A Scoping Review of the Effect of EEG Neurofeedback on Pain Complaints in Adults with Chronic Pain.

Background and Aim: Non-pharmacological treatments such as electroencephalogram (EEG) neurofeedback have become more important in multidisciplinary approaches to treat chronic pain. The aim of this scoping review is to identify the literature on the effects of EEG neurofeedback in reducing pain complaints in adult chronic-pain patients and to elaborate on the neurophysiological rationale for using specific frequency bands as targets for EEG neurofeedback. Methods: A pre-registered scoping review was set up and reported following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for Scoping Reviews (PRISMA-ScR). The data were collected by searching for studies published between 1985 and January 2023 in PubMed, EMBASE, and PsycINFO. Results: Thirty-two studies on various types of chronic pain were included. The intervention was well-tolerated. Approximately half of the studies used a protocol that reinforced alpha or sensorimotor rhythms and suppressed theta or beta activity. However, the underlying neurophysiological rationale behind these specific frequency bands remains unclear. Conclusions: There are indications that neurofeedback in patients with chronic pain probably has short-term analgesic effects; however, the long-term effects are less clear. In order to draw more stable conclusions on the effectiveness of neurofeedback in chronic pain, additional research on the neurophysiological mechanisms of targeted frequency bands is definitely worthwhile. Several recommendations for setting up and evaluating the effect of neurofeedback protocols are suggested.

Habituation to pain: self-report, electroencephalography, and functional magnetic resonance imaging in healthy individuals. A scoping review and future recommendations.

ABSTRACT: Habituation to pain is a fundamental learning process and important adaption. Yet, a comprehensive review of the current state of the field is lacking. Through a systematic search, 63 studies were included. Results address habituation to pain in healthy individuals based on self-report, electroencephalography, or functional magnetic resonance imaging. Our findings indicate a large variety in methods, experimental settings, and contexts, making habituation a ubiquitous phenomenon. Habituation to pain based on self-report studies shows a large influence of expectations, as well as the presence of individual differences. Furthermore, widespread neural effects, with sometimes opposing effects in self-report measures, are noted. Electroencephalography studies showed habituation of the N2-P2 amplitude, whereas functional magnetic resonance imaging studies showed decreasing activity during painful repeated stimulation in several identified brain areas (cingulate cortex and somatosensory cortices). Important considerations for the use of terminology, methodology, statistics, and individual differences are discussed. This review will aid our understanding of habituation to pain in healthy individuals and may lead the way to improving methods and designs for personalized treatment approaches in chronic pain patients.

Habituation to Pain in Patients with Chronic Pain: Clinical Implications and Future Directions.

In this review, the latest insights into habituation to pain in chronic pain are summarized. Using a systematic search, results of studies on the evidence of habituation to (experimental) pain in migraine, chronic low back pain, fibromyalgia, and a variety of chronic pain indications are presented. In migraine, reduced habituation based on self-report and the EEG-based N1 and N2-P2 amplitude is reported, but the presence of contradictory results demands further replication in larger, well-designed studies. Habituation to pain in chronic low back pain seems not to differ from controls, with the exception of EEG measures. In fibromyalgia patients, there is some evidence for reduced habituation of the N2-P2 amplitude. Our analysis shows that the variability between outcomes of studies on habituation to pain is high. As the mechanisms underlying habituation to pain are still not fully understood and likely involve several pathways, it is now too early to conclude that habituation to pain is related to clinical outcomes and can be used as a diagnostic marker. The review ends with a discussion on future directions for research including the use of standard outcome measures to improve comparisons of habituation to pain in patients and controls, as well as a focus on individual differences.

Does baseline EEG activity differ in the transition to or from a chronic pain state? A longitudinal study.

BACKGROUND AND AIM: Identifying EEG brain markers might yield better mechanistic insights into how chronic pain develops and could be treated. An existing longitudinal EEG study gave us the opportunity to determine whether the development of pain is accompanied by less alpha power-ie, a "relaxed" brain state-and vice versa. METHODS: Five-minute resting EEG with the eyes open was measured 2 times in 95 subjects at T0 (baseline) and T1 (6 months later). Based on the Short-Form Health Survey and Brief Pain Inventory questionnaire, subjects were divided into 4 groups: staying pain-free (n = 44), developing chronic pain (n = 8), becoming pain-free (n = 15), and ongoing chronic pain (n = 28). The EEG data of 14 electrodes were analyzed by multilevel regression. RESULTS: The group that developed chronic pain demonstrated less power in the lower-frequency bands over time during the resting state EEG, whereas the transition to a pain-free state had the opposite pattern. Thus, the a priori hypothesis was confirmed. CONCLUSIONS: Transitions in pain states are linked to a change in baseline EEG activity. Future research is needed to replicate these results in a larger study sample and in targeted clinical populations. Furthermore, these results might be beneficial in optimizing neurofeedback algorithms for the treatment of chronic pain.

Does pain hypervigilance further impact the lack of habituation to pain in individuals with chronic pain? A cross-sectional pain ERP study.

AIM: In chronic pain, habituation is believed to be impaired, and pain hypervigilance can enhance the pain experience. The goal of this study was to determine whether pain hypervigilance further worsens habituation of event-related potentials, measured in a pain-rating protocol of 25 painful somatosensory electrical stimuli, in patients with chronic pain. METHODS: Pain hypervigilance was assessed with the Pain Vigilance Awareness Questionnaire and analyzed using the event-related fixed interval areas multilevel technique, which enables one to study within-session habituation. In a cohort of 111 participants, 33 reported chronic pain. This chronic pain group was compared with 33 pain-free individuals, matched for age and sex. RESULTS: The relationship between pain status and habituation was not moderated by pain hypervigilance. Chronic pain status affected linear habituation and dishabituation (quadratic function) from 220 to 260 ms for nearly all electrodes, and from 580 to 640 ms for frontal electrodes. The effect of pain hypervigilance on habituation was observed primarily from 480 to 820 ms poststimulus for right-sided and central electrodes. CONCLUSION: Pain hypervigilance and chronic pain independently influence habituation to painful stimuli - although not synergistically. To confirm that these effects are mediated by separate pathways, further research is required, in which electroencephalography is combined with other modalities with adequate spatial resolution, such as functional magnetic resonance imaging.

Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.

The Influence of Perceived Stress on Cortical Reactivity: A Proof-Of-Principle Study.

The aim of this study was to investigate how perceived stress may affect electroencephalographical (EEG) activity in a stress paradigm in a sample of 76 healthy participants. EEG activity was analyzed using multilevel modeling, allowing estimation of nested effects (EEG time segments within subjects). The stress paradigm consisted of a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. At t=3 minutes, a single electrical stimulus was delivered. Participants were unaware of the precise moment of stimulus delivery and its intensity level. In the EEG time course of alpha activity, a stronger increase was observed during the post-stimulus period as compared to the pre-stimulus period. An opposite time course effect was apparent for gamma activity. Both effects were in line with a priori expectations and support the validity of this experimental EEG-stress paradigm. Secondly, we investigated whether interaction effects of stress and coping, as measured with the Perceived Stress Scale-10 questionnaire (PSS-10), could be demonstrated. A higher perceived stress score was accompanied by a greater increase in delta- and theta-activity during the post-stimulus phase, compared to low scores. In contrast, low coping capacity was associated with a stronger decrease in slow beta, fast beta and gamma activity during the post-stimulus phase. The results of the present article may be interpreted as proof-of-principle that EEG stress-related activity depends on the level of subjectively reported perceived stress. The inclusion of psychosocial variables measuring coping styles as well as stress-related personality aspects permits further examination of the interconnection between mind and body and may inform on the process of transformation from acute to chronic stress.

Does habituation differ in chronic low back pain subjects compared to pain-free controls? A cross-sectional pain rating ERP study reanalyzed with the ERFIA multilevel method.

The objective of the present study was to investigate cortical differences between chronic low back pain (CLBP) subjects and pain-free controls with respect to habituation and processing of stimulus intensity. The use of a novel event-related fixed-interval areas (ERFIA) multilevel technique enables the analysis of event-related electroencephalogram (EEG) of the whole post stimulus range at a single trial level. This technique makes it possible to disentangle the cortical processes of habituation and stimulus intensity.In a cross-sectional study, 78 individuals with CLBP and 85 pain-free controls underwent a rating paradigm of 150 nonpainful and painful somatosensory electrical stimuli. For each trial, the entire epoch was partitioned into 20-ms ERFIAs, which acted as dependent variables in a multilevel analysis. The variability of each consecutive ERFIA period was modeled with a set of predictor variables, including 3 forms of habituation and stimulus intensity.Seventy-six pain-free controls and 65 CLBP subjects were eligible for analysis. CLBP subjects showed a significantly decreased linear habituation at 340 to 460 ms in the midline electrodes and C3 (Ps < .05) and had a significantly more pronounced dishabituation for the regions of 400 to 460 ms and 800 to 820 ms for all electrodes, except for T3 and T4 (Ps < .05). No significant group differences for stimulus intensity processing were observed.In this study, group differences with respect to linear habituation and dishabituation were demonstrated. By means of the ERFIA multilevel technique, habituation effects were found in a broad post stimulus range and were not solely limited to peaks. This study suggests that habituation may be a key mechanism involved in the transition process to chronic pain. Future studies with a longitudinal design are required to solve this issue.

Experimentally induced stress validated by EMG activity.

Experience of stress may lead to increased electromyography (EMG) activity in specific muscles compared to a non-stressful situation. The main aim of this study was to develop and validate a stress-EMG paradigm in which a single uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity of the trapezius muscles was the response of interest. In addition to linear time effects, non-linear EMG time courses were also examined. Taking into account the hierarchical structure of the dataset, a multilevel random regression model was applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3-minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. EMG activity during the entire experiment was conform a priori expectations: the pre-stimulus phase showed a significantly higher mean EMG activity level compared to the other two phases, and an immediate EMG response to the stimulus was demonstrated. In addition, the analyses revealed significant non-linear EMG time courses in all three phases. Linear and quadratic EMG time courses were significantly modified by subjective anticipatory stress level, measured just before the start of the stress task. Linking subjective anticipatory stress to EMG stress reactivity revealed that subjects with a high anticipatory stress level responded with more EMG activity during the pre-stimulus stress phase, whereas subjects with a low stress level showed an inverse effect. Results suggest that the stress paradigm presented here is a valid test to quantify individual differences in stress susceptibility. Further studies with this paradigm are required to demonstrate its potential use in mechanistic clinical studies.

Introducing the event related fixed interval area (ERFIA) multilevel technique: a method to analyze the complete epoch of event-related potentials at single trial level.

In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on this assumption, we introduce a new concept which allows for flexible investigation of the whole epoch and does not primarily focus on peaks and their corresponding latencies. For each trial, the entire epoch is partitioned into event-related fixed-interval areas under the curve (ERFIAs). These ERFIAs, obtained at single trial level, act as dependent variables in a multilevel random regression analysis. The ERFIA multilevel method was tested in an existing ERP dataset of 85 healthy subjects, who underwent a rating paradigm of 150 painful and non-painful somatosensory electrical stimuli. We modeled the variability of each consecutive ERFIA with a set of predictor variables among which were stimulus intensity and stimulus number. Furthermore, we corrected for latency variations of the P2 (260 ms). With respect to known relationships between stimulus intensity, habituation, and pain-related somatosensory ERP, the ERFIA method generated highly comparable results to those of commonly used methods. Notably, effects on stimulus intensity and habituation were also observed in non-peak-related latency ranges. Further, cortical processing of actual stimulus intensity depended on the intensity of the previous stimulus, which may reflect pain-memory processing. In conclusion, the ERFIA multilevel method is a promising tool that can be used to study event-related cortical processing.