Volitional limbic neuromodulation has a multifaceted clinical benefit in Fibromyalgia patients

Publication date: Available online 5 November 2018

Source: NeuroImage

Author(s): Noam Goldway, Jacob Ablin, Omer Lubin, Yoav Zamir, Jackob Nimrod Keynan, Ayelet Or-Borichev, Marc Cavazza, Fred Charles, Nathan Intrator, Silviu Brill, Eti Ben-Simon, Haggai Sharon, Talma Hendler

Abstract

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplification effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation.

We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation should improve chronic pain in patients suffering from Fibromyalgia, by balancing disturbed indices for sleep and affect. We further expected that improved clinical status would correspond to successful training as indicated by improved down modulation of the Amygdala-EFP signal.

Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions and placebo of sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the Real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep Indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion.

REM latency and objective sleep quality index were robustly improved following the treatment course only in the Real-neurofeedback group (both time × group p < 0.05) and to a greater extent among good modulators (both time*sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the treatment. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the Real-neurofeedback group (both time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures.

Our findings suggest that Amyg-EFP- neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation training in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the necessary link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.

Graphical abstract

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