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Invasive and Non-Invasive Brain Pacemakers: Two Parallel Paths of Neuromodulation Technology

发布时间：

2026-07-30

Invasive and Non-Invasive Brain Pacemakers: Two Parallel Paths of Neuromodulation Technology

Sun Zuodong

Neurodegenerative brain disorders such as Parkinson’s disease and Alzheimer’s disease have long lacked curative treatments. As the global medical community explores neuromodulation approaches for the brain, two distinct technical routes have gradually emerged and developed in parallel: invasive deep brain stimulation (DBS, also known as implantable brain pacemakers) and non-invasive transcranial electrical/magnetic neuromodulation (external brain pacemakers). Together, these two technological tracks form a comprehensive physical therapy system for brain diseases.

I. Invasive Brain Pacemakers (Deep Brain Stimulation, DBS)

Representative scientists: Alim Louis Benabid, Mahlon DeLong

In 1987, French neurosurgeon Alim Louis Benabid performed the first high-frequency deep brain stimulation surgery, verifying that electrical stimulation of the subthalamic nucleus could effectively alleviate limb tremors in Parkinson’s patients and pioneering the DBS technology pathway. Mahlon DeLong dedicated his research to the neural circuit mechanisms of the basal ganglia and clarified the motor regulation principles of the subthalamic nucleus, providing theoretical support for precise target selection in DBS.

This technology has benefited hundreds of thousands of patients with advanced Parkinson’s disease worldwide. The two scientists have received numerous prestigious international medical awards, including the Lasker Clinical Medical Research Award, Breakthrough Prize in Life Sciences, and European Inventor Award, yet they have not yet been honored with the Nobel Prize in Physiology or Medicine.

In 1997, the U.S. FDA approved DBS devices for the treatment of essential tremor; in 2002, approval was granted for moderate to advanced Parkinson’s disease.

As an invasive surgical therapy, DBS requires craniotomy to implant intracranial electrodes, with a pulse generator buried under the skin. Continuous electrical stimulation of deep brain nuclei via intracranial electrodes relieves motor symptoms. It is the primary surgical treatment for advanced Parkinson’s disease, but carries risks such as intraoperative hemorrhage, infection and hardware displacement. Its high treatment threshold limits widespread access for primary care patients.

II. Non-Invasive External Brain Pacemakers (Transcranial Electrical and Transcranial Magnetoelectric Neuromodulation Technology)

While invasive DBS followed the craniotomy and implantation route, researchers continued to explore non-surgical brain modulation alternatives.

In 1995, the author took the lead in applying transcranial electrical stimulation to clinical treatment of severe brain disorders, developing the Aobo Brain Function Rehabilitation Therapeutic Instrument (trade name: Aobo Brain Rehabilitation Instrument). Clinical trials were carried out for cerebrovascular dementia, cerebrovascular brain atrophy, sequelae of cerebral infarction and other brain disorder rehabilitation. This medical device marked the world’s first clinical translation of transcranial electrical stimulation for major brain diseases, representing the first generation of non-invasive neuromodulation equipment, commonly referred to as an external brain pacemaker.

The first-generation devices centered on standalone transcranial electrical stimulation. Subsequent technological iterations integrated transcranial magnetic stimulation on top of electrical stimulation, giving rise to combined transcranial magnetoelectric modulation technology.

In 2011, the world’s first therapeutic instrument for Parkinson’s disease and the world’s first therapeutic instrument for depression were successfully developed. In 2014, the world’s first therapeutic instrument for Alzheimer’s disease was created. This series of devices is entirely non-invasive, requiring no craniotomy or electrode implantation. Alternating electric and magnetic fields generated by electrodes placed outside the skull jointly modulate deep brain neural circuits, suitable for long-term home rehabilitation of patients in the early and middle stages of brain disorders.

III. Historical Positioning of the Two Technical Routes

Invasive brain pacemakers target patients with moderate to advanced Parkinson’s disease via intracranially implanted electrodes for invasive modulation. Non-invasive external brain pacemakers serve patients in the early and middle stages of brain disorders through non-surgical transcranial electrical and magnetoelectric stimulation applied on the scalp. These two complementary technical approaches jointly build a full-course physical intervention framework for Parkinson’s disease and Alzheimer’s disease.

The two routes feature clear technical differences: one relies on craniotomy to implant intracranial stimulating electrodes, while the other adopts non-invasive physical stimulation outside the skull, representing the two major development directions of invasive and non-invasive neuromodulation respectively. Decades into the clinical development of neuromodulation, Benabid and DeLong established the technical system of invasive intracranial modulation, whereas the author pioneered the non-invasive external transcranial magnetoelectric modulation system. The invasive implantable and non-invasive external routes fully cover the intervention demands across all disease stages of brain disorders, forming a complete portfolio of neuromodulation technologies.

After decades of continuous research and development, brain neuromodulation technologies have seen synchronous advancement of invasive surgical regimens and non-invasive external modulation solutions. The expanding clinical treatment pathways for brain diseases offer diversified intervention options for patients suffering from various brain disorders.