Phase‑locked bilateral DBS

Phase‑locked bilateral Deep Brain Stimulation is a cutting-edge is of the neuromodulation strategies where stimulation on both sides of the brain is synchronized (or phase-locked) to specific neural oscillatory phases, rather than delivering constant or independently timed pulses.

🔍 What is it? In conventional bilateral DBS, each electrode (left and right hemisphere) delivers pulses independently, usually at high frequency (e.g., 130 Hz) without reference to ongoing brain activity.

Phase-locked bilateral DBS, on the other hand, involves:

Real-time monitoring of oscillatory brain activity (often via local field potentials, LFPs).

Delivering stimulation timed to specific phases (e.g., peak or trough) of tremor- or pathology-related oscillations.

Coordinating stimulation across both hemispheres in a controlled phase relationship — either in-phase, anti-phase, or some fixed delay (e.g., 180°, 90°).

⚙️ Why does phase matter? Many brain pathologies, especially tremor, involve abnormal synchronous oscillations between hemispheres or within a network. Modulating the timing of stimulation rather than just the intensity or frequency can:

Reduce pathological synchrony more effectively

Avoid stimulation-induced side effects (e.g., dysarthria from bilateral high-frequency pulses)

Potentially allow for lower energy consumption

🧠 Applications Postural tremor, especially in essential tremor (ET) and Parkinson's disease (PD)

Conditions with bilateral oscillatory coupling

Research suggests that phase-locked bilateral DBS may outperform traditional open-loop DBS for certain symptoms by desynchronizing tremor-related activity.

In a prospective analysis of archival limb acceleration data in nine essential tremor (ET) patients, plus a pilot bilateral phase-locked DBS intervention in one ET and one dystonic tremor (DT) patient.

He et al. from the:

- Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. - Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. - Department of Bioengineering, Imperial College London, London, UK. - Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, University of Cologne, Cologne, Germany. - Neurosciences Research Centre, Molecular and Clinical Sciences Institute, City St. George’s, University of London, London, UK.

published in Movement Disorders journal, to characterize asymmetries in postural tremor amplitude, frequency, and instability in bilateral hands of ET patients, assess how continuous high‑frequency DBS (cDBS) modulates these asymmetries, and explore feasibility/effects of bilateral phase‑locked DBS.

- Tremor power, amplitude instability, and frequency instability are significantly asymmetric across hands. cDBS reduces these asymmetries preferentially in the more tremulous side. Pilot bilateral phase‑locked DBS shows asymmetric modulation effects, implying phase‑ and side‑specific targeting may optimize tremor suppression with reduced energy delivery.

This study’s ambitiously titled “development” of bilateral phase‑specific DBS is misleading—only two patients received the intervention, lacking statistical power or generalizability. The nine‑subject archival analysis, while revealing asymmetry, relies on a narrow temporal window (3–5 days post-implant) subject to microlesion effects and surgical transient artifacts, undermining validity. The treatment effects of cDBS on tremor instability may simply reflect nonspecific high‑frequency suppression rather than insight into phase‑specific mechanisms. The phase‑locked DBS protocol suffers from poor phase synchronization (fixed delay ≈109 ms) and trivial sample size, rendering any “asymmetric effect” unsubstantiated. No clinical outcome measures (e.g., tremor rating scales) are reported, and energy savings are only theoretically mentioned. The manuscript overreaches by proposing patient‑specific therapeutic insights from preliminary, underpowered, biomechanical signal findings.

- Methodological novelty overshadowed by major limitations: small sample, timing artifacts, no clinical relevance, weak phase control.

- Postural tremor is not symmetric; continuous DBS mitigates this, but phase‑locked bilateral stimulation needs rigorous validation before clinical application.

- Intriguing preliminary data burdened by inadequate sample size and lack of clinical correlation; not yet practice‑changing.

- 3/10

Shenghong He et al. “Tremor Asymmetry and the Development of Bilateral Phase‑Specific Deep Brain Stimulation for Postural Tremor.” *Mov Disord.* Published online Jun 23, 2025. DOI:10.1002/mds.30275. PMID:40546090. Corresponding author: shenghong.he@ndcn.ox.ac.uk