Volitional limbic neuromodulation has a multifaceted clinical benefit in Fibromyalgia patients

43 Volitional neural modulation using neurofeedback has been indicated as a potential 44 treatment for chronic conditions that involve peripheral and central neural 45 dysregulation. Here we utilized neurofeedback in patients suffering from 46 Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion 47 dysregulation. These ancillary symptoms, which have an amplification effect on pain, 48 are known to be mediated by heightened limbic activity. In order to reliably probe 49 limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized 50 an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg- 51 EFP), that has been successfully validated in our lab in the context of volitional 52 neuromodulation. 53 We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down 55 modulation should improve chronic pain in patients suffering from Fibromyalgia, by 56 balancing disturbed indices for sleep and affect. We further expected that improved 57 clinical status would correspond to successful training as indicated by improved down 58 modulation of the Amygdala-EFP signal. 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 78 by the immediate improvements following training in objective sleep and subjective 79 affect measures. Our findings suggest that Amyg-EFP- neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG 83 based neuromodulation training in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a 85 delayed reduction in the target subjective symptom of chronic pain, far and beyond 86 the immediate placebo effect. This indirect approach to chronic pain management 87 reflects the necessary link between somatic and affective dysregulation that can be 88 successfully targeted using neurofeedback. We hypothesized that: (1) Fibromyalgia patients in the Real-NF group would exhibit greater down modulation of the Amyg-EFP signal than the control group. (2) Given that our training probe was limbic and not classically related to the core pain processing network (Apkarian et al., 2005), we expected that the Amyg-EFP-NF training would differentially improve ancillary symptoms related to homeostasis as demonstrated by sleep and affect impairments. Moreover, we expected these changes to be accompanied by improvement in chronic pain symptoms. (3) Individual differences in treatment outcome improvement would correspond to Real-NF success. placebo-controlled design with outcome measurements of homeostasis (sleep and affect) and pain, and accounting for measures of learning (good versus poor modulators), we show that Amyg-EFP-NF can serve as a scalable non-pharmacological, non–invasive treatment for individuals suffering from Fibromyalgia. By examining the therapeutic potential of limbic modulation in the specific case of Fibromyalgia, this study further serves to support the clinical potential of mechanism-driven fMRI driven EEG-NF approaches that target specific neural processes relevant to different disease states, thus promising to be a highly accessible therapeutic tool, both in medical settings as well as in the patient's home environment.