DeepPLL: Synchronization of non-invasive brain stimulation to deep brain stimulation

Deep brain stimulation (DBS) is increasingly viewed as a network-level intervention, yet clinical practice typically targets a single brain structure per hemisphere. Coordinated multi-site stimulation may help probe and modulate distributed circuits, but additional invasive implantation is limited by safety and ethical constraints. Here, we present an approach to couple DBS with non-invasive transcranial alternating current stimulation (tACS) via precise phase synchronization. We introduce DeepPLL, an open-source interface device enabling real-time phase locking between DBS pulse trains and external stimulation like tACS. The system extracts DBS EEG artefacts using an isolated analogue front-end and stabilizes timing via a phase-locked loop (PLL) implemented in hardware or software. A digital phase-delay module with 1 degree resolution allows controlled adjustment of DBS phase, and low-jitter TTL outputs drive the external device. In two individuals with Parkinson's disease treated with subthalamic DBS, DeepPLL achieved reliable phase locking between DBS and motor-cortex tACS with sub-millisecond jitter in both PLL modes. This demonstrates feasibility of precise invasive-non-invasive stimulation synchronization in vivo and provides a platform for investigating phase-dependent network dynamics and plasticity.