EEG Theta-Beta Ratio Neurofeedback-training
Condition: Elevated EEG Theta/Beta Ratio
Study type: Interventional

Summary: 
      This study will investigate the effects of an EEG theta/beta ratio Neurofeedback training
      using a case series multiple baseline design. Twelve participants will be assigned to one of
      three different groups that have a different time of intervention onset, or include placebo
      sessions only. The investigators will examine whether the theta/beta ratio Neurofeedback
      training will reduce resting state theta/beta ratio. As a pilot-exploration for future
      studies, also performance on a cognitive interference task will be monitored to see if any
      improvement after NFT on cognitive performance might be a viable subject for future studies.
      All participants (healthy, but selected for above-median theta/beta ratio in previous studies
      in this lab) will start with three resting state EEG baseline sessions, the first participant
      group then continues with 14 theta/beta ratio Neurofeedback sessions, the second group
      continues with six extra baseline EEG measurements, followed by eight Neurofeedback training
      sessions while the third group will continue with 14 placebo training sessions only. EEG
      resting state theta/beta ratio and interference performance will be measured during every
      session.
    

Detailed description: 
      Background Resting state EEG measures can produce useful spectral indices of power in
      different frequency bands. One robust finding in attention-deficit/ hyperactivity disorder
      (ADHD) has been increased theta band power (typically 4-7 Hz) relative to beta band power
      (13-30 Hz) otherwise expressed as the 'theta beta ratio' (TBR; Barry, Clark & Johnstone,
      2003). TBR possibly reflects interactions between subcortical and prefrontal cortical areas
      in the brain (Schutter & Knyazev, 2012). A recent study from the Leiden University lab showed
      that increased TBR was related to less self-reported attentional control and correlated to a
      stronger decline in attentional control after stress-induction (Putman et al., 2014) which
      are core elements of cognitive performance anxiety (CPA); a phenomenon defined as when fears
      compromise an individual's capacity to execute a task. Given that theta/beta ratio might
      serve as a marker for PFC-mediated attentional control and vulnerability to the effects of
      CPA, the eventual goal of our research program is to test whether theta/beta ratio reduction
      might be effective in reducing symptoms of CPA. Neurofeedback training is a method to induce
      changes in EEG frequency power bands. Online feedback on people's EEG spectrum while asking
      to increase or decrease power in certain frequency bands can eventually lead to the ability
      to do this (Vernon, 2005). Application of a TBR Neurofeedback training with the aim to reduce
      TBR might be effective in reducing attentional dysfunction as in ADHD patients (Lofthouse et
      al., 2012) and might possibly increase resilience to deleterious effects of stress on
      cognition (Putman et al., 2014). The investigators would ultimately like to study effects of
      this training in individuals with elevated vulnerability for CPA; having a higher than
      average TBR. The primary goal of the current study is only to see if it is possible to change
      the EEG TBR signature in this population by means of our NFT protocol. Additionally, we would
      like to explore the effects on prefrontal mechanisms regulating attention to interfering
      distractors by administering a letter string interference task (Bishop, 2009) on fixed
      moments during the training. Data pertaining to this cognitive measure will only be used to
      inform design of future studies and any finding will be mentioned in publications explicitly
      as being exploratory (if at all) and not providing evidence to accept or reject any
      hypotheses about effects of our NFT protocol on cognitive performance. Our design will be
      different from the widely used randomized controlled trials design (RCT). RCT designs are
      generally considered to be superior to other methods in estimating an interventions true
      effect. However other designs such as case studies or well-matched comparison group - studies
      may provide information that is just as valuable in clinical intervention studies in the case
      that the intervention provides compelling evidence of its effect. The current study will
      serve as a first try-out whether we can reduce TBR using a Neurofeedback training for which
      an RCT design might unnecessarily cost a considerable lot of time and effort. We propose an
      alternative to the RCT design, namely using smaller groups of participants that start with
      EEG resting state measurements as a baseline and switch to real Neurofeedback training on
      different points in time; so called 'case series multiple baseline design'. Practical
      advantages of the multiple baseline design are that the design requires fewer participants
      and that participants act as their own controls. Visual inspection and single-case statistics
      will be used to determine the effectiveness of this Neurofeedback training by observing
      differences of TBR per group over time (see section 'Statistical analysis plan').

      Aims, research question and hypothesis The main aims of this study will be to evaluate the
      effects of a Neurofeedback training on reducing EEG theta/beta ratio in individuals having
      elevated baseline TBR. Furthermore, with a very second degree of importance, the
      investigators will test if a reduction in TBR increases cognitive performance on a response
      conflict task.

      The research questions will be; can a TBR Neurofeedback training in healthy (non-ADHD) people
      with elevated TBR reduce TBR and (very much secondary) will the training perhaps increase
      cognitive performance on a response conflict task? If so we might continue with further
      studies to assess NFT effects on cognitive performance in CPA in healthy people. It is
      expected that TBR will reduce after training onset. Also, it is expected that performance on
      the interference task will improve after participants have started with the TBR Neurofeedback
      training.

      Design The investigators will use a single blind case series multiple baseline design with a
      baseline varying prior to training onset. By randomizing 12 participants over three
      conditions of different training onset points in time, the investigators will use a variation
      in baseline which offers the possibility to differentiate between time effects of the
      Neurofeedback training. All participants will start with a three-session baseline phase which
      will include a session with questionnaires, interference task training (in order to quickly
      reach a learning effect ceiling to better be able to observe additional performance change
      after intervention) and a resting state EEG measurement followed by two other sessions of
      resting state EEG measurements and the interference task. Participants in group A will then
      continue with 14 sessions of TBR Neurofeedback training. Group B will receive six extra
      baseline EEG measurements before they continue with eight TBR Neurofeedback sessions. Group C
      on the other hand will only receive 14 placebo training sessions after the short baseline
      phase. Before every TBR Neurofeedbacktraining or placebo training, a four-minute EEG
      resting-state baseline measurement will be performed.

      The minimal number of real training sessions (eight) are necessary for making it possible to
      observe the onset of an effect of the Neurofeedback training, based on previous studies using
      a TBR Neurofeedback training (e.g. Studer et al., 2014; Doppelmayr & Weber, 2011; Leins et
      al., 2007; Gevensleben et al., 2009). Also, a higher number of training sessions is important
      to ensure that a possible delayed effect of the Neurofeedback training can still be observed.

      Procedure Before the first lab session, the participants will be stratified randomly assigned
      to one of the three groups. All participants will visit the lab 17 times. During the first
      visit, participants will fill in an informed consent, demographic information and
      questionnaires. They will continue with a training for the letter string interference task to
      avoid learning effects. At the end of the first visit, EEG resting state will be measured.
      During the second and third visit, participants will only receive a resting state EEG
      measurement and perform the letter string interference task. In the sessions after these
      baseline measurements, participants will receive a 4 minute EEG eyes-open resting state
      measurement, following either TBR Neurofeedback training or a placebo training depending on
      the participant group. After the Neurofeedback training, resting state measurement or placebo
      training, participants will always perform the letter string interference task. Sessions will
      be (almost) daily and approximately take between 50-60 minutes; except for the first
      questionnaires/interference training session which will take 90 minutes. The complete
      experiment will therefore take 17-19 hours per participant in 4-6 weeks.

      Materials and training Questionnaires The participants will complete demographic information
      and fill in the trait and state version of the State-Trait Anxiety Inventory (STAI-t, STAI-s;
      Spielberger, 1983; Van der Ploeg et al., 1981) adapted to only report about the past week
      before the first session, and the trait and state version of the Attentional Control Scale
      (ACS; Derryberry & Reed, 2002). The STAI-t assesses trait anxiety (range 20-80), STAI-s
      assesses the participant's current state of anxiety, and the ACS assesses attentional
      inhibition, attentional shift, and the capacity to flexibly generate new thoughts (range
      20-80). The internal consistency of these questionnaires is generally good. STAI- t, ACS-t
      and a demographic questionnaire will only be measured during the first session and during the
      last session (after the training). The STAI-s and ACS-s will be assessed on every session
      before the EEG measurement or training.

      Letter string interference task

      The Letter String interference task will be as in Bishop (2009) with the only difference that
      in this study the neutral trials will be left out as they have no informative value on
      cognitive interference.

      Neurofeedback theta/beta ratio training. The TBR Neurofeedback signal will be given by means
      of a NeXus-4 amplifier and recording system (Mindmedia, The Netherlands). One Ag/AgCl
      disposable electrode will be applied on the participant's scalp between locations Cz and FCz.
      For a high-quality and accurate EEG measurement, 16 extra in-cap electrodes (BioSemi, The
      Netherlands) will be added on locations F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, T7, TP7, T8, TP8,
      O1, Oz and O2) during every session. Each session will consist of a four-minute resting state
      measurement, followed by a 25 minute measurement/Neurofeedback training or placebo training.
      The thresholds will be set 20% above (beta) or below (theta) the participant's amplitude,
      calculated and adjusted automatically every 15 seconds. During the training, theta and beta
      activity will be visualized in separate bar graphs on the screen and participants will be
      instructed to "try to move down the theta activity and move up the beta activity below or
      above the threshold". No instructions about how to influence their activity will be given.
      When the EEG theta power goes below the threshold, and the beta power above its threshold
      simultaneously, the participant will be rewarded by the continuation of a video. If they fail
      to reach this point, the video will be paused.

      The placebo training will be a previously recorded Neurofeedback session of a participant in
      group A (receiving 14 real Neurofeedback sessions). Before the participants in group C
      (placebo trainings) start, they will be matched to a participant in group A, and receive the
      exact same (prerecorded) feedback per session of their matched participant. In this way,
      participants in the placebo training are then made to think that the video and EEG feedback
      is their own, however they are actually not able to influence the continuation of the video.

      Data analysis For interpreting the results, visual inspection will be primarily used to
      determine the effectiveness of the TBR Neurofeedback training. If TBR in group A reduces
      after the introduction of the real Neurofeedback training compared to no changes in group C,
      the experiment provides compelling evidence for the effectiveness of the Neurofeedback
      training. The effect will be even more strongly supported if we see a similar reduction after
      Neurofeedback training onset in group A and B (as in after an equal number of actual NFT
      sessions as in group A, regardless the longer duration of the baseline). These changes after
      onset in group A and group B are assumed to be absent in group C, where we expect no changes
      at all. The expected effect in group B can also be considered as a direct replication of the
      effect in group A. The idealized expected changes in TBR are depicted in Figure 3 (each
      individual line represents changes in TBR per group). These visual inspections serve as
      testing of the primary outcome measures.

      In addition to the primary test by visual inspection, secondary, we will perform statistical
      tests between the average TBR of group A and B together on an equal number of sessions after
      training onset compared to group C on the same number of sessions as group A (i.e. session 10
      for group A averaged with session 14 for group B compared to session 10 for group C). Also,
      we will calculate eight separate contrast scores of average TBR within group A of session 1
      minus session 17; session 2 minus session 16; session 3 minus session 15 etc. The same will
      be done for group B and C followed by a statistical comparison of the contrast scores of
      group A and B (taken together as one group) with the contrast scores of group C.

      Tertiary, only in the case that in group A there seems to be evidence of change in TBR at
      approximately the same session in time as per visual inspection,, we will test a direct
      replication of this effect in group B using a similar permutation testing method as Ter Kuile
      et al., (2009, see also Bulté and Onghena, 2008 ) The approximate time-point of TBR change in
      group A might serve to designate the per-session TBR data as either pre- or
      post-intervention.
    

Intervention name(s): Neurofeedback; Placebo Neurofeedback training
Intervention type(s): Other; Other
Intervention description(s): Neurofeedback theta/beta ratio training. See 'Neurofeedback theta/beta ratio training' in detailed study description.; The placebo training will be a previously recorded Neurofeedback session of a participant in group A
Other intervention name(s): theta/beta ratio neurofeedback
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Neurofeedback; theta/beta ratio; multiple baseline