Nudge Zero: Deep-Brain Ultrasound Without Surgery

For decades, non-invasive neuromodulation has wrestled with a fundamental depth-focality trade-off. Technologies like Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) excel at modulating superficial cortical layers, but their energy diffuses as it penetrates deeper into the brain. To access deep subcortical structures such as the thalamus or the nucleus accumbens, clinicians have traditionally had to rely on invasive Deep Brain Stimulation (DBS) surgeries requiring implanted electrodes.

Nudge is working to bypass this surgical requirement entirely. Their current investigative clinical device, Nudge Zero, utilizes Low-Intensity Focused Ultrasound (tFUS) to non-invasively interface with millimeter-sized subregions deep within the brain. By moving past simple, physically adjusted single-transducer hardware, Nudge's new helmet architecture utilizes a high-channel-count acoustic phased array.

The Physics: Acoustic Beamforming and Phased Arrays

The core mechanism of tFUS relies on mechanical rather than electrical energy. Low-intensity ultrasound waves travel through soft biological tissue with minimal power loss, exerting localized, non-destructive mechanical pressure on cellular membranes and mechanosensitive ion channels. This pressure safely and reversibly alters neuronal excitability.

To focus this energy onto a deep brain target without affecting the surrounding cortex, Nudge utilizes a phased-array transducer system. Instead of physically moving a single ultrasound source around the skull, the Nudge Zero helmet embeds a high-density matrix of individual transducer elements.

Transducer Element 1 ───► ░░░\

Transducer Element 2 ───► ░░░░\───► [ Constructive Interference Peak ]

Transducer Element 3 ───► ░░░░/     (Millimeter-Sized Subregion)

Transducer Element 4 ───► ░░░/

                            ▲

                   [ Phase-Delayed Waves ]

By introducing precise electronic microsecond delays (phase-shifting) to the signals transmitted by each individual element, engineers can manipulate the geometry of the wavefront. The waves propagate through the brain, passing through superficial tissues under thresholds capable of triggering neural activation.

Only at the exact mathematical point where these waves intersect do their acoustic peaks align in phase, a phenomenon known as constructive interference. This creates a highly localized focus on the order of millimeters, allowing targeted disruption or excitation of circuits implicated in conditions like chronic pain, anxiety, and substance use disorder.

Challenge: The Cranial Acoustic Barrier

While the mathematical principles of constructive interference are straightforward in a homogenous medium like water, the human head presents a highly complex boundary environment. The primary obstacle is the human skull.

Bone has a significantly higher acoustic impedance and speed of sound compared to skin, muscle, and brain tissue. This causes three distinct physical phenomena that distort the beam:

• Severe Attenuation: The skull absorbs and scatters acoustic energy rapidly. To maintain an adequate signal-to-noise ratio at the deep target structure without overheating the bone, tFUS devices typically must operate at lower acoustic frequencies (often below 700 kHz).

• Phase Aberration: Skull thickness, density, and diploë (the porous inner layer of bone) vary continuously across an individual’s cranium. As different portions of the ultrasound wavefront hit different thicknesses of bone, they slow down unevenly. This desynchronizes the phases, causing the focal spot to defocus or shift away from the intended coordinates.

• Patient-Specific Simulation: To correct for phase aberration, Nudge Zero pairs with real-time Magnetic Resonance Imaging (MRI) guidance. Before stimulation, patient-specific structural MRI or CT scans are processed through high-fidelity acoustic propagation simulations (often utilizing pseudo-spectral time-domain methods). These models calculate the precise phase delay corrections required for each individual transducer element to guarantee that the acoustic focus lands exactly on the targeted subcortical voxel.
  Focused Ultrasound Foundation

Advantages of the Nudge Architecture

• Millimeter-Level Focality at Depth: Nudge Zero achieves spatial precision that matches or exceeds invasive surgery, completely outclassing alternative non-invasive methods like TMS.

• Dynamic Electronic Steering: Because the focus is controlled entirely via software phase-delays, clinicians can steer the acoustic beam across different nodes of a functional network (e.g., shifting from the VIM thalamus to the dentatorubrothalamic tract) in milliseconds without any physical moving parts.

• Reversible Modulation: Unlike high-intensity focused ultrasound (HIFU), which permanently ablates tissue to treat essential tremor, tFUS uses low-intensity mechanical energy to reversibly modulate circuits without causing thermal or structural damage.

Limitations and Hurdles

• Bulky Hardware Infrastructure: The current Nudge Zero iteration relies on multi-million dollar MRI suites for real-time visualization, planning, and safety tracking. This heavily restricts throughput and keeps the treatment bound to specialized clinical environments.

• The Miniaturization Paradox: Moving from an MRI-guided clinical helmet to a future, consumer-grade at-home headphone form factor introduces immense technical friction. Eliminating the MRI means the device must handle skull-aberration corrections natively. This would require embedding low-power ultrasound imaging arrays into the same headset to map the skull and brain structure on the fly, a massive hardware integration challenge.

• Transducer Heating and Thermal Safety: Continuous or high-duty-cycle sonication can lead to heat accumulation at the bone-soft tissue interface. Managing the thermal index through advanced cooling mechanisms or strict pulsing protocols is an ongoing design constraint.

The Future: From Clinical Arrays to Consumer Form Factors

Nudge’s 100M Series A funding underscores the industry's belief that ultrasound is the most promising candidate for a whole-brain non-invasive interface. While the Nudge Zero clinical trial targeting essential tremor and chronic pain is establishing the foundational safety and parameter guidelines, the long-term roadmap requires translating these heavy phased arrays into a portable, wear-and-forget device. Success will ultimately rest on whether advanced computational modeling can entirely replace the need for real-time MRI guidance.

References

Bystritsky, A., Korb, A. S., Douglas, P. K., Cohen, M. S., Melega, W. P., Mulgaonkar, A. P., ... & Yoo, S. S. (2011). A review of low-intensity focused ultrasound pulsation. Brain Stimulation, 4(3), 125-136. https://doi.org/10.1016/j.brs.2011.03.007

Riis, T. S., Feldman, C. H., Losser, A., King, C. R., & Kubanek, J. (2024). Noninvasive targeted modulation of pain circuits with focused ultrasonic waves. Pain, 165(11), 2450-2461. https://doi.org/10.1097/j.pain.000000000000332

Rezai, A. R., Mahoney, J. J., Ranjan, M., Haut, M. W., d'Audiffret, A. C., Chemetov, A., ... & Hodder, S. L. (2025). Focused ultrasound neuromodulation: Exploring a novel treatment for severe opioid use disorder. Biological Psychiatry, 97(2), 112-121. https://doi.org/10.1016/j.biopsych.2025.01.001

Wang, Z., Zhang, M., Zheng, Y., & Yuan, Y. (2026). Parameter-determined effects: Advances in transcranial focused ultrasound for modulating neural excitation and inhibition. Bioengineering, 13(1), 24. https://doi.org/10.3390/bioengineering13010024