Unraveling the Left-Right Judgment Task in Chronic Low Back Pain: Insights Through Behavioral, Electrophysiological, Motor Imagery, and Bodily Disruption Perspectives.

Bodily disruptions have been consistently demonstrated in individuals with chronic low back pain. The performance on the left-right judgment task has been purposed as an indirect measure of the cortical proprioceptive representation of the body. It has been suggested to be dependent on implicit motor imagery, although the available evidence is conflicting. Hence, the aim of this case-control observational study was to examine the performance (accuracy and reaction times) and event-related potentials while performing the left-right judgment task for back and hand images in individuals with chronic low back pain versus healthy controls, along with its relationship with self-reported measurements and quantitative sensory testing. While self-reported data suggested bodily disruptions in the chronic low back pain sample, this was not supported by quantitative sensory testing. Although both groups displayed the same performance, our results suggested an increased attentional load on participants with chronic low back pain to achieve equal performance, measured by a higher N1 peak amplitude in occipital electrodes, especially when the effect of contextual images arises. The absence of differences in the reaction times for the left-right judgment task between both groups, along with inconsistencies in self-reported and quantitative sensory testing data, could question the involvement of implicit motor imagery in solving the task. In conclusion, our results suggest disrupted attentional processing in participants with chronic low back pain to solve the left-right judgment task. PERSPECTIVE: Although there are no differences in the performance of the left-right judgment task (hits, reaction times) between chronic low back pain patients and controls, the analysis of event-related potentials revealed that patients require a higher cognitive load, measured by N1 peak amplitude.

An Educational and Exercise Mobile Phone-Based Intervention to Elicit Electrophysiological Changes and to Improve Psychological Functioning in Adults With Nonspecific Chronic Low Back Pain (BackFit App): Nonrandomized Clinical Trial.

BACKGROUND: Concomitant psychological and cognitive impairments modulate nociceptive processing and contribute to chronic low back pain (CLBP) maintenance, poorly correlated with radiological findings. Clinical practice guidelines recommend self-management and multidisciplinary educational and exercise-based interventions. However, these recommendations are based on self-reported measurements, which lack evidence of related electrophysiological changes. Furthermore, current mobile health (mHealth) tools for self-management are of low quality and scarce evidence. Thus, it is necessary to increase knowledge on mHealth and electrophysiological changes elicited by current evidence-based interventions. OBJECTIVE: The aim of this study is to investigate changes elicited by a self-managed educational and exercise-based 4-week mHealth intervention (BackFit app) in electroencephalographic and electrocardiographic activity, pressure pain thresholds (PPTs), pain, disability, and psychological and cognitive functioning in CLBP versus the same intervention in a face-to-face modality. METHODS: A 2-arm parallel nonrandomized clinical trial was conducted at the University of the Balearic Islands (Palma, Spain). A total of 50 patients with nonspecific CLBP were assigned to a self-managed group (23/50, 46%; mean age 45.00, SD 9.13 years; 10/23, 43% men) or a face-to-face group (27/50, 54%; mean age 48.63, SD 7.54 years; 7/27, 26% men). The primary outcomes were electroencephalographic activity (at rest and during a modified version of the Eriksen flanker task) and heart rate variability (at rest), PPTs, and pressure pain intensity ratings. The secondary outcomes were pain, disability, psychological functioning (mood, anxiety, kinesiophobia, pain catastrophizing, and fear-avoidance beliefs), and cognitive performance (percentage of hits and reaction times). RESULTS: After the intervention, frequency analysis of electroencephalographic resting-state data showed increased beta-2 (16-23 Hz; 0.0020 vs 0.0024; P=.02) and beta-3 (23-30 Hz; 0.0013 vs 0.0018; P=.03) activity. In addition, source analyses revealed higher power density of beta (16-30 Hz) at the anterior cingulate cortex and alpha (8-12 Hz) at the postcentral gyrus and lower power density of delta (2-4 Hz) at the cuneus and precuneus. Both groups also improved depression (7.74 vs 5.15; P=.01), kinesiophobia (22.91 vs 20.87; P=.002), activity avoidance (14.49 vs 12.86; P<.001), helplessness (6.38 vs 4.74; P=.02), fear-avoidance beliefs (35 vs 29.11; P=.03), and avoidance of physical activity (12.07 vs 9.28; P=.01) scores, but there was an increase in the disability score (6.08 vs 7.5; P=.01). No significant differences between the groups or sessions were found in heart rate variability resting-state data, electroencephalographic data from the Eriksen flanker task, PPTs, subjective ratings, or cognitive performance. CONCLUSIONS: Both intervention modalities increased mainly beta activity at rest and improved psychological functioning. Given the limitations of our study, conclusions must be drawn carefully and further research will be needed. Nevertheless, to the best of our knowledge, this is the first study reporting electroencephalographic changes in patients with CLBP after an mHealth intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04576611; https://clinicaltrials.gov/ct2/show/NCT04576611.

EEG-heart rate connectivity changes after sensorimotor rhythm neurofeedback training: Ancillary study.

OBJECTIVES: Neurofeedback can induce long-term changes in brain functional connectivity, but its influence on the connectivity between different physiological systems is unknown. The present paper is an ancillary study of a previous paper that confirmed the effect of neurofeedback on brain connectivity associated with chronic pain. We analysed the influence of neurofeedback on the connectivity between the electroencephalograph (EEG) and heart rate (HR). METHODS: Seventeen patients diagnosed with fibromyalgia were divided into three groups: good sensorimotor rhythm (SMR) training responders (n = 4), bad SMR responders (n = 5) and fake training (SHAM, n = 8). Training consisted of six sessions in which participants learned to synchronize and desynchronize SMR power. Before the first training (pre-resting state) and sixth training (post-resting state) session, open-eye resting-state EEG and electrocardiograph signals were recorded. RESULTS: Good responders reduced pain ratings after SMR neurofeedback training. This improvement in fibromyalgia symptoms was associated with a reduction of the connectivity between the central area and HR, between central and frontal areas, within the central area itself, and between central and occipital areas. The sham group and poor responders experienced no changes in their fibromyalgia symptoms. CONCLUSIONS: Our results provide new evidence that neurofeedback is a promising tool that can be used to treat of chronic pain syndromes and to obtain a better understanding of the interactions between physiological networks. These findings are preliminary, but they may pave the way for future studies that are more methodologically robust. In addition, new research questions are raised: what is the role of the central-peripheral network in chronic pain and what is the effect of neurofeedback on this network.

Somatosensory Gating Is Modulated by Anodal Transcranial Direct Current Stimulation.

BACKGROUND: Anodal transcranial direct current stimulation (tDCS) of the somatosensory cortex causes cerebral hyperexcitability and a significant enhancement in pain thresholds and tactile spatial acuity. Sensory gating is a brain mechanism to suppress irrelevant incoming inputs, which is elicited by presenting pairs of identical stimuli (S1 and S2) within short time intervals between stimuli (e.g., 500 ms). OBJECTIVES/HYPOTHESIS: The present study addressed the question of whether tDCS could modulate the brain correlates of this inhibitory mechanism. METHODS: Forty-one healthy individuals aged 18-26 years participated in the study and were randomly assigned to tDCS (n = 21) or SHAM (n = 20). Somatosensory evoked potentials (SEP) elicited by S1 and S2 pneumatic stimuli (duration of 100 ms, ISI 550 ± 50 ms) and applied to the index finger of the dominant hand were recorded before and after tDCS. RESULTS: Before the intervention, the second tactile stimuli significantly attenuated the amplitudes of P50, N100, and the late positive complex (LPC, mean amplitude in the time window 150-350) compared to the first stimuli. This confirmed that sensory gating is a widespread brain inhibitory mechanism that can affect early- and middle-latency components of SEPs. Furthermore, our data revealed that this response attenuation or sensory gating (computed as S1 minus S2) was improved after tDCS for LPC, while no changes were found in participants who received SHAM. CONCLUSION: All these findings suggested that anodal tDCS might modulate brain excitability leading to an enhancement of inhibitory mechanisms elicited in response to repetitive somatosensory stimuli during late stages of information processing.

Anterior Cingulate Cortex Activity During Rest Is Related to Alterations in Pain Perception in Aging.

Alterations in the affective component of pain perception are related to the development of chronic pain and may contribute to the increased vulnerability to pain observed in aging. The present study analyzed age-related changes in resting-state brain activity and their possible relation to an increased pain perception in older adults. For this purpose, we compared EEG current source density and fMRI functional-connectivity at rest in older (n = 20, 66.21 ± 3.08 years) and younger adults (n = 21, 20.71 ± 2.30 years) and correlated those brain activity parameters with pain intensity and unpleasantness ratings elicited by painful stimulation. We found an age-related increase in beta2 and beta3 activity in temporal, frontal, and limbic areas, and a decrease in alpha activity in frontal areas. Moreover, older participants displayed increased functional connectivity in the anterior cingulate cortex (ACC) and the insula with precentral and postcentral gyrus. Finally, ACC beta3 activity was positively correlated with pain intensity and unpleasantness ratings in older, and ACC-precentral/postcentral gyrus connectivity was positively correlated with unpleasantness ratings in older and younger participants. These results reveal that ACC resting-state hyperactivity is a stable trait of brain aging and may underlie their characteristic altered pain perception.

Age-Related Changes in Pain Perception Are Associated With Altered Functional Connectivity During Resting State.

Aging affects pain experience and brain functioning. However, how aging leads to changes in pain perception and brain functional connectivity has not yet been completely understood. To investigate resting-state and pain perception changes in old and young participants, this study employed region of interest (ROI) to ROI resting-state functional connectivity (rsFC) analysis of imaging data by using regions implicated in sensory and affective dimensions of pain, descending pain modulation, and the default-mode networks (DMNs). Thirty-seven older (66.86 ± 4.04 years; 16 males) and 38 younger healthy participants (20.74 ± 4.15 years; 19 males) underwent 10 min' eyes-closed resting-state scanning. We examined the relationship between rsFC parameters with pressure pain thresholds. Older participants showed higher pain thresholds than younger. Regarding rsFC, older adults displayed increased connectivity of pain-related sensory brain regions in comparison to younger participants: increased rsFC between bilateral primary somatosensory area (SI) and anterior cingulate cortex (ACC), and between SI(L) and secondary somatosensory area (SII)-(R) and dorsolateral prefrontal cortex (PFC). Moreover, decreased connectivity in the older compared to the younger group was found among descending pain modulatory regions: between the amygdala(R) and bilateral insula(R), thalamus(R), ACC, and amygdala(L); between the amygdala(L) and insula(R) and bilateral thalamus; between ACC and bilateral insula, and between periaqueductal gray (PAG) and bilateral thalamus. Regarding the DMN, the posterior parietal cortex and lateral parietal (LP; R) were more strongly connected in the older group than in the younger group. Correlational analyses also showed that SI(L)-SII(R) rsFC was positively associated with pressure pain thresholds in older participants. In conclusion, these findings suggest a compensatory mechanism for the sensory changes that typically accompanies aging. Furthermore, older participants showed reduced functional connectivity between key nodes of the descending pain inhibitory pathway.

Self-Regulation of SMR Power Led to an Enhancement of Functional Connectivity of Somatomotor Cortices in Fibromyalgia Patients.

Neuroimaging studies have demonstrated that altered activity in somatosensory and motor cortices play a key role in pain chronification. Neurofeedback training of sensorimotor rhythm (SMR) is a tool which allow individuals to self-modulate their brain activity and to produce significant changes over somatomotor brain areas. Several studies have further shown that neurofeedback training may reduce pain and other pain-related symptoms in chronic pain patients. The goal of the present study was to analyze changes in SMR power and brain functional connectivity of the somatosensory and motor cortices elicited by neurofeedback task designed to both synchronize and desynchronize the SMR power over motor and somatosensory areas in fibromyalgia patients. Seventeen patients were randomly assigned to the SMR training (n = 9) or to a sham protocol (n = 8). All participants were trained during 6 sessions, and fMRI and EEG power elicited by synchronization and desynchronization trials were analyzed. In the SMR training group, four patients achieved the objective of SMR modulation in more than 70% of the trials from the second training session (good responders), while five patients performed the task at the chance level (bad responders). Good responders to the neurofeedback training significantly reduced pain and increased both SMR power modulation and functional connectivity of motor and somatosensory related areas during the last neurofeedback training session, whereas no changes in brain activity or pain were observed in bad responders or participants in the sham group. In addition, we observed that good responders were characterized by reduced impact of fibromyalgia and pain symptoms, as well as by increased levels of health-related quality of life during the pre-training sessions. In summary, the present study revealed that neurofeedback training of SMR elicited significant brain changes in somatomotor areas leading to a significant reduction of pain in fibromyalgia patients. In this sense, our research provide evidence that neurofeedback training is a promising tool for a better understanding of brain mechanisms involved in pain chronification.

Power Spectral Density and Functional Connectivity Changes due to a Sensorimotor Neurofeedback Training: A Preliminary Study.

Neurofeedback is a form of neuromodulation based on learning to modify some aspects of cortical activity. Sensorimotor rhythm (SMR) oscillation is one of the most used frequency bands in neurofeedback. Several studies have shown that subjects can learn to modulate SMR power to control output devices, but little is known about possible related changes in brain networks. The aim of this study was to investigate the enhanced performance and changes in EEG power spectral density at somatosensory cerebral areas due to a bidirectional modulation-based SMR neurofeedback training. Furthermore, we also analyzed the functional changes in somatosensory areas during resting state induced by the training as exploratory procedure. A six-session neurofeedback protocol based on learning to synchronize and desynchronize (modulate) the SMR was implemented. Moreover, half of the participants were enrolled in two functional magnetic resonance imaging resting-state sessions (before and after the training). At the end of the training, participants showed a successful performance enhancement, an increase in SMR power specific to somatosensory locations, and higher functional connectivity between areas associated with somatosensory activity in resting state. Our research increases the better understanding of the relation between EEG neuromodulation and functional changes and the use of SMR training in clinical practice.

Corrigendum: Inhibitory Control Impairment on Somatosensory Gating Due to Aging: An Event-Related Potential Study.

[This corrects the article DOI: 10.3389/fnhum.2018.00280.].

Inhibitory Control Impairment on Somatosensory Gating Due to Aging: An Event-Related Potential Study.

The capacity to suppress irrelevant incoming input, termed sensory gating, is one of the most investigated inhibitory processes associated with cognitive impairments due to aging. The aim of this study was to examine the influence of aging on sensory gating by using somatosensory event-related potentials (ERPs) elicited by repetitive non-painful tactile stimulation (paired-pulsed task). Somatosensory ERPs were recorded in 20 healthy young adults and 20 healthy older adults while they received two identical pneumatic stimuli (S1 and S2) of 100 ms duration with an inter-stimulus interval of 550 ± 50 ms on both forefingers. The difference between the somatosensory ERPs amplitude elicited by S1 and S2 was computed as a sensory gating measure. The amplitude and the latency of P50, N100 and late positive complex (LPC) were analyzed as well as the source generators of the gating effect. Reduced sensory gating was found in older individuals for N100 at frontal and centro-parietal electrodes and for LPC at fronto-central electrodes. Source localization analyses also revealed a reduced current density during gating effect in the older group in frontal areas in N100 and LPC. Moreover, older individuals showed delayed latencies in N100. No significant gating effect differences were found between groups in P50. These findings suggest an age-related slowing of processing speed and a reduced efficiency of inhibitory mechanisms in response to repetitive somatosensory information during stimulus evaluation, and a preservation of processing speed and inhibitory control during early stimulus coding in aging.

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats.

Limiting enzymes in the synthesis of brain monoamines seems to be susceptible to oxidative damage, one of the most important factors in aging. It has been suggested that the use of anti-oxidants can reduce the rate of free radical production related with aging and the associated damage. Therefore, this study aims to analyze the effects of the chronic treatments with the anti-oxidant α-tocopherol (vitamin E) on central monoamines (high-performance liquid chromatography [HPLC] analysis) mediating cognitive functions, as well as on the evaluation of memory and motor abilities in old rats measured by radial maze, Barnes maze, novel object recognition test, and rotarod test. Results show that α-tocopherol significantly increased in a dose- and/or time-dependent manner the synthesis rate and the levels of monoaminergic neurotransmitters (serotonin, dopamine, and noradrenaline) in the hippocampus and striatum, brain regions involved in memory processing and motor coordination. These positive neurochemical effects, largely due to an increased activity of the limiting enzymes in monoamines synthesis, tryptophan hydroxylase and tyrosine hydroxylase, were accompanied by an improvement in cognitive and motor abilities in old rats. Altogether these findings suggest that α-tocopherol exhibits neuroprotective actions in old rats; thus, diets with α-tocopherol might represent a promising strategy to mitigate or delay the cognitive and motor decline associate with aging and related-diseases.