A Real-Time Phase-Locking System for Non-invasive Brain Stimulation

Abstract

Non-invasive brain stimulation techniques are entering widespread use for the investigation and treatment of a range of neurological and neuropsychiatric disorders. However, most current techniques are ‘open-loop’, without feedback from target brain region activity; this limitation could contribute to heterogeneous effects seen for nominally ‘inhibitory’ and ‘excitatory’ protocols across individuals. More potent and consistent effects may ensue from closed-loop and, in particular, phase-locked brain stimulation. In this work, a closed-loop brain stimulation system is introduced that can analyze EEG data in real-time, provide a forecast of the phase of an underlying brain rhythm of interest, and control pulsed transcranial electromagnetic stimulation to deliver pulses at a specific phase of the target frequency band. The technique was implemented using readily available equipment such as a basic EEG system, a low-cost Arduino board and MATLAB scripts. The phase-locked brain stimulation method was tested in 5 healthy volunteers and its phase-locking performance evaluated at 0, 90, 180, and 270 degree phases in theta and alpha frequency bands. On average phase locking values of 0.55° ± 0.11° and 0.52° ± 0.14° and error angles of 11° ± 11° and 3.3° ± 18° were achieved for theta and alpha stimulation, respectively. Despite the low-cost hardware implementation, signal processing time generated a phase delay of only 3.8° for theta and 57° for alpha stimulation, both readily accommodated in the pulse trigger algorithm. This work lays the methodological steps for achieving phase-locked brain stimulation for brief-pulse transcranial electrical stimulation (tES) and repetitive transcranial magnetic stimulation (rTMS), facilitating further research on the effect of stimulation phase for these techniques.

Transient Amplitude Modulation of Alpha-Band Oscillations by Short-Time Intermittent Closed-Loop tACS

“…By studying the immediate after-effects in intervals between periods of stimulation without artifacts, such studies may contribute towards exploring related online effects and enhance the understanding of tACS effects and mechanisms in general. One prominent recent study with phase-locked closed-loop stimulation was presented by Mansouri et al ( 2018 ). By using intermittent stimulation with very short (5 ms) square-wave pulses and an artifact removal procedure using a spline interpolation (Waddell et al, 2009 ), they were able to extract the artifact-free EEG signal and thus control for the actual phase locking of delivered stimulation and ongoing oscillation in alpha and theta bands.…”

Considerations for Pairing Cognitive Behavioral Therapies and Non-invasive Brain Stimulation: Ignore at Your Own Risk

“…Animal models may provide insights into how circuit engagement is influenced by biological therapeutics (e.g., stimulation, medication), behavioral training, and potential moderators (e.g., genetics, learning history, development, sex/hormonal status), as well as highlight individual differences to leverage and personalize CBT+NIBS. We should also consider strategies to time-lock circuit-based measurement with methods that quantify human behavior or targeted neural activation during CBT procedures in an effort to inform closed-loop neuromodulation (26). One emerging technique that may be useful in this regard is brain oscillationsynchronized TMS, which uses real-time electroencephalography (EEG) to trigger TMS pulses depending on the oscillatory phase of the EEG signal (27).…”

Transient amplitude modulation of alpha-band oscillations by short-time intermittent closed-loop tACS

“…One prominent recent study with phased-locked closed-loop stimulation was presented by Mansouri et al (2018). By using intermittent stimulation with very short (5 ms) square-wave pulses and an artifact removal procedure using a spline interpolation (Waddell et al, 2009), they were able to extract the artifact-free EEG signal and thus control for the actual phase locking of delivered stimulation and ongoing oscillation in alpha and theta bands.…”