Increasing Sensori-Motor Rhythm Activity by EEG-Neurofeedback to Reduce the Impact of Pain on Daily Functioning
Condition: Chronic Pain Syndrome; Peripheral Neuropathic Pain
MeSH terms: Neuralgia; Chronic Pain
Study type: Interventional

Summary: 
      Background: Chronic neuropathic pain associated with peripheral neuropathies cannot be
      attributed solely to lesions of peripheral sensory axons and likely involves alteration in
      the processing of nociceptive information in the central nervous system in most patients. Few
      data are available regarding EEG correlates of chronic neuropathic pain. The fact is that
      effective cortical neuromodulation strategies to treat neuropathic pain target the precentral
      cortical region, i.e. a cortical area corresponding to the motor cortex. It is not known how
      these strategies might modulate brain rhythms in the central cortical region, but it can be
      speculated that sensorimotor rhythms (SMRs) are modified. Another potent way of modulating
      cortical rhythms is to use EEG-based neurofeedback (NFB). Rare studies previously aimed at
      relieving neuropathic pain using EEG-NFB training.

      Methods/Design: The objective of this single-centre, single-blinded, randomized controlled
      pilot study is to assess the value of an EEG-NFB procedure to relieve chronic neuropathic
      pain in patients with painful peripheral neuropathy. A series of 32 patients will be randomly
      assigned to one of the two following EEG-NFB protocols, aimed at increasing either the
      low-β(SMR)/high-β ratio (n=16) or the α(μ)/θ ratio (n=16) at central (rolandic) cortical
      level. Various clinical outcome measures will be collected before and one week after 12
      EEG-NFB sessions performed over 4 weeks. Resting-state EEG will also be recorded immediately
      before and after each NFB session. The primary endpoint will be the change in the impact of
      pain on patient&#39;s daily functioning, as assessed on the Interference Scale of the short
      form of the Brief Pain Inventory.

      Discussion: The value of EEG-NFB procedures to relieve neuropathic pain has been rarely
      studied. This pilot study will attempt to show the value of endogenous modulation of brain
      rhythms in the central (rolandic) region in the frequency band corresponding to the frequency
      of stimulation currently used by therapeutic motor cortex stimulation. In the case of
      significant clinical benefit produced by the low-β(SMR)/high-β ratio increasing strategy,
      this work could pave the way for using EEG-NFB training within the armamentarium of
      neuropathic pain therapy.
    

Detailed description: 
      1.1 - Description of the research proceedings and study design This is a single-centre,
      single-blinded, randomized controlled pilot study, in which 32 patients, aged between 18 and
      80 years, suffering from painful peripheral neuropathy (DN4 and NRS pain scores ≥4/10), will
      be randomly assigned to one of the two following EEG-NFB protocols, aimed at increasing
      either the SMR/high-β ratio (n=16) or the μ/θ ratio (n=16) at central (rolandic) cortical
      level in a 1:1 allocation ratio, stratified by age and gender. The group allocation of the
      patients will be performed by one investigator not involved in the EEG-NFB task or clinical
      assessment. Patients will be recruited in the Clinical Neurophysiology department of the
      Henri Mondor University Hospital, Créteil, France, where the research will take place.

      1.2 - Screening and inclusion visits During a routine medical visit, the study will be
      explained and proposed to the eligible patients and a letter of information about the
      protocol will be given to them. After a delay of reflection of at least a week, patients who
      agree to perform this research will be convened for an inclusion visit. After checking the
      inclusion/exclusion criteria, the informed consent form will be completed and signed by the
      participant and duly countersigned by the investigator.

      During this visit, clinical assessment based on the fulfillment of different scales and
      questionnaires will be performed.

      At the end of the inclusion visit, the patient will be randomized to either SMR/high-β or μ/θ
      training and the first EEG-NFB session will be performed.

      1.3 - NFB trial The trial phase will consist of 12 EEG-NFB sessions over 4 weeks (on 3
      consecutive days for 4 weeks). Each NFB session will last about 20 minutes, starting and
      ending with a recording of 2 minutes of resting-state EEG with eyes closed to investigate the
      impact of NFB on raw EEG. The NFB procedure will consist of 10 blocks of 75-second training
      separated by 15-second resting interval.

      1.4 - Final visit and follow-up A visit will take place at the end of the trial, 7 days after
      the last NFB session. During this visit, subjects will be administered almost the same
      clinical evaluation that they received at the inclusion visit.

      For the responders, defined as a reduction ≥30% of the 7-item Interference BPI score after
      the EEG-NFB procedure, an attempt to perform a transfer task will be proposed to the patient.
      From data collected during a semi-structured interview by the investigator on the strategy
      used by the patient to "succeed the game" during the NFB session, the mental process that the
      patient will have to use in the transfer task will be defined between the investigator and
      the patient. The purpose of the transfer task is to allow generalization of EEG-NFB benefit
      in real life conditions by realizing an NFB-like paradigm in which patients are invited to
      engage in the same cognitive strategies as for NFB but without presentation of the feedback
      signal.

      The patient will have to perform the transfer task for 20 minutes every morning for three
      weeks. At the end of the third week, the investigator will make a phone call to the patient
      to record the 7-item Interference BPI score.

      Study plan and measures:

      Inclusion visit: Inclusion/exclusion criteria; Signed informed consent; DN4 questionnaire;
      Randomization; Baseline assessment (BFI-fr, FMI-fr, BIS-fr, CSI, Exp-LoC-Q); Primary clinical
      outcome measures: BPI; Other clinical outcome measures (NRS, VRS, NPSI, PCS, HAD, TMT, FSS,
      LSEQ) 10 EEG-NFB sessions (4 weeks): Resting-state EEG recording; EEG-NFB procedure

      1 week after the last EEG-NFB session: Primary clinical outcome measures: BPI; Other clinical
      outcome measures (NRS, VRS, NPSI, PCS, HAD, TMT, FSS, LSEQ); Analgesic response, PGIC, Side
      effects After 3 weeks of transfer task (for responders to EEG-NFB): Primary clinical outcome
      measures: BPI
    

Intervention name(s): EEG-based neurofeedback for brain activity modulation
Intervention type(s): Other
Intervention description(s): NFB is a type of biofeedback technique for self-modulating brain activities by means of a learning task performed with ongoing sensory (usually visual) feedback to real-time acquisition of either brain imaging or electroencephalographic (EEG) signal, which serves as a biomarker of brain activity
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: EEG; neurofeedback; neuropathic pain; peripheral neuropathy; sensorimotor rhythm; treatment