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

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.