A randomized-controlled neurofeedback trial in adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset disorder persisting into adulthood for a large proportion of cases. Neurofeedback (NF) has shown promising results in children with ADHD, but randomized controlled trials in adults with ADHD are scarce. We aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. Patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at 6-months follow-up (FU) including 3 booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. We conclude that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. We did not find any significant differences in outcome between groups when looking at the whole sample. When evaluating learners only, they demonstrate superior effects as compared to non-learners, which suggests specific effects in addition to non-specific effects of NF when learning occurs.

Can neurophysiological markers of anticipation and attention predict ADHD severity and neurofeedback outcomes?

Neurophysiological measures of preparation and attention are often atypical in ADHD. Still, replicated findings that these measures predict which patients improve after Neurofeedback (NF), reveal neurophysiological specificity, and reflect ADHD-severity are limited. METHODS: We analyzed children's preparatory (CNV) and attentional (Cue-P3) brain activity and behavioral performance during a cued Continuous Performance Task (CPT) before and after slow cortical potential (SCP)-NF or semi-active control treatment (electromyogram biofeedback). Mixed-effects models were performed with 103 participants at baseline and 77 were assessed for pre-post comparisons focusing on clinical outcome prediction, specific neurophysiological effects of NF, and associations with ADHD-severity. RESULTS: Attentional and preparatory brain activity and performance were non-specifically reduced after treatment. Preparatory activity in the SCP-NF group increased with clinical improvement. Several performance and brain activity measures predicted non-specific treatment outcome. CONCLUSION: Specific neurophysiological effects after SCP-NF were limited to increased neural preparation associated with improvement on ADHD-subscales, but several performance and neurophysiological measures of attention predicted treatment outcome and reflected symptom severity in ADHD. The results may help to optimize treatment.

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.

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.

Sustained effects of neurofeedback in ADHD: a systematic review and meta-analysis.

Neurofeedback (NF) has gained increasing interest in the treatment of attention-deficit/hyperactivity disorder (ADHD). Given learning principles underlie NF, lasting clinical treatment effects may be expected. This systematic review and meta-analysis addresses the sustainability of neurofeedback and control treatment effects by considering randomized controlled studies that conducted follow-up (FU; 2-12 months) assessments among children with ADHD. PubMed and Scopus databases were searched through November 2017. Within-group and between-group standardized mean differences (SMD) of parent behavior ratings were calculated and analyzed. Ten studies met inclusion criteria (NF: ten studies, N = 256; control: nine studies, N = 250). Within-group NF effects on inattention were of medium effect size (ES) (SMD = 0.64) at post-treatment and increased to a large ES (SMD = 0.80) at FU. Regarding hyperactivity/impulsivity, NF ES were medium at post-treatment (SMD = 0.50) and FU (SMD = 0.61). Non-active control conditions yielded a small significant ES on inattention at post-treatment (SMD = 0.28) but no significant ES at FU. Active treatments (mainly methylphenidate), had large ES for inattention (post: SMD = 1.08; FU: SMD = 1.06) and medium ES for hyperactivity/impulsivity (post: SMD = 0.74; FU: SMD = 0.67). Between-group analyses also revealed an advantage of NF over non-active controls [inattention (post: SMD = 0.38; FU: SMD = 0.57); hyperactivity-impulsivity (post: SMD = 0.25; FU: SMD = 0.39)], and favored active controls for inattention only at pre-post (SMD = - 0.44). Compared to non-active control treatments, NF appears to have more durable treatment effects, for at least 6 months following treatment. More studies are needed for a properly powered comparison of follow-up effects between NF and active treatments and to further control for non-specific effects.

Identification of neurophysiological biotypes in attention deficit hyperactivity disorder.

AIM: Findings on neurophysiological alterations in attention deficit hyperactivity disorder (ADHD) have been proposed to underlie ADHD symptoms, with different etiological pathways for different patient biotypes. We aimed at determining whether neurophysiological deviations confirm distinct neurophysiological profiles in ADHD, thus providing direct evidence for the endophenotype concept. METHODS: Neurophysiological biotypes were investigated in 87 adult patients with ADHD using cluster analysis. Parameters fed into the analysis comprised both hemodynamic and electrophysiological data. To validate results, the independent variables of the clusters were compared with healthy controls. RESULTS: Cluster analysis yielded three neurophysiologically based ADHD biotypes showing: (i) above-average functioning in attention allocation; (ii) difficulties in attention allocation and inhibitory control but elevated frontal activation during a working memory task; and (iii) functional impairments in state regulation. CONCLUSION: Classifying patients with ADHD into neurophysiological biotypes sheds light on etiological pathways, with implications for diagnostics and (individualized) treatment options.

EMG biofeedback training in adult attention-deficit/hyperactivity disorder: An active (control) training?

OBJECTIVE: The present study aimed at revealing neurophysiological effects induced by electromyography (EMG) based biofeedback, considered as a semi-active control condition in neurofeedback studies, in adult attention-deficit/hyperactivity disorder (ADHD) patients. METHODS: 20 adult ADHD patients trained their muscle activity in the left and right supraspinatus muscle over the course of 30 EMG biofeedback sessions. Changes induced by the EMG feedback were evaluated at a clinical and neurophysiological level; additionally, the relation between changes in EEG activity recorded at the vertex over the training course and changes of symptom severity over the treatment course were assessed in order to investigate the mechanisms underlying clinical effects of EMG biofeedback. RESULTS: Participants showed significant behavioral improvements on a self-rating scale. There was a significant increase in alpha power, but no significant changes in the delta frequency range; changes in the theta and beta frequency range were not significant after adjustment for multiple comparisons. No statistically significant correlation was found between changes in EEG frequency bands and changes in ADHD symptoms. CONCLUSIONS: The current results assessed by means of a single-electrode EEG constitute a starting point regarding a clearer understanding of mechanisms underlying clinical effects of EMG biofeedback. Although we did not reveal systematic effects induced by EMG feedback on brain activity it remains an open question whether EMG biofeedback induces changes in brain regions or parameters we did not gather in the present study (e.g. motor cortex).

Neurofeedback of Slow Cortical Potentials in Children with Attention-Deficit/Hyperactivity Disorder: A Multicenter Randomized Trial Controlling for Unspecific Effects.

Background: Neurofeedback (NF) in children with attention-deficit/hyperactivity disorder (ADHD) has been investigated in a series of studies over the last years. Previous studies did not unanimously support NF as a treatment in ADHD. Most studies did not control for unspecific treatment effects and did not demonstrate that self-regulation took place. The present study examined the efficacy of NF in comparison to electromyographic (EMG) feedback to control for unspecific effects of the treatment, and assessed self-regulation of slow cortical potentials (SCPs). Methods: A total of 150 children aged 7-9 years diagnosed with ADHD (82% male; 43% medicated) were randomized to 25 sessions of feedback of SCPs (NF) or feedback of coordination of the supraspinatus muscles (EMG). The primary endpoint was the change in parents' ratings of ADHD core symptoms 4 weeks after the end of treatment compared to pre-tests. Results: Children in both groups showed reduced ADHD-core symptoms (NF 0.3, 95% CI -0.42 to -0.18; EMG 0.13, 95% CI -0.26 to -0.01). NF showed a significant superiority over EMG (treatment difference 0.17, 95% CI 0.02-0.3, p = 0.02). This yielded an effect size (ES) of d = 0.57 without and 0.40 with baseline observation carried forward (BOCF). The sensitivity analysis confirmed the primary result. Successful self-regulation of brain activity was observed only in NF. As a secondary result teachers reported no superior improvement from NF compared to EMG, but within-group analysis revealed effects of NF on the global ADHD score, inattention, and impulsivity. In contrast, EMG feedback did not result in changes despite more pronounced self-regulation learning. Conclusions: Based on the primary parent-rated outcome NF proved to be superior to a semi-active EMG feedback treatment. The study supports the feasibility and efficacy of NF in a large sample of children with ADHD, based on both specific and unspecific effects. Trial Register: Current controlled trials ISRCTN76187185, registered 5 February 2009.

Near-Infrared Spectroscopy based Neurofeedback of Prefrontal Cortex Activity: A Proof-of-Concept Study.

Neurofeedback is a promising tool for treatment and rehabilitation of several patient groups. In this proof of principle study, near-infrared spectroscopy (NIRS) based neurofeedback of frontal cortical areas was investigated in healthy adults. Main aims were the assessment of learning, the effects on performance in a working memory (n-back) task and the impact of applied strategies on regulation. 13 healthy participants underwent eight sessions of NIRS based neurofeedback within 2 weeks to learn to voluntarily up-regulate hemodynamic activity in prefrontal areas. An n-back task in pre-/post measurements was used to monitor neurocognitive changes. Mean oxygenated hemoglobin (O2Hb) amplitudes over the course of the sessions as well as during the n-back task were evaluated. 12 out of 13 participants were able to regulate their frontal hemodynamic response via NIRS neurofeedback. However, no systematic learning effects were observed in frontal O2Hb amplitudes over the training course in our healthy sample. We found an impact of applied strategies in only 5 out of 13 subjects. Regarding the n-back task, neurofeedback appeared to induce more focused and specific brain activation compared to pre-training measurement. NIRS based neurofeedback is a feasible and potentially effective method, with an impact on activation patterns in a working memory task. Ceiling effects might explain the lack of a systematic learning pattern in healthy subjects. Clinical studies are needed to show effects in patients exhibiting pathological deviations in prefrontal function.

Underarousal in Adult ADHD: How Are Peripheral and Cortical Arousal Related?

In children and adults with attention deficit/hyperactivity disorder (ADHD), a general slowing of spontaneous electroencephalographic (EEG) brain activity and a decrease of event-related potential amplitudes such as the contingent negative variation (CNV) are observed. Additionally, some studies have reported decreased skin conductance level (SCL) in this clinical population leading to the hypothesis of a peripheral hypoarousal, which may be a target of biofeedback treatment in addition to or instead of neurofeedback. To our knowledge, the relationship between SCL and CNV has not been simultaneously investigated in one experiment. Using the theoretical background of the hypoarousal model, this article aims to gain more insight into the differences and correlations of cortical (CNV) and peripheral (SCL) arousal in adults with ADHD. A sample of 23 adults with ADHD and 22 healthy controls underwent an auditory Go-NoGo task with simultaneous 22-channel EEG and SCL recordings. Reaction time (RT) and reaction time variability (RTV) were also measured to assess task performance. Significantly decreased CNV amplitude and significantly higher RTV were observed in the ADHD group, reflecting cortical underarousal and problems with sustained attention. No significant correlation between peripheral underarousal and cortical underarousal was observed in the ADHD group or the control group. The observed cortical underarousal reflected in the decreased CNV supports the notion of a reduced CNV amplitude as a possible biomarker for ADHD. However, the connection between cortical and peripheral arousal is not as clear as is suggested in previous research investigating both separately. Implications of these results for new treatment options for ADHD such as biofeedback are discussed.

Neurofeedback of slow cortical potentials as a treatment for adults with Attention Deficit-/Hyperactivity Disorder.

OBJECTIVE: Attention Deficit-/Hyperactivity Disorder (ADHD) has been treated successfully in children with neurofeedback (NF). In this study, for the first time NF is investigated in adults with ADHD. To answer the question of specificity the relationship between treatment outcome and self-regulation ability is assessed. METHODS: Twenty-four participants underwent 30 sessions of slow cortical potential NF. Measurements of ADHD and comorbid symptoms, as well as neurophysiological data (reaction time (RT) and RT variability (RTV) and contingent negative variation (CNV)) were performed before and after treatment, and again six months after sessions were completed. Participants were categorized into self-regulation learners and non-learners. RESULTS: Significant improvements on all symptom scales were observed with medium to large effect sizes after treatment and six months post treatment. RT and RTV decreased significantly and there was a trend for an increased CNV. Half of the participants successfully learned to regulate their brain activity. In the long-term, symptoms in the group of learners improved more than in non-learners with large effect sizes. CONCLUSION: NF is effective in treating adult ADHD long-term. The impact of self-regulation ability and possible unspecific effects still require further investigation. SIGNIFICANCE: This study is the first to investigate the effects of NF in adults with ADHD, relating clinical outcome to self-regulation performance.

Neurofeedback as a nonpharmacological treatment for adults with attention-deficit/hyperactivity disorder (ADHD): study protocol for a randomized controlled trial.

BACKGROUND: Neurofeedback has been applied effectively in various areas, especially in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This study protocol is designed to investigate the effect of slow cortical potential (SCP) feedback and a new form of neurofeedback using near-infrared spectroscopy (NIRS) on symptomatology and neurophysiological parameters in an adult ADHD population. A comparison of SCP and NIRS feedback therapy methods has not been previously conducted and may yield valuable findings about alternative treatments for adult ADHD. METHODS/DESIGN: The outcome of both neurofeedback techniques will be assessed over 30 treatment sessions and after a 6-month follow-up period, and then will be compared to a nonspecific biofeedback treatment. Furthermore, to investigate if treatment effects in this proof-of-principle study can be predicted by specific neurophysiological baseline parameters, regression models will be applied. Finally, a comparison with healthy controls will be conducted to evaluate deviant pretraining neurophysiological parameters, stability of assessment measures, and treatment outcome. DISCUSSION: To date, an investigation and comparison of SCP and NIRS feedback training to an active control has not been conducted; therefore, we hope to gain valuable insights in effects and differences of these types of treatment for ADHD in adults. TRIAL REGISTRATION: This study is registered with the German Registry of Clinical Trials: DRKS00006767 , date of registration: 8 October 2014.

Brain self-regulation in criminal psychopaths.

Psychopathic individuals are characterized by impaired affective processing, impulsivity, sensation-seeking, poor planning skills and heightened aggressiveness with poor self-regulation. Based on brain self-regulation studies using neurofeedback of Slow Cortical Potentials (SCPs) in disorders associated with a dysregulation of cortical activity thresholds and evidence of deficient cortical functioning in psychopathy, a neurobiological approach seems to be promising in the treatment of psychopathy. The results of our intensive brain regulation intervention demonstrate, that psychopathic offenders are able to gain control of their brain excitability over fronto-central brain areas. After SCP self-regulation training, we observed reduced aggression, impulsivity and behavioral approach tendencies, as well as improvements in behavioral-inhibition and increased cortical sensitivity for error-processing. This study demonstrates improvements on the neurophysiological, behavioral and subjective level in severe psychopathic offenders after SCP-neurofeedback training and could constitute a novel neurobiologically-based treatment for a seemingly change-resistant group of criminal psychopaths.

Motor skill failure or flow-experience? Functional brain asymmetry and brain connectivity in elite and amateur table tennis players.

Functional hemispheric asymmetry is assumed to constitute one underlying neurophysiological mechanism of flow-experience and skilled psycho-motor performance in table tennis athletes. We hypothesized that when initiating motor execution during motor imagery, elite table tennis players show higher right- than left-hemispheric temporal activity and stronger right temporal-premotor than left temporal-premotor theta coherence compared to amateurs. We additionally investigated, whether less pronounced left temporal cortical activity is associated with more world rank points and more flow-experience. To this aim, electroencephalographic data were recorded in 14 experts and 15 amateur table tennis players. Subjects watched videos of an opponent serving a ball and were instructed to imagine themselves responding with a specific table tennis stroke. Alpha asymmetry scores were calculated by subtracting left from right hemispheric 8-13 Hz alpha power. 4-7 Hz theta coherence was calculated between temporal (T3/T4) and premotor (Fz) cortex. Experts showed a significantly stronger shift towards lower relative left-temporal brain activity compared to amateurs and a significantly stronger right temporal-premotor coherence than amateurs. The shift towards lower relative left-temporal brain activity in experts was associated with more flow-experience and lower relative left temporal activity was correlated with more world rank points. The present findings suggest that skilled psycho-motor performance in elite table tennis players reflect less desynchronized brain activity at the left hemisphere and more coherent brain activity between fronto-temporal and premotor oscillations at the right hemisphere. This pattern probably reflect less interference of irrelevant communication of verbal-analytical with motor-control mechanisms which implies flow-experience and predict world rank in experts.

What learning theories can teach us in designing neurofeedback treatments.

Popular definitions of neurofeedback point out that neurofeedback is a process of operant conditioning which leads to self-regulation of brain activity. Self-regulation of brain activity is considered to be a skill. The aim of this paper is to clarify that not only operant conditioning plays a role in the acquisition of this skill. In order to design the learning process additional references have to be derived from classical conditioning, two-process-theory and in particular from skill learning and research into motivational aspects. The impact of learning by trial and error, cueing of behavior, feedback, reinforcement, and knowledge of results as well as transfer of self-regulation skills into everyday life will be analyzed in this paper. In addition to these learning theory basics this paper tries to summarize the knowledge about acquisition of self-regulation from neurofeedback studies with a main emphasis on clinical populations. As a conclusion it is hypothesized that learning to self-regulate has to be offered in a psychotherapeutic, i.e., behavior therapy framework.

Winning the game: brain processes in expert, young elite and amateur table tennis players.

THIS STUDY TESTED TWO HYPOTHESES: (1) compared with amateurs and young elite, expert table tennis players are characterized by enhanced cortical activation in the motor and fronto-parietal cortex during motor imagery in response to table tennis videos; (2) in elite athletes, world rank points are associated with stronger cortical activation. To this aim, electroencephalographic data were recorded in 14 expert, 15 amateur and 15 young elite right-handed table tennis players. All subjects watched videos of a serve and imagined themselves responding with a specific table tennis stroke. With reference to a baseline period, power decrease/increase of the sensorimotor rhythm (SMR) during the pretask- and task period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding hypothesis (1), 8-10 Hz SMR ERD was stronger in elite athletes than in amateurs with an intermediate ERD in young elite athletes in the motor cortex. Regarding hypothesis (2), there was no correlation between ERD/ERS in the motor cortex and world rank points in elite experts, but a weaker ERD in the fronto-parietal cortex was associated with higher world rank points. These results suggest that motor skill in table tennis is associated with focused excitability of the motor cortex during reaction, movement planning and execution with high attentional demands. Among elite experts, less activation of the fronto-parietal attention network may be necessary to become a world champion.

Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a controlled multicenter study of a non-pharmacological treatment approach.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta-analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities. METHODS/DESIGN: A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) -feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal. DISCUSSION: The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated. TRIALS REGISTRATION: Current Controlled Trials ISRCTN76187185. Registered 5 February 2009.

Sustained reduction of seizures in patients with intractable epilepsy after self-regulation training of slow cortical potentials - 10 years after.

The aim of this study was to determine whether the reduction of seizures in patients with intractable epilepsy after self-regulation of slow cortical potentials (SCPs) was maintained almost 10 years after the end of treatment. Originally, 41 patients received training with SCP-neurofeedback. A control group of 12 patients received respiratory feedback while another group of 11 patients had their anticonvulsant medications reviewed. Nineteen patients in the experimental group participated at least in parts of the long-term follow-up, but only two patients from each control group agreed to do so. The follow-up participants completed the same seizure diaries as in the original study. Patients of the experimental group also took part in three SCP-training sessions at the follow-up evaluation. Due to the small sample size, the results of participants in the control groups were not considered in the analysis. A significant decrease in seizure frequency was found about 10 years after the end of SCP treatment. The clinical significance of this result is considered medium to high. All patients were still able to self-regulate their SCPs during the feedback condition. This success was achieved without booster sessions. This is the longest follow-up evaluation of the outcome of a psychophysiological treatment in patients with epilepsy ever reported. Reduced seizure frequency may be the result of patients continued ability to self-regulate their SCPs. Given such a long follow-up period, the possible impact of confounding variables should be taken into account. The small number of patients participating in this follow-up evaluation diminishes the ability to make causal inferences. However, the consistency and duration of improvement for patients who received SCP-feedback training suggests that such treatment may be considered as a treatment for patients with intractable epilepsy and as an adjunct to conventional therapies.