditators are expected to be able to keep attention more consistently on a task. Thus, we performed the intentional binding paradigm with 20 mindfulness meditators and compared them to matched controls. Although, we did not observe a group effect on either behavioral data or EEG recordings, we found that self-initiated movements following ongoing negative deflections of slow cortical potentials (SCPs) result in a stronger binding effect compared to positive potentials, especially regarding the perceived time of the consequent effect. Our results provide the first direct evidence that the early neural activity within the range of SCPs affects perceived time of a sensory outcome that is caused by intentional action.

Slow cortical potential and theta/beta neurofeedback training in adults: effects on attentional processes and motor system excitability.

Neurofeedback (NF) is being successfully applied, among others, in children with attention deficit/hyperactivity disorder (ADHD) and as a peak performance training in healthy subjects. However, the neuronal mechanisms mediating a successful NF training have not yet been sufficiently uncovered for both theta/beta (T/B), and slow cortical potential (SCP) training, two protocols established in NF in ADHD. In the present, randomized, controlled investigation in adults without a clinical diagnosis (n = 59), the specificity of the effects of these two NF protocols on attentional processes and motor system excitability were to be examined, focusing on the underlying neuronal mechanisms. Neurofeedback training consisted of 10 double sessions, and self-regulation skills were analyzed. Pre- and post-training assessments encompassed performance and event-related potential measures during an attention task, and motor system excitability assessed by transcranial magnetic stimulation. Some NF protocol-specific effects have been obtained. However, due to the limited sample size medium effects did not reach the level of significance. Self-regulation abilities during negativity trials of the SCP training were associated with increased contingent negative variation amplitudes, indicating improved resource allocation during cognitive preparation. Theta/beta training was associated with increased response speed and decreased target-P3 amplitudes after successful theta/beta regulation suggested reduced attentional resources necessary for stimulus evaluation. Motor system excitability effects after theta/beta training paralleled the effects of methylphenidate. Overall, our results are limited by the non-sufficiently acquired self-regulation skills, but some specific effects between good and poor learners could be described. Future studies with larger sample sizes and sufficient acquisition of self-regulation skills are needed to further evaluate the protocol-specific effects on attention and motor system excitability reported.