Noninvasive “deep brain” stimulation technique shows early promise for Parkinson’s

A novel, noninvasive brain stimulation approach—known as transcranial temporal interference stimulation (TIs)—may offer a new way to treat motor symptoms in Parkinson’s disease without the need for surgery, according to a pilot study appearing in eBioMedicine, published by The Lancet. The technique, which uses overlapping electrical currents to selectively target deep brain regions, significantly improved movement in patients compared with a sham treatment when targeting the subthalamic nucleus.

Parkinson’s disease is a progressive neurological disorder that affects movement, often causing tremor, stiffness, and slowed motion. One of the most effective treatments for advanced symptoms is deep brain stimulation (DBS), which involves implanting electrodes into the brain. TIs may be able to achieve a similar effect—targeting the same deep brain structures—but entirely from outside the skull, using carefully calibrated electrical fields delivered through the scalp.

In the randomized, double-blind, crossover study, entitled, “Transcranial temporal interference stimulation targeting the subthalamic region for motor symptoms in Parkinson’s disease: a pilot, randomised, double-blind, sham-controlled crossover study,” 30 people with early- to mid-stage Parkinson’s disease received a single 20-minute session of individualized TIs targeting the subthalamic region—a key node in the brain’s motor control network—as well as a sham or placebo treatment in a separate session.

The benefits were measurable immediately after stimulation and persisted for at least an hour. Using the Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS‐UPDRS), Part III, a standard to assess motor symptoms in Parkinson's disease, TIs produced significantly greater improvements than the sham condition at all timepoints. The results showed a marked difference: 70% of participants experienced clinically meaningful improvement after TIs, compared with just 15% after the sham treatment.

The strongest effects were seen in bradykinesia (slowness of movement) and tremor—two of the most disabling symptoms of Parkinson’s—while improvements in rigidity and balance-related symptoms were less consistent.

Crucially, TIs was well tolerated. No serious adverse events were reported, and mild sensations such as tingling or warmth occurred at similar rates in both active and sham conditions. Because the method is noninvasive, it avoids surgical risks and ongoing device management associated with implanted brain stimulators.

“TIs represents a fundamentally different approach to non-invasive neuromodulation—one that can reach deep brain targets without surgery,” said Alvaro Pascual-Leone, MD, PhD, one of the researchers and the Medical Director, The Deanna & Sidney Wolk Center for Memory Health, Hebrew SeniorLife. Pascual-Leone is also a Professor of Neurology at Harvard Medical School. “We also need to find out which is the best target in the brain for a given effect and a given patient. Other deep brain nuclei may induce greater benefit and be able to affect different core symptoms of Parkinson’s Disease.”

“These early results are promising, so we are already moving forward, together with our collaborators from Shanghai University of Sport, the UK and Germany, to conduct larger studies applying multiple sessions of stimulation in subsequent days to induce lasting effects and determine how long the benefits can last, how treatments should be spaced, and which patients are most likely to respond,” said Junhong Zhou, PhD, Co-Corresponding author, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife.

“One of the most promising aspects of this work is the ability to individualize stimulation based on each patient’s own brain anatomy. That level of precision could become increasingly important as we learn how to tailor neuromodulation therapies to different Parkinson’s symptoms and different patients,” said Brad Manor, PhD, Senior Scientist, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife. ““A noninvasive technique like TIs could someday provide a valuable new option either before surgery is considered or alongside existing therapies.”

The researchers caution that the study was designed as a pilot trial and evaluated only short-term effects after a single session. Future research will need to test repeated treatments, longer follow-up periods, and whether TIs can deliver sustained improvements in everyday functioning.

If confirmed in larger trials, transcranial temporal interference stimulation could open the door to a new class of noninvasive therapies, bringing deep–brain stimulation–like benefits to a broader population of patients without the need for surgery.

In addition to Pascual-Leone, Zhou and Manor, the study’s other researchers were Chenhao Yang, PhD, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China; Yongxin Xu, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of  Sport, Shanghai; Yichao Du, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of  Sport, Shanghai; Xiaonan Shen, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Tingting Li; Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Nan Chen, PhD, Department of Rehabilitation, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; Yulian Zhu, PhD, Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai; Lingyan Huang, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Jiaojiao Lü, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Lu Li, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Zhenyu Qian, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai; Zhen Wang, PhD, School of Martial Arts, Shanghai University of Sport, Shanghai; Ulf Ziemann, MD, Department of Neurology and Stroke, and Hertie Institute for Clinical Brain Research, University of Tübingen, Germany; Nir Grossman, PhD, Department of Brain Sciences, and UK Dementia Research Institute, Imperial College London; Chencheng Zhang, MD, Department of Neurology, Neurosurgery, Psychiatry and Neuroscience, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai; and Yu Liu, PhD, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai.

About Hebrew SeniorLife
Hebrew SeniorLife is a national leader working to create a world where aging is defined by possibility, not limitation. We care for more than 4,500 older adults each day across seven campuses throughout Greater Boston, and offer support for families in the aging journey. Our services include in-home care, outpatient therapies, an outpatient memory clinic, short- and long-term inpatient care, hospice, independent and assisted living, and affordable housing with services. We conduct influential research on aging at our Hinda and Arthur Marcus Institute for Aging Research, which has a grant portfolio of $87 million, and train future health care workers at the Lunder CareForce Institute. Hebrew SeniorLife is a Harvard Medical School affiliate.

About the Hinda and Arthur Marcus Institute for Aging Research
Scientists at the Marcus Institute seek to transform the human experience of aging by conducting research that will ensure a life of health, dignity, and productivity into advanced age. The Marcus Institute carries out rigorous studies that discover the mechanisms of age-related disease and disability; lead to the prevention, treatment, and cure of disease; advance the standard of care for older people; and inform public decision-making.