Accelerating P300-based neurofeedback training for attention enhancement using iterative learning control: a randomised controlled trial.

Objective. Neurofeedback (NFB) training through brain-computer interfacing has demonstrated efficacy in treating neurological deficits and diseases, and enhancing cognitive abilities in healthy individuals. It was previously shown that event-related potential (ERP)-based NFB training using a P300 speller can improve attention in healthy adults by incrementally increasing the difficulty of the spelling task. This study aims to assess the impact of task difficulty adaptation on ERP-based attention training in healthy adults. To achieve this, we introduce a novel adaptation employing iterative learning control (ILC) and compare it against an existing method and a control group with random task difficulty variation.Approach. The study involved 45 healthy participants in a single-blind, three-arm randomised controlled trial. Each group underwent one NFB training session, using different methods to adapt task difficulty in a P300 spelling task: two groups with personalised difficulty adjustments (our proposed ILC and an existing approach) and one group with random difficulty. Cognitive performance was evaluated before and after the training session using a visual spatial attention task and we gathered participant feedback through questionnaires.Main results. All groups demonstrated a significant performance improvement in the spatial attention task post-training, with an average increase of 12.63%. Notably, the group using the proposed iterative learning controller achieved a 22% increase in P300 amplitude during training and a 17% reduction in post-training alpha power, all while significantly accelerating the training process compared to other groups.Significance. Our results suggest that ERP-based NFB training using a P300 speller effectively enhances attention in healthy adults, with significant improvements observed after a single session. Personalised task difficulty adaptation using ILC not only accelerates the training but also enhances ERPs during the training. Accelerating NFB training, while maintaining its effectiveness, is vital for its acceptability by both end-users and clinicians.

Effect of a single session of sensorimotor rhythm neurofeedback training on the putting performance of professional golfers.

Sensorimotor rhythm (SMR) activity has been associated with automaticity and flow in motor execution. Studies have revealed that neurofeedback training (NFT) of the SMR can improve sports performance; however, few studies have adequately explored the effects of a single session of such NFT or examined the possible mechanisms underlying these effects on sports performance. This study recruited 44 professional golfers to address these gaps in the literature. A crossover design was employed to determine the order of the participation in the NFT and no-training control conditions. The participants were asked to perform 60 10-foot putts while electroencephalograms (EEGs) were recorded before and after the tasks. In pre-and post-tests, visual analog scales were used to assess the psychological states associated with SMR activities including the levels of attention engagement, conscious motor control, and physical relaxation. The results revealed that a single NFT session effectively increased SMR power and improved putting performance compared with the control condition. The subjective assessments also revealed that the participants reported lower attention engagement, less conscious control of the motor details and were more relaxed in the putting task, suggesting that SMR NFT promoted effortless and quiescent mental states during motor preparation for a putting task. This study aligns with theoretical hypotheses and extends current knowledge by revealing that a single session of SMR NFT can effectively enhance SMR power and improve putting performance in professional golfers. It also provides preliminary evidence of the possible underlying mechanisms that drive the effect of SMR NFT on putting performances.

Distinct effects of different neurofeedback protocols on the neural mechanisms of response inhibition in ADHD.

OBJECTIVE: In attention deficit/hyperactivity disorder (ADHD), impaired response inhibition is frequently observed. A promising non-pharmacological treatment is electroencephalography (EEG)-neurofeedback (NF) training. However, the widely used theta-down/beta-up regulation (↓θ↑ß) NF protocol may not be optimal for targeting these deficits. We examined how neurofeedback protocols training the upregulation of theta and/or beta power affect inhibitory control in children and adolescents with ADHD. METHODS: 64 patients with ADHD took part in the three NF trainings. Aside from parent-reported ADHD symptoms and behavioural performance data, neurophysiological parameters collected via a Go/Nogo task and corrected to account for intraindividual variability were compared in a pre-post design and to an ADHD (n = 20) as well as a typically developing control group (n = 24). RESULTS: The examined NF protocols resulted in similar improvements in response inhibition with the neurophysiological mechanisms differing substantially. The upregulation of theta led to a specific Nogo-P3 increase, while training beta upregulation as well as the combined protocol resulted in less specific effects. CONCLUSIONS: This study shows distinct effects of different theta/beta-neurofeedback protocols on the neural mechanisms underlying improvements in response inhibition in patients with ADHD. SIGNIFICANCE: These effects shed further light on the oscillatory dynamics underlying cognitive control in ADHD and how these may be targeted in neurofeedback treatments.

The Effect of Neurofeedback Training on Executive Control Network of Attention and Dart-Throwing Performance in Individuals with Trait Anxiety.

This study aimed to investigate the effect of neurofeedback training on the executive control network of attention and dart-throwing skill performance in individuals with trait anxiety. Twenty girls (24.65 [Formula: see text] 2.83 years) participated in this study. They were divided into neurofeedback and control training groups. All participants practiced 14 sessions. The neurofeedback group performed neurofeedback training (increasing SMR wave, decreasing theta, and increasing alpha) and dart-throwing exercise, and the control group only completed the dart-throwing exercise. The post-test, including Attentional Networks Test (ANT) and dart-throwing, was conducted 48 h after the last training session. The results revealed a significant difference in the performance of the executive control network and dart-throwing skill between the neurofeedback and the control training group. In general, these findings support the effect of neurofeedback training on the neural mechanisms of the executive control network of attention, and performance in dart-throwing skill improves by improving attentional performance processes.

Effects of neurofeedback training on performance in laboratory tasks: A systematic review.

Neurofeedback procedures are attracting increasing attention in the neuroscience community. Based on the principle that participants, through suitable feedback, may learn to affect specific aspects of their brain activity, neurofeedback interventions have been applied to basic research, translational, and clinical science. A large segment of the available empirical research as well as review articles have focused on the extent to which neurofeedback interventions affect mental health outcomes, cognitive capacity, aging, and other complex behaviors. Another segment has aimed to characterize the extent to which neurofeedback affects the targeted neural processes. At this time, there is no current systematic review of the effects of neurofeedback on healthy participants' performance in experimental tasks. Such a review is relevant in this rapidly evolving field because changes in experimental task performance are traditionally considered a hallmark of changing neurocognitive processes, often established in neurotypical individuals. This systematic review addresses this gap in the literature using the PRISMA method, building on earlier reviews on the same topic. Empirical studies using EEG or fMRI to alter brain processes linked to established cognitive and affective laboratory tasks were reviewed. Systematic quality assessment and z-curve analyses were also conducted. Substantial variability was found regarding the study designs used, the implementation of the feedback, and the neural targets of feedback. Importantly, only a minority of the studies reported statistically meaningful effects of neurofeedback on performance in cognitive and affective tasks. The z-curve analyses found no evidence for reporting bias or unsound research practices. Quality control and effect size analyses showed few systematic relations between study characteristics such as sample size or experimental control on the one hand and outcome on the other. Overall, the present study does not support strong effects of NFT on performance in laboratory tasks. Implications for future work are discussed.

Remote neurocognitive interventions for attention-deficit/hyperactivity disorder - Opportunities and challenges.

Improving neurocognitive functions through remote interventions has been a promising approach to developing new treatments for attention-deficit/hyperactivity disorder (AD/HD). Remote neurocognitive interventions may address the shortcomings of the current prevailing pharmacological therapies for AD/HD, e.g., side effects and access barriers. Here we review the current options for remote neurocognitive interventions to reduce AD/HD symptoms, including cognitive training, EEG neurofeedback training, transcranial electrical stimulation, and external cranial nerve stimulation. We begin with an overview of the neurocognitive deficits in AD/HD to identify the targets for developing interventions. The role of neuroplasticity in each intervention is then highlighted due to its essential role in facilitating neuropsychological adaptations. Following this, each intervention type is discussed in terms of the critical details of the intervention protocols, the role of neuroplasticity, and the available evidence. Finally, we offer suggestions for future directions in terms of optimizing the existing intervention protocols and developing novel protocols.

Magnetoencephalographic neurofeedback training decreasesß-low-γphase-amplitude coupling of the motor cortex of healthy adults: a double-blinded randomized crossover feasibility study.

Objective.The coupling between the beta (13-30 Hz) phase and low gamma (50-100 Hz) amplitude in the motor cortex is thought to regulate motor performance. Abnormal phase-amplitude coupling (PAC) of beta-low gamma (ß-low-γPAC) is associated with motor symptoms of Parkinson's disease. However, the causal relationship betweenß-low-γPAC and motor performance in healthy subjects is unknown. We hypothesized that healthy subjects could change the strength of theß-low-γPAC in the resting state by neurofeedback training (NFT) to control theß-low-γPAC, such that the motor performance changes in accordance with the changes inß-low-γPAC in the resting state.Approach.We developed an NFT to control the strength of theß-low-γPAC in the motor cortex, which was evaluated by magnetoencephalography (MEG) using a current source estimation technique. Twenty subjects were enrolled in a double-blind randomized crossover trial to test the feasibility of the MEG NFT. In the NFT for 2 d, the subjects were instructed to reduce the size of a black circle whose radius was proportional (down-training) or inversely proportional (up-training) to the strength of theß-low-γPAC. The reaction times (RTs) to press a button according to some cues were evaluated before and after training. This study was registered at ClinicalTrials.gov (NCT03837548) and UMIN-CTR (UMIN000032937).Main results.Theß-low-γPAC during the resting state was significantly decreased after down-training, although not significantly after up-training. RTs tended to decrease after both trainings, however the differences were not statistically significant. There was no significant correlation between the changes inß-low-γPAC during rest and RTs.Significance.The proposed MEG NFT was demonstrated to change theß-low-γPAC of the motor cortex in healthy subjects. However, a relationship between PAC and RT has not yet been demonstrated.

An investigation of the effectiveness of neurofeedback training on motor performance in healthy adults: A systematic review and meta-analysis.

Neurofeedback training (NFT) refers to a training where the participants voluntarily aim to manipulate their own brain activity using the sensory feedback abstracted from their brain activity. NFT has attracted attention in the field of motor learning due to its potential as an alternative or additional training method for general physical training. In this study, a systematic review of NFT studies for motor performance improvements in healthy adults and a meta-analysis on the effectiveness of NFT were conducted. A computerized search was performed using the databases Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web to identify relevant studies published between January 1st, 1990, and August 3rd, 2021. Thirty-three studies were identified for the qualitative synthesis and 16 randomized controlled trials (374 subjects) for the meta-analysis. The meta-analysis, including all trials found in the search, revealed significant effects of NFT for motor performance improvement examined at the timing after the last NFT session (standardized mean difference = 0.85, 95% CI [0.18-1.51]), but with the existence of publication biases and substantial heterogeneity among the trials. Subsequent meta-regression analysis demonstrated the dose-response gradient between NFTs and motor performance improvements; more than 125 min of cumulative training time may benefit for the subsequent motor performance. For each motor performance measure (e.g., speed, accuracy, and hand dexterity), the effectiveness of NFT remains inconclusive, mainly due to its small sample sizes. More empirical NFT studies for motor performance improvement may be needed to show beneficial effects on motor performance and to safely incorporate NFT into real-world scenarios.

Neurofeedback Training without Explicit Phantom Hand Movements and Hand-Like Visual Feedback to Modulate Pain: A Randomized Crossover Feasibility Trial.

Phantom limb pain is attributed to abnormal sensorimotor cortical representations, although the causal relationship between phantom limb pain and sensorimotor cortical representations suffers from the potentially confounding effects of phantom hand movements. We developed neurofeedback training to change sensorimotor cortical representations without explicit phantom hand movements or hand-like visual feedback. We tested the feasibility of neurofeedback training in fourteen patients with phantom limb pain. Neurofeedback training was performed in a single-blind, randomized, crossover trial using two decoders constructed using motor cortical currents measured during phantom hand movements; the motor cortical currents contralateral or ipsilateral to the phantom hand (contralateral and ipsilateral training) were estimated from magnetoencephalograms. Patients were instructed to control the size of a disk, which was proportional to the decoding results, but to not move their phantom hands or other body parts. The pain assessed by the visual analogue scale was significantly greater after contralateral training than after ipsilateral training. Classification accuracy of phantom hand movements significantly increased only after contralateral training. These results suggested that the proposed neurofeedback training changed phantom hand representation and modulated pain without explicit phantom hand movements or hand-like visual feedback, thus showing the relation between the phantom hand representations and pain. PERSPECTIVE: Our work demonstrates the feasibility of using neurofeedback training to change phantom hand representation and modulate pain perception without explicit phantom hand movements and hand-like visual feedback. The results enhance the mechanistic understanding of certain treatments, such as mirror therapy, that change the sensorimotor cortical representation.

Neurofeedback and neural self-regulation: a new perspective based on allostasis.

The field of neurofeedback training (NFT) has seen growing interest and an expansion of scope, resulting in a steadily increasing number of publications addressing different aspects of NFT. This development has been accompanied by a debate about the underlying mechanisms and expected outcomes. Recent developments in the understanding of psychophysiological regulation have cast doubt on the validity of control systems theory, the principal framework traditionally used to characterize NFT. The present article reviews the theoretical and empirical aspects of NFT and proposes a predictive framework based on the concept of allostasis. Specifically, we conceptualize NFT as an adaptation to changing contingencies. In an allostasis four-stage model, NFT involves (a) perceiving relations between demands and set-points, (b) learning to apply collected patterns (experience) to predict future output, (c) determining efficient set-points, and (d) adapting brain activity to the desired ("set") state. This model also identifies boundaries for what changes can be expected from a neurofeedback intervention and outlines a time frame for such changes to occur.

Neurofeedback Training of the Control Network in Children Improves Brain Computer Interface Performance.

In the past 20 years, neural engineering has made unprecedented progress in the interpretation of brain information (e.g., brain-computer interfaces) and in neuromodulation (e.g., electromagnetic stimulation and neurofeedback). However, there has been little research aiming to improve the performance of brain-computer interfaces (BCIs) using neuromodulation. The present study presents a novel design for a neurofeedback training (NFT) method to improve the operation of a steady-state visual evoked potential (SSVEP)-based BCI and further explores its underlying mechanisms. The use of NFT to upregulate alpha-band power in the user's parietal lobe is presented in this study as a new neuromodulation method to improve SSVEP-based BCI in this study. After users completed this NFT intervention, the signal-to-noise ratio (SNR), accuracy, and information transfer rate (ITR) of the SSVEP-based BCI were increased by 5.8%, 4.7%, and 15.6%, respectively. However, no improvement was observed in the control group in which the subjects did not participate in NFT. Moreover, a general reinforcement of the information flow from the parietal lobe to the occipital lobe was observed. Evidence from a network analysis and an attention test further indicates that NFT improves attention by developing the control capacity of the parietal lobe and then enhances the above SSVEP indicators. Upregulating the amplitude of parietal alpha oscillations using NFT significantly improves the SSVEP-based BCI performance by modulating the control network. The study validates an effective neuromodulation method and possibly contributes to explaining the function of the parietal lobe in the control network.

EEG-neurofeedback and executive function enhancement in healthy adults: A systematic review.

Electroencephalographic (EEG)-neurofeedback training (NFT) is a promising technique that supports individuals in learning to modulate their brain activity to obtain cognitive and behavioral improvements. EEG-NFT is gaining increasing attention for its potential "peak performance" applications on healthy individuals. However, evidence for clear cognitive performance enhancements with healthy adults is still lacking. In particular, whether EEG-NFT represents an effective technique for enhancing healthy adults' executive functions is still controversial. Therefore, the main objective of this systematic review is to assess whether the existing EEG-NFT studies targeting executive functions have provided reliable evidence for NFT effectiveness. To this end, we conducted a qualitative analysis of the literature since the limited number of retrieved studies did not allow us meta-analytical comparisons. Moreover, a second aim was to identify optimal frequencies as NFT targets for specifically improving executive functions. Overall, our systematic review provides promising evidence for NFT effectiveness in boosting healthy adults' executive functions. However, more rigorous NFT studies are required in order to overcome the methodological weaknesses that we encountered in our qualitative analysis.

From reversal to normal: Robust improvement in conflict adaptation through real-time functional near infrared spectroscopy-based neurofeedback training.

Conflict adaptation refers to the improved conflict control induced after experiencing conflict and is a prominent index of adaptive cognitive control. Reversal of conflict adaptation may be maladaptive and predictive of certain mental disorders. Here, we employed real-time functional near infrared spectroscopy-based neurofeedback training, with the left dorsolateral prefrontal cortex as the target brain area, to investigate whether reversal of conflict adaptation during a word-color Stroop task could be recovered to be normal. Healthy human individuals with reversal pattern of conflict adaptation in the pretest were randomly assigned into the experimental or control groups. Distributed training for 80 min led to greater improvements in the experimental group who received real neurofeedback compared to those in the control group who received sham neurofeedback. These results indicated causal evidence for understanding the generation of conflict adaptation and heighten the prospects of clinical application of neurofeedback training.

Review of Neuropsychological and Electrophysiological Correlates of Callous-unemotional Traits in Children: Implications for EEG Neurofeedback Intervention.

Conduct disorder is a significant psychiatric disorder of childhood and adolescence. The Diagnostic and Statistical Manual of Mental Disorders, fifth version (DSM-5), added the limited prosocial specifier to identify those individuals who exhibit a more severe pattern of behavior characterized by a callous and unemotional (CU) interpersonal style across multiple settings and relationships. This review has attempted to summarize the relevant research focusing on the significance of CU interpersonal style in the development of psychopathy. The primary focus was on the electrophysiological and neuropsychological correlates of CU traits and their implication on the treatment protocol using neurofeedback training for children with such traits. The source of the literature search was PubMed, which majorly uses the MEDLINE database. The keywords used included CU traits, conduct disorder, child psychopathy, empathy, electrophysiology, criminal behavior, neuropsychology, neurofeedback training, and so on. Studies from the last 15 years were considered for the review. This review revealed that children with conduct disorder and high-CU traits with a combination of reactive and proactive aggression are more likely to develop psychopathy. Evidence suggests that these children have distinct forms of electrophysiological and neuropsychological correlates. However, research in this area is still not conclusive as they yield variation in findings. Studies on the efficacy of neurofeedback training on reducing symptoms such as impulsivity, hostility, and psychopathy indicate that neurofeedback training can be a promising treatment alternative for children with severe conduct disorder.

Session Frequency Matters in Neurofeedback Training of Athletes.

Neurofeedback training has been an increasingly used technique and is taking its first steps in sport. Being at an embryonic stage, it is difficult to find consensus regarding the applied methodology to achieve the best results. This study focused on understanding one of the major methodological issues-the training session frequency. The aim of the investigation was to understand if there are differences between performing two sessions or three sessions per week in enhancement of alpha activity and improvement of cognition; and in case there are differences, infer the best protocol. Forty-five athletes were randomly assigned to the three-session-training-per-week group, the two-session-training-per-week group and a control group. The results showed that neurofeedback training with three sessions per week was more effective in increase of alpha amplitude during neurofeedback training than two sessions per week. Furthermore, only the three-session-per-week group showed significant enhancement in N-back and oddball performance after training. The findings suggested more condensed training protocol lead to better outcomes, providing guidance on neurofeedback protocol design in order to optimize training efficacy.

Electroencephalogram-based neurofeedback training in persons with stroke: A scoping review in occupational therapy.

BACKGROUND: Neurofeedback training targets the relevant brain response under minimal stress. It could be a promising approach for the treatment of patients with brain injury. OBJECTIVE: This review aimed to examine the existing literature to confirm the effectiveness of applied electroencephalogram (EEG)-based neurofeedback training in the area of occupational therapy for upper limb stroke rehabilitation. METHOD: All relevant literature published until July 1, 2020 in five prominent databases (PubMed, CINAHL, PsycINFO, MEDLINE Complete, and Web of Science) was reviewed, based on the five-step review framework proposed by Arksey and O'Malley. RESULTS: After a thorough review, a total of 14 studies were included in this review. Almost studies reported significant improvements as a result of EEG-based neurofeedback training, but this had not always account for the differences in effectiveness between groups. However, the results of these studies suggested that neurofeedback training was effective as compared to the traditional treatment and more effective in combination with EEG than that with simple equipment application. CONCLUSION: This review demonstrated the effectiveness of the combination of occupational therapy and EEG-based neurofeedback training. Most of these treatments are intended for inpatients, but they may be more effective for outpatients, especially if customized to their requirements. Also, such explorations to assess the suitability of the treatment for patient rehabilitation will help reduce barriers to effective interventions. An analysis of the opinions of participants and experts through satisfaction surveys will be helpful.

Soft boundary-based neurofeedback training based on fuzzy similarity measures: A method for learning how to control EEG Signal features during neurofeedback training.

BACKGROUND: Most commonly used neurofeedback training (NFT) methods are able to assist subjects towards an increase/decrease in EEG features. So, it is possible that the enhancement/inhabitation in a subject's EEG features exceed normal limits if the process of changes in brain activity in the subject is very successful. This issue may also bring about a reduction in the effectiveness of NFT. NEW METHOD: A soft boundary-based NFT method was proposed for learning how to control the EEG features during training. According to this method, an initial group was defined within which the training features of subjects' EEG signals were placed prior to training and a target group was considered referring to what the features of the EEG signals should be shifted towards during training. In the course of training, the fuzzy similarity of EEG features of subject towards the target group center was measured and the subject's score was increased if their fuzzy similarity was higher than a threshold. Within this method, an adaptive scoring index (the scores assigned to subjects for each achievement) was defined whose value was determined according to brain activity of the subject. RESULTS: Increase/decrease in large amounts in the training features of subject's EEG could lead to a descending trend in the scores received using the proposed method. COMPARISON WITH EXISTING METHODS: The proposed method may assist subjects to control their EEG signal features within the target group range. CONCLUSION: The proposed method may be able to prevent the side effects of neurofeedback.

Brain-Computer Interface Design and Neurofeedback Training in the Case of ADHD Rehabilitation.

Neurofeedback video games respond to electrical brain signals instead to a mouse, joystick, or game controller input. These games embody the concept of improving physiological functioning by rewarding specific healthy body signals with success at playing a video game. In this paper, a threefold framework in reference to attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) treatment blending with neurofeedback techniques and video game implementation is presented. In particular, the specifications of a neurofeedback-based video game for children dealing with ADHD, in order to enhance attention and concentration skills, are analyzed. Potential boundaries of this cognitive enhancement approach and authors future directions are also discussed.

Neurofeedback-Linked Suppression of Cortical ß Bursts Speeds Up Movement Initiation in Healthy Motor Control: A Double-Blind Sham-Controlled Study.

Abnormally increased ß bursts in cortical-basal ganglia-thalamic circuits are associated with rigidity and bradykinesia in patients with Parkinson's disease. Increased ß bursts detected in the motor cortex have also been associated with longer reaction times (RTs) in healthy participants. Here we further hypothesize that suppressing ß bursts through neurofeedback training can improve motor performance in healthy subjects. We conducted a double-blind sham-controlled study on 20 human volunteers (10 females) using a sequential neurofeedback-behavior task with the neurofeedback reflecting the occurrence of ß bursts over sensorimotor cortex quantified in real time. The results show that neurofeedback training helps healthy participants learn to volitionally suppress ß bursts in the sensorimotor cortex, with training being accompanied by reduced RT in subsequent cued movements. These changes were only significant in the real feedback group but not in the sham group, confirming the effect of neurofeedback training over simple motor imagery. In addition, RTs correlated with the rate and accumulated duration of ß bursts in the contralateral motor cortex before the go-cue, but not with averaged ß power. The reduced RTs induced by neurofeedback training positively correlated with reduced ß bursts across all tested hemispheres. These results strengthen the link between the occurrence of ß bursts in the sensorimotor cortex before the go-cue and slowed movement initiation in healthy motor control. The results also highlight the potential benefit of neurofeedback training in facilitating voluntary suppression of ß bursts to speed up movement initiation.SIGNIFICANCE STATEMENT This double-blind sham-controlled study suggested that neurofeedback training can facilitate volitional suppression of ß bursts in sensorimotor cortex in healthy motor control better than sham feedback. The training was accompanied by reduced reaction time (RT) in subsequent cued movements, and the reduced RT positively correlated with the level of reduction in cortical ß bursts before the go-cue, but not with average ß power. These results provide further evidence of a causal link between sensorimotor ß bursts and movement initiation and suggest that neurofeedback training could potentially be used to train participants to speed up movement initiation.

Treatment of Neurodegeneration: Integrating Photobiomodulation and Neurofeedback in Alzheimer's Dementia and Parkinson's: A Review.

Objective: A review of photobiomodulation (PBM) in Alzheimer's dementia is submitted. The addition of PBM in neurodegenerative diseases is a dual modality that is at present gaining traction as it is safe, antiviral, and anti-inflammatory for treating neurodegeneration with photons that stimulate mitochondria increasing adenosine triphosphate and proteasomes increasing misfolded protein removal. Neurofeedback provides neural plasticity with an increase in brain-derived nerve factor mRNA and an increase in dendrite production and density in the hippocampus coupled with overall growth in dendrites, density, and neuronal survival. Background: Alzheimer's disease pathophysiology is the accumulation of hyperphosphorylated tau protein neurofibrillary tangles and subsequently amyloid-beta (Aß) plaques. PBM and neurobiofeedback (NBF)address the multiple gene expression and upregulation of multiple pathogenic pathway inflammation, reactive oxidative stress, mitochondrial disorders, insulin resistance, methylation defects, regulation of neuroprotective factors, and regional hypoperfusion of the brain. There is no human evidence to suggest a clinical therapeutic benefit from using consistent light sources while significantly increasing safety concerns. Methods: A PBM test with early- to mid-Alzheimer's was reported in 2017, consisting of a double-blind, placebo-controlled trial in a small pilot group of early- to mid-dementia subjects under Institutional Review Board (IRB)-approved Food and Drug Administration (FDA) Clinical Trial. Results: PBM-treated subjects showed that active treatment subjects tended to show greater improvement in the functioning of the executive: clock drawing, immediate recall, practical memory, and visual attention and task switching (Trails A&B). A larger study using the CerebroLite helmet in Temple Texas again of subjects in a double-blind, placebo-controlled IRB-approved FDA Clinical Trial demonstrated gain in memory and cognition by increased clock drawing. Conclusions: Next-generation trials with the Cognitolite for Parkinson's disease subjects will incorporate the insights regarding significant bilateral occipital hypocoherence deficits gained from the quantitative EEG analyses. Future applications will integrate noninvasive stimulation delivery, including full-body and transcranial and infrared light with pulsed electromagnetic frequencies.