EEG Theta-Beta Ratio Neurofeedback-training Using a Multiple Baseline Design

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.