Brain-Computer Interface (BCI)-Based Feedback for Chronic Pain Management
Condition: Pain, Chronic
MeSH terms: Chronic Pain
Study type: Interventional

Summary: 
      The feasibility study proposed here will primarily examine the sensitivity of an
      electroencephalogram (EEG)-based Brain Computer Interface (BCI) in detecting significant
      differences in brain signals in patients with chronic low back pain (N=10), lower limb pain
      (N=10) and healthy controls (N=10) through perceived movements via a video and during actual
      movements. The BCI device has been approved for use in previous trials (e.g. NNI-IRB/07/001,
      DSRB Domain D/09/608, DSRB Domain D/10/072) and the safety and effectiveness of this
      non-invasive EEG-based BCI device validated through these trials. However, the validation has
      not been specific to its use in pain. Related to the primary objective of the study, we will
      develop and validate an adaptive and participant-specific pain detection and analysis program
      by exploring and identifying discriminative and robust patterns in spontaneous EEG from our
      study sample.

      For the secondary objective, we will develop and validate a BCI and computer based pain and
      attention diversion training system with interactive audio-visual feedbacks for Phase 2 of
      the study. These feedbacks will inform the user about the current brain activation level and
      attention level, and guide the user in learning to modulate the EEG characteristics and
      develop skills to manage attention to alleviate perceived fear-related pains. The BCI system
      captures EEG signals and decodes the underlying brain states in relation to cognition and
      fear-related pain perception. Such decoded brain states are then presented to the participant
      in visual or other form to guide the participant to learn to regulate the brain states
      towards better pain management. For example, the participant may over a few sessions learn to
      focus on the visual feedback while inhibiting the brain function activity in relation to
      fear-related pain perception. With practice, the user is encouraged to achieve brain activity
      modulation without external feedback so fear-related pain can be reduced in realistic
      situations.
    

Detailed description: 
      We hypothesize that, using appropriately designed system learning and computing techniques, a
      brain-computer interface (BCI) technology can detect specific brain wave patterns in patients
      with chronic low back pain or lower limb pain compared to healthy controls. Also, that BCI
      technology can detect specific brain wave patterns for fear avoidance behaviours in motor
      activities known to trigger pain in such chronic pain patients.

      This is a validation and feasibility study. We calculated sufficient funding to cover 10
      participants each with low back pain, lower limb pain, healthy controls and BCI training
      respectively. Participants will be screened and undergo a comprehensive assessment by the
      Rehabilitation Physician (RP) on the study team. The aim of the comprehensive assessment is
      to establish the safety and suitability of participants to be study subjects according to
      inclusion and exclusion criteria.To ensure a high level of compliance given the high
      frequency of visits of the subject during the study, it is important that motivated
      volunteers are chosen.

      Consent will be taken in an outpatient consultation room at the pain management clinic(PMC)
      at Tan Tock Seng Hospital, with full provision for privacy. PMC is where the study will be
      conducted. Informed consent will be taken at the convenience of the potential participant. A
      full explanation of the participant information sheet will be given and any questions
      answered.

      The study is conducted over 3 phases. Total span of study participation: 11-months.

      Phase 1: A total of 2 visits to the study site over 2 consecutive weeks is required. Each
      visit will take approximately 1 hour 15 minutes. The 1st session involves a visit to the
      doctor's office for a screening assessment-history taking, physical examination, and
      electronic notes review no different from the current standard pain consultation. Those found
      to be suitable and decide to take part, will be asked at the 2nd session to:

        1. Complete a digital set of self-report measures and a 6-minute walking test. These
           measures are completed at the start and end of the second session. The walking test will
           be conducted by a trained physiotherapist familiar with this measure.

        2. Participants then participate in two sets of non-invasive experiments one after another.
           The BCI system set-up comprising of a laptop connected to a brain signal recorder and a
           headset to record brain signals will be used. Sensors to measure sweat and pulse rate
           will also be used in the experiments. The brain signal recorder together with the
           sensors will be secured in a backpack and worn by participants during the experiments.

      Exp 1-participants watch 15 videos of people doing daily activities. Each video frame is
      approximately 1 min long. EEG signal patterns are recorded for each video frame.

      Exp 2-participants go through a series of 15 physical movements as guided by the
      physiotherapist. Participants are required to complete 15 repetitions each, within 1 min. EEG
      signal patterns are recorded for each movement. Two buzzers (labelled "lesser pain" and "more
      pain") are available for participants to press accordingly should they experience 'lesser' or
      'more' pain at any point during the experiment. If 'more' pain is experienced, the
      physiotherapist will assess the participant's condition and the participant will have a
      choice to either (1) continue the experiment at a lower intensity or (2) stop the experiment.

      Phase 2: Approximately 6 months after participants' participation in Phase 1 and span a
      period of 7 weeks. If selected to complete Phase 2, participants will undergo 18 sessions (3
      sessions/week) of brain training over a period of 6 consecutive weeks. Sessions are conducted
      on alternate days in the week with each session lasting approximately 1 hour. The same system
      set-up used in Phase 1 is used in each training session.

      At the start of the first session in week 1, and immediately after completing the last
      training session in Week 6 participants will also complete the same set of self-report
      questionnaires and the 6-minute walking test (as assessed in Phase 1). At week 7 (1 week post
      training) participants will complete the same full set of measures as set out in the second
      session of Phase 1.

      Phase 3: A total of 2 visits to the study site is required. Each visit will take
      approximately 1 hour 15 minutes. These 2 visits will be scheduled approximately 8.5 mths and
      10.5 mths after completing Phase 1. Both visit sessions involve a repeat of the full set of
      measures that participants completed at the 2nd session in Phase 1.

      Potential Risks

        1. The potential risks to participants are minimal as none of the measures and components
           of the system are invasive. There are currently no known safety issues with the headset
           and sensors. However participants will be kept informed of any new findings.

        2. Participants may experience temporary exertion related discomfort in the main muscle
           groups that are used in the physiotherapy guided movement experiment (Experiment 2)
           although the were designed to fit within participants' abilities. Participants will be
           advised to contact the Principal Investigator (PI) should the muscular discomfort
           persist for more than 24 hours.

        3. If participants are screened positive for depression at any point on the study, the PI
           who is a trained psychologist will screen them for active depression and where
           appropriate refer to the RP for further treatment recommendations. In this case, the
           participant will be excluded or withdrawn from the study.

        4. Due to the potential of the videos and the guided movements to elicit fear of pain,
           participants may experience some increase in anxiety and slight worsening of usual
           pains. Experiment 2 is performed under close supervision of the physiotherapist to
           prevent any possible strain caused by incorrect movements. If participants experience
           'more' pain, the physiotherapist will assess their condition and participants will have
           a choice to either (1) continue the experiment at a lower intensity or (2) stop the
           experiment.

           In the event that participants experience anxiety from participating on any of the
           experiments, the PI will assess their symptoms of anxiety and be able to administer
           appropriate intervention onsite as necessary at no cost. If further treatment is
           required, participants stop the experiment, get re-assessed by the RP and appropriate
           referrals will be made for treatment follow-up.

        5. As no other medication except simple analgesics such as Paracetamol,
           Paracetamol/Orphenadrine, Non-steroidal anti-inflammatory drugs or Tramadol to treat
           pain can be taken while participating on the study, there is a possibility pain may be
           exacerbated and their condition may worsen. If this occurs, the RP will re-assess their
           condition and make appropriate treatment recommendations.

        6. If participants pain condition is exacerbated at any point during the course of the
           study for reasons not indicated in points 1-4 above, they will be referred to the RP on
           the study team for an assessment who will then make appropriate treatment
           recommendations.

        7. if participants develop significant symptoms because of study participation which
           warrants medical intervention, a subsidized medical consult and follow-up treatment will
           be at their own costs. The RP on the study team will facilitate a fast tracked
           appointment at PMC within 2 weeks.

           Study Withdrawal: (a) Participants may withdraw voluntarily from participation in the
           study at any time. Participants may also withdraw voluntarily from receiving the study
           intervention for any reason. If voluntary withdrawal occurs, the participant will not be
           asked to continue scheduled evaluations and their involvement in the study will cease.

           (b) Any participant will be withdrawn from further participation on the study if a
           serious adverse event classified as having a reasonable causal relationship to the study
           occurs. In this case the participant will be given appropriate medical care until the
           symptoms resolve or the condition becomes stable. The participant will not be asked to
           continue scheduled evaluations and their involvement in the study will cease.

           (c) All participants will be withdrawn if there is study closure due to Domain Specific
           Review Board (DSRB) review. Participants who drop out of the study will not be replaced.

           (d) Any participant can be withdrawn from further participation on the study if the
           study team deem it is the best interest of the participant. This can also happen when
           the participant does not follow instructions required to complete the study adequately,
           or develops other medical problems during the study period.

           Specific Restrictions / Requirements:

           (a) Standard over the counter pregnancy testing kits will be used for the purposes of
           determining if a female of childbearing age is pregnant. (b) All forms of contraception
           are allowed during the entire duration of the study (c) Participants are limited to only
           taking simple analgesics such as Paracetamol, Paracetamol/Orphenadrine, Non-steroidal
           anti-inflammatory drugs (NSAIDs) or Tramadol while participating in the study (d) All
           medications (prescription and over the counter), vitamin and mineral supplements, and /
           or herbs taken by the participant will be documented.

           Data analysis: Self-report outcome measures and data from the walking test will be
           analysed via the Statistical Package for the Social Sciences (SPSS) package utilizing
           t-tests to measure group differences and pearson bivariate correlations to measure
           potential relationships between outcome measures and responses made on Exp 1 (video
           condition) and Exp 2 (physiotherapy guided movement condition). EEG patterns will be
           analysed via feature analysis in association with clinical signals and user
           states/condition including physiological measures of skin conductance and pulse rate.

           Data Storage: 1. All hardcopy data, will be stored in designated locked cabinet(s) that
           are accessible to authorized study personnel only. 2. All electronic data, they will be
           stored on in a secured computer that is password-protected. The databases will not
           contain participant identifiers and the data linking participant identifiers and the
           participant identification codes will be stored separately including those using
           portable media (e.g. CD, USB drives etc.).

           Data Access: 1. All study team members will have access to the research data which has
           password protection. 2. Data will not be released and shared with individuals or
           entities outside the institution. 3. Data will be destroyed after it has been stored for
           6 years or minimum duration of retention period as specific by our institutional policy,
           whichever that is longer.

           Data Monitoring: 1. Safety data will be monitored at every visit with participants asked
           to report adverse events since the last visit. 2.There are no anticipated adverse events
           or complications expected. However reported adverse events if any, will be fully
           recorded, graded in terms of severity, and classified as either not related to the
           study, or having a reasonable causal relationship to the study. 3. The PI will be
           responsible for reporting all adverse events to DSRB. If excess risk to the
           participant/s is observed, or a statistically significant benefit is observed, the study
           is stopped early and the patient informed of the results. Futility is not used as a
           stopping criteria as this is a feasibility trial design of which there is limited data,
           and of a small sample size. The final study results are needed to proof the study
           concept here. 4. The PI will be responsible for the dissemination of any data and safety
           information to the study site. Communication will be conducted weekly via secure e-mail
           to the study team during active phase of the study in Phase 1, 2 and 3. A monthly
           face-to-face meetings and where necessary ad hoc meetings during the period of the
           study.
    

Intervention name(s): EEG-based BCI analysis of fear avoidance
Intervention type(s): Device
Intervention description(s): Scalp EEG signals that are acquired and recorded from experiment 1 and 2 are analysed for healthy controls, participants with low back pain and participants with lower limb pain. Comparisons of signal patterns are made between groups. Assuming unique signal patterns are obtained for each groups, these signals are further analysed and used to develop a feedback brain training system to better manage pain and ideally reduce fear-avoidant behaviors towards pain.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Brain Computer Interface; Electroencephalogram (EEG); Chronic Pain