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.
Highlights
Non-invasive brain stimulation is entering increasingly widespread use as both a research tool and a clinical intervention for neuropsychiatric disorders
Endogenous brain activity during stimulation is a key factor determining the effect of the stimulation (Herrmann et al, FIGURE 4 | (A–E) Polar histogram showing performance of theta stimulation in theta band for 4 different phase angles. (F–J) Polar histogram showing performance of theta stimulation in theta band for 4 different phase angles
Conventional ‘open-loop’ brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS), tDCS, or transcranial alternating current stimulation (tACS) that do not make efforts to synchronize their activity to the endogenous activity of the target brain region risk the possibility of an unwelcome heterogeneity in the magnitude, or even direction, of their effect
Summary
Non-invasive brain stimulation is entering increasingly widespread use as both a research tool and a clinical intervention for neuropsychiatric disorders. A Closed-Loop System for Non-invasive Brain Stimulation have been developed as ways to modulate brain activity (Polanía et al, 2018). While these methods have demonstrated applications in treating a number of neuropsychiatric disorders (Schulz et al, 2013; Kuo et al, 2014), they are still hampered by several important limitations. One such limitation is the heterogeneity of effect across individuals. Most non-invasive brain stimulation techniques use ‘open-loop,’ i.e., applying stimulation at a set protocol without feedback guidance from the actual activity of the target region. A ‘closed-loop’ system, in contrast, would read the activity of the target region and use this information to guide the parameters of stimulation: for example, the pattern, frequency, phase, or timing of stimulation
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