Stimulus Presentation at Specific Neuronal Oscillatory Phases Experimentally Controlled with tACS: Implementation and Applications

In recent years it has become increasingly clear that both the power and phase of oscillatory brain activity can influence the processing and perception of sensory stimuli. Transcranial alternating current stimulation (tACS) can phase-align and amplify endogenous brain oscillations and has often been used to control and thereby study oscillatory power. Causal investigation of oscillatory phase is more difficult, as it requires precise real-time temporal control over both oscillatory phase and sensory stimulation. Here, we present hardware and software solutions allowing temporally precise presentation of sensory stimuli during tACS at desired tACS phases, enabling causal investigations of oscillatory phase. We developed freely available and easy to use software, which can be coupled with standard commercially available hardware to allow flexible and multi-modal stimulus presentation (visual, auditory, magnetic stimuli, etc.) at pre-determined tACS-phases, opening up a range of new research opportunities. We validate that stimulus presentation at tACS phase in our setup is accurate to the sub-millisecond level with high inter-trial consistency. Conventional methods investigating the role of oscillatory phase such as magneto-/electroencephalography can only provide correlational evidence. Using brain stimulation with the described methodology enables investigations of the causal role of oscillatory phase. This setup turns oscillatory phase into an independent variable, allowing innovative and systematic studies of its functional impact on perception and cognition

Neurofeedback As a Treatment for Major Depressive Disorder - A Pilot Study

BACKGROUND: There is growing interest in neurofeedback as a treatment for major depressive disorder. Reduction of asymmetry of alpha-activity between left and right prefrontal areas with neurofeedback has been postulated as effective in earlier studies. Unfortunately, methodological shortcomings limit conclusions that can be drawn from these studies. In a pilot-study, we investigated the effectiveness of reduction of asymmetry of alpha-activity with neurofeedback in depressed participants with the use of a stringent methodological approach. METHODS: Nine participants meeting DSM-IV criteria for major depressive disorder were treated with a maximum of 30 neurofeedback-sessions, aimed at reducing asymmetry of alpha-activity, over a 10-week period. No changes in the use of antidepressants were allowed 6 weeks before and during the intervention. Changes in depressive symptomatology were assessed with the Quick Inventory of Depressive Symptoms, self-report version. RESULTS: We observed response in 1 and remission in 4 out of a total of 9 participants. The effectiveness appeared largest in female participants. The mean asymmetry of alpha-activity decreased significantly over sessions in a quadratic fashion. This decrease was associated with clinical response. CONCLUSIONS: This pilot study suggests that neurofeedback aimed at a reduction of frontal asymmetry of alpha-activity may be effective as a treatment for depression. However, this was an open label pilot study. Non-specific effects of the procedure and/or a beneficial natural course may have confounded the results. Randomized controlled trials will have to establish the efficacy of neurofeedback for depression. TRIAL REGISTRATION: Nederlands Trial Register NTR1629

Validation of a neurofeedback paradigm:Manipulating frontal EEG alpha-activity and its impact on mood

It is claimed that neurofeedback (NF) is an effective treatment for a variety of psychiatric disorders. NF, within an operant conditioning framework, helps individuals to regulate cortical electroencephalographic (EEG) activity while receiving feedback from a visual or acoustic signal. For example, changing asymmetry between left and right frontal brain alpha activity by NF, is claimed to be an efficacious treatment for major depressive disorder. However, the specificity of this intervention in occasioning electrophysiological changes at target locations and target wave-frequencies, and its relation to changes in mood, has not been established. During a single session of NF, it was tested if the balance between left and right frontal alpha-activity could be changed, regardless of direction, in 40 healthy females. Furthermore, we investigated whether this intervention was electrophysiologically specific and if it was associated with changes in mood. Participants were able to decrease or increase frontal alpha-asymmetry during the intervention. However, no changes in mood were observed. Changes in EEG activity were specific in terms of location and wave-frequency

Alpha asymmetry during the NF sessions.

<p>**p<.05, ***p<.001.</p

Demograpic and clinical characteristics of participants.

<p>Note. QIDS- SR₁₆  =  Quick Inventory of Depressive Symptoms self-report version <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091837#pone.0091837-Rush1" target="_blank">[24]</a>.</p

CONSORT flow chart

<p>CONSORT flow chart</p

Stimulus Presentation at Specific Neuronal Oscillatory Phases Experimentally Controlled with tACS: Implementation and Applications Stimulus Presentation at Specific Neuronal Oscillatory Phases Experimentally Controlled with tACS: Implementation and Applic

In recent years, it has become increasingly clear that both the power and phase of oscillatory brain activity can influence the processing and perception of sensory stimuli. Transcranial alternating current stimulation (tACS) can phase-align and amplify endogenous brain oscillations and has often been used to control and thereby study oscillatory power. Causal investigation of oscillatory phase is more difficult, as it requires precise real-time temporal control over both oscillatory phase and sensory stimulation. Here, we present hardware and software solutions allowing temporally precise presentation of sensory stimuli during tACS at desired tACS phases, enabling causal investigations of oscillatory phase. We developed freely available and easy to use software, which can be coupled with standard commercially available hardware to allow flexible and multi-modal stimulus presentation (visual, auditory, magnetic stimuli, etc.) at pre-determined tACS-phases, opening up a range of new research opportunities. We validate that stimulus presentation at tACS phase in our setup is accurate to the sub-millisecond level with high inter-trial consistency. Conventional methods investigating the role of oscillatory phase such as magneto-/electroencephalography can only provide correlational evidence. Using brain stimulation with the described methodology enables investigations of the causal role of oscillatory phase. This setup turns oscillatory phase into an independent variable, allowing innovative, and systematic studies of its functional impact on perception and cognition