Brain-computer interface relieves chronic chemotherapy-induced peripheral neuropathy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) includes negative sensations that remain a major chronic problem for cancer survivors. Previous research demonstrated that neurofeedback (a closed-loop brain-computer interface [BCI]) was effective at treating CIPN versus a waitlist control (WLC). The authors' a priori hypothesis was that BCI would be superior to placebo feedback (placebo control [PLC]) and to WLC in alleviating CIPN and that changes in brain activity would predict symptom report. METHODS: Randomization to one of three conditions occurred between November 2014 and November 2018. Breast cancer survivors no longer in treatment were assessed at baseline, at the end of 20 treatment sessions, and 1 month later. Auditory and visual rewards were given over 20 sessions based on each patient's ability to modify their own electroencephalographic signals. The Pain Quality Assessment Scale (PQAS) at the end of treatment was the primary outcome, and changes in electroencephalographic signals and 1-month data also were examined. RESULTS: The BCI and PLC groups reported significant symptom reduction. The BCI group demonstrated larger effect size differences from the WLC group than the PLC group (mean change score: BCI vs. WLC, -2.60 vs. 0.38; 95% confidence interval, -3.67, -1.46 [p = .000; effect size, 1.07]; PLC, -2.26; 95% confidence interval, -3.33, -1.19 [p = .001 vs. WLC; effect size, 0.9]). At 1 month, symptoms continued to improve only for the BCI group. Targeted brain changes at the end of treatment predicted symptoms at 1 month for the BCI group only. CONCLUSIONS: BCI is a promising treatment for CIPN and may have a longer lasting effect than placebo (nonspecific BCI), which is an important consideration for long-term symptom relief. Although scientifically interesting, the ability to separate real from placebo treatment may not be as important as understanding the placebo effects differently from effects of the intervention. PLAIN LANGUAGE SUMMARY: Chemotherapy-induced nerve pain (neuropathy) can be disabling for cancer survivors; however, the way symptoms are felt depends on how the brain interprets the signals from nerves in the body. We determined that the perception of neuropathy can be changed by working directly with the brain. Survivors in our trial played 20 sessions of a type of video game that was designed to change the way the brain processed sensation and movement. In this, our second trial, we again observed significant improvement in symptoms that lasted after the treatment was complete.

The Long-Term Impact of Neurofeedback on Symptom Burden and Interference in Patients With Chronic Chemotherapy-Induced Neuropathy: Analysis of a Randomized Controlled Trial.

CONTEXT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment and may adversely affect quality of life (QOL) for years. OBJECTIVES: We explored the long-term effects of electroencephalographic neurofeedback (NFB) as a treatment for CIPN and other aspects of QOL. METHODS: Seventy-one cancer survivors (mean age 62.5; 87% females) with CIPN were randomized to NFB or to a waitlist control (WLC) group. The NFB group underwent 20 sessions of NFB where rewards were given for voluntary changes in electroencephalography. Measurements of pain, cancer-related symptoms, QOL, sleep, and fatigue were obtained at baseline, end of treatment, and one and four months later. RESULTS: Seventy one participants enrolled in the study. At the end of treatment, 30 in the NFB group and 32 in the WLC group completed assessments; at four months, 23 in the NFB group and 28 in the WLC completed assessments. Linear mixed model analysis revealed significant group × time interaction for pain severity. A general linear model determined that the NFB group had greater improvements in worst pain (primary outcome) and other symptoms such as numbness, cancer-related symptom severity, symptom interference, physical functioning, general health, and fatigue compared with the WLC group at the end of treatment and four months (all P < 0.05). Effect sizes were moderate or large for most measures. CONCLUSION: NFB appears to result in long-term reduction in multiple CIPN symptoms and improved postchemotherapy QOL and fatigue.

Randomized controlled trial of neurofeedback on chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors. METHODS: This was a randomized controlled trial with survivors assigned to an NFB group or a wait-list control (WLC) group. The NFB group underwent 20 sessions of NFB, in which visual and auditory rewards were given for voluntary changes in EEGs. The Brief Pain Inventory (BPI) worst-pain item was the primary outcome. The BPI, the Pain Quality Assessment Scale, and EEGs were collected before NFB and again after treatment. Outcomes were assessed with general linear modeling. RESULTS: Cancer survivors with CIPN (average duration of symptoms, 25.3 mo), who were mostly female and had a mean age of 62.5 years, were recruited between April 2011 and September 2014. One hundred percent of the participants starting the NFB program completed it (30 in the NFB group and 32 in the WLC group). The NFB group demonstrated greater improvement than the controls on the BPI worst-pain item (mean change score, -2.43 [95% confidence interval, -3.58 to -1.28] vs 0.09 [95% confidence interval, -0.72 to -0.90]; P =·.001; effect size, 0.83). CONCLUSIONS: NFB appears to be effective at reducing CIPN symptoms. There was evidence of neurological changes in the cortical location and in the bandwidth targeted by the intervention, and changes in EEG activity were predictive of symptom reduction. Cancer 2017;123:1989-1997. © 2017 American Cancer Society.

The Microbiome, Gut-Brain-Axis, and Implications for Brain Health.

As Antonio Damasio highlighted back in 1994, Descartes' division of mind and body slowed the full realization of the connectedness of the brain and the body by centuries. The simple fact that homeostasis in the brain was fully interconnected with the body has eluded researchers and clinicians even after the connection was well established. Recent studies reporting the central role in dysfunction of mental systems as a result of inflammation in the gut and the autonomic nervous system (ANS) was yet one more reminder that the entire system is connected and interdependent. Central to this discovery and its application to mental function has been the growing field of study of the microbiome. This article is an attempt to situate those who are active in the variety of ways and means of treating the brain in the essential role that is likely being played by a vast community of bacteria living in the bowels of the human being and influencing all of the higher and most "sophisticated" aspects of human interchange and thought. It is the authors hope that this brief introduction will remind and inform researchers and clinicians that the organism is more interconnected and more complex than we have tended to think and that disorders of the mind are likely also, often disorders of the gut.

Neuromodulation of cancer pain.

Managing cancer-related chronic pain is challenging to health care professionals as well as cancer patients and survivors. The management of cancer-related pain has largely consisted of pharmacological treatments, which has caused researchers to focus on neurotransmitter activity as a mediator of patients' perception of pain rather than the electrical activity during neurobiological processes of cancer-related pain. Consequently, brain-based pain treatment has focused mainly on neurotransmitters and not electrical neuromodulation. Neuroimaging research has revealed that brain activity is associated with patients' perceptions of symptoms across various diagnoses. The brain modulates internally generated neural activity and adjusts perceptions according to sensory input from the peripheral nervous system. Cancer-related pain may result not only from changes in the peripheral nervous system but also from changes in cortical activity over time. Thus, cortical reorganization by way of the brain's natural, plastic ability (neuroplasticity) may be used to manage pain symptoms. Physical and psychological distress could be modulated by giving patients tools to regulate neural activity in symptom-specific regions of interest. Initial research in nononcology populations suggests that encouraging neuroplasticity through a learning paradigm can be a useful technique to help treat chronic pain. Here we review evidence that indicates a measurable link between brain activity and patient-reported psychological and physical distress. We also summarize findings regarding both the neuroelectrical and neuroanatomical experience of symptoms, review research examining the mechanisms of the brain's ability to modify its own activity, and propose a brain-computer interface as a learning paradigm to augment neuroplasticity for pain management.