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Advancing Deep Brain Stimulation Through Better Targeting and Smarter Devices

Advancing Deep Brain Stimulation Through Better Targeting and Smarter Devices

Jun 26, 2026PAO-06-26-PA-23

Key Takeaways

  • Deep brain stimulation (DBS) involves stimulation of areas of the brain with electrical pulses from implanted electrodes. It has been shown to be effective for management of some symptoms associated with Parkinson’s disease, epilepsy, and obsessive–compulsive disorder. It has potential for treatment of symptoms that occur with various psychiatric disorders as well.

  • Despite its proven clinical benefits, DBS use is limited owing to its high cost, need for specialized clinical care, and the often lengthy periods required for parameter adjustment.

  • Technical advances, including new contact designs and stimulation protocols, advances in software capabilities, automated and adaptive stimulation programs, and longer-lasting and more efficient pulse generators, could enable application of DBS to more indications and greater patient access.

  • Some simple, inexpensive, non-invasive techniques capable of achieving DBS may provide attractive alternatives if early clinical data is confirmed.

Alternative to Aggressive Surgical Treatment

Deep brain stimulation (DBS) involves the insertion of one or more electrodes into specific areas of the brain. Wires from the electrodes, laid under the skin, are connected to a battery-powered electrical pulse generator implanted in the upper chest area. Electrical impulses with specific amplitudes emitted by the generator stimulate the part of the brain containing the electrodes. This stimulation affects cell and neurotransmitters in the brain to help control symptoms of certain neurodegenerative diseases.1

Initially, DBS was approved only for the treatment of tremors in Parkinson’s diseases (PD) patients. It is an attractive alternative to the traditional approach, which involves surgical ablation of the ventral intermediate nucleus of the thalamus or bilateral thalamotomy. This surgery, however, has a high risk for impairment of speech and swallowing.2

DBS is generally considered a low-risk treatment.3 It involves minimal permanent changes to the brain, and the pulse generator can be removed if it is determined DBS should be halted.1 In addition, the adjustment of the stimulation parameters is achieved without the need for any further surgery. There is, of course, always some risk with surgery. It is also possible for the electrical DBS pulses to affect non-targeted brin tissue which may impact behavior, balance, and speech. Unlike with bilateral thalamotomy, however, these effects can often be ameliorated by adjusting the stimulation parameters.

Because the electrodes are very small and must be placed deep within the brain, the specific locations for their placement are determined by not only considering the condition to be treated but also using advanced anatomical imaging technologies such as magnetic resonance imaging (MRI) and computed tomography (CT).4 Typically, a stereotactic frame is attached to the patient to provide a coordinate system for reference, and microelectrode recording (MER) is used for electrophysiological guidance. Patients are usually awake so that the effects of stimulation can be observed to confirm proper placement.

30 Years of Approved Therapy

The first DBS treatment was approved by the U.S. Food and Drug Administration (FDA) in 1997 for essential tremor and PD-related tremor.2 In 2003, additional approvals were granted for subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS for PD. Also in 2003, the FDA granted a humanitarian device exemption for STN DBS and GPi DBS for treatment of primary generalized and segmental dystonia (involuntary, sustained, or intermittent muscle contractions), followed by another exemption in 2009 for obsessive–compulsive disorder (OCD).

Since then, additional devices have been approved, and off-label/experimental use has also expanded for treatment of additional conditions including epilepsy, depression, Tourette’s syndrome, cluster headaches, chronic pain, obesity, Alzheimer's disease, addiction, the minimally conscious state, other movement-related disorders, including chorea or exaggerated fidgeting often occurring in patients with Huntington's disease.1,4 Generally, DBS is reserved for the treatment of patients that have not responded well to treatment with leading drugs, such as levodopa.

For movement disorders, DBS electrodes are typically placed within the STN, GPi, and the ventralis intermedius nucleus of the thalamus, while for psychiatric conditions (e.g., OCD, depression), electrodes are generally located in the subcallosal cingulate gyrus, the anterior limb of the internal capsule, and the nucleus accumbens.4

It is important to note that DBS does not cure any conditions or slow their progression; it helps patients manage symptoms. For instance, thalamic DBS has been shown to be highly effective for treatment of essential and PD tremor, with reduction of tremor, rigidity, and slowness of movements (bradykinesia), as well as adverse side effects associated with levodopa.2 It is less effective, however, for action tremor, which occurs with multiple sclerosis, trauma, or stroke due to blockage of cerebellar outflow pathways.

Patients and their physicians must take into account several factors when choosing a DBS device approved by regulatory authories.5 Some pulse generators contain rechargeable batteries, while others do not. Some DBS devices allow patient programming and others do not. Of those that do, programming may be achieved in various ways, and one or another approach may be more suitable. Doctors also may have experience with specific devices

Much Still to Learn

While DBS has been shown to be successful in treating symptoms of neurodegenerative and psychiatric diseases, that success has come despite a lack of consensus on the how it alleviates those systems.1 Initially it was thought that electrical stimulation inhibited neuronal activity in the targeted area. It was then discovered that activity in downstream nuclei increased. Positron emission tomography studies then revealed increased cortical blood flow during thalamic DBS, which also suggests activation at the stimulated site. It was hypothesized that stimulation inhibits the cell body but excites axons. It was thus concluded that the electrical stimulation helps regulate activity, with the effect spreading through the basal ganglia (surrounding fiber pathways) with improved information content across the neuronal network.1 The field of connectomics — the study and mapping of how neurons in the brain are structurally and functionally connected — will likely impact the design and targeting of DBS treatments for different conditions in the future.6

In June 2026, researchers from the Icahn School of Medicine at Mount Sinai reported the discovery of evidence indicating that DBS treatments result in remodeling of white matter pathways in the brain, which impacts communication across large-scale neural networks.7 This rewiring of brain circuits is thought to be particularly important in patients suffering from severe depression that do not respond to medications, psychotherapy, and electroconvulsive therapy but have sustained positive results with DBS in the callosal anterior cingulate cortex (cACC). DBS resulted in a greater number of myelinated oligodendrocytes and support cells in the white matter of the brain that help to promote the propagation of neural signals and a higher degree of myelination within the pathway

Technical Advances May Expand Access

Another issue with DBS beyond a lack of deep understanding on its mechanism(s) of action is its limited adoption. Several potential factors have resulted in this situation. DBS is an invasive therapy and it does require multiple visits for the surgery and postoperative programming. It also is very expensive, and insurance coverage is not always available.7

Advances in DBS technologies, both hardware and software, are anticipated to improve the process, expand the number of clinical applications, and increase patient access.6,8,9 New electrode/lead designs are enabling more targeted delivery of electric impulses and different stimulation patterns that result in better outcomes. Enhanced image-guided electrode placement (e.g., directional DBS) and programming are facilitating treatment setup and reducing the required number of office visits, while newer generators have improved energy efficiency and longer lifetimes.

New directional electrodes/leads, rather than simply producing a spherical electric field that can only have the polarity and pulse pattern adjusted, allow stimulation to be steered in a specific direction. They comprise multiple contacts that deliver stimulation in specific directions. Different numbers of contacts and contact designs allow more precise targeting of different parts of the brain when treating different conditions, typically at lower amplitudes. In addition, directional DBS enables expansion of the therapeutic window due to the lower and higher efficacy and side-effect thresholds, respectively.

Radially segmented electrodes, meanwhile, enable axial steering of the current toward the target area with minimal exposure of surrounding brain structures. A single-activated electrode (single-segment activation (SSA)) allows generation of tailored axially asymmetric fields. The use of current fractionalization, which distributes current of the same frequency between two or more contacts, provides more control of current delivery. It can be implemented either by rapidly alternating stimulation from the different contacts (interleaving) or activating all contacts simultaneously (coactivation). With the multiple independent current control (MICC) approach, the current for each contact is set independent of the others using multiple current sources, which allows for different amplitudes, pulse widths, and frequencies in different contacts, enabling the generation of more precisely shaped fields. The downsides of these systems are their greater complexity for placement and programming and their higher energy consumption.

Other new techniques being explored include high-frequency stimulation (HFS) and low-frequency stimulation (LFS).8,9 Variable frequency stimulation (VFS) alternates between HFS and LFS to improve both rigidity and tremor and freezing of gait and balance impairment, respectively, while reducing side effects. HFS has been found to address problems not corrected by traditional DBS, particularly axial symptoms. It also is thought to lead to greater neural plasticity, which has the potential to result in restored function within damage regions of the brain. Dual-frequency interleave–interlink (IL–IL), is an approach being explored as a means for simultaneously addressing both axial and appendicular (e.g., tremor) symptoms. In this case, two different LFS programs are interleaved on different leads placed so the overlapping stimulation region is optimal around a central contact through which HFS is applied. The HFS controls the appendicular symptoms, while the non-overlapping LFS regions address the axial symptoms. Burst cycling is a polyrhythmic stimulation pattern in which stimulation is turned on and off. In coordinated reset DBS, short high-frequency pulses are applied via burst cycling at lower amplitude through different contacts at different times to disrupt undesired synchronized neural activity.

Software advances, meanwhile, are enabling better identification of optimal locations for contact placement and for programming of implanted electrodes.6,8,9 Solutions are now available that use data from MRI and CT scans to reconstruct the brains of individual patients, including nuclei and fiber tracts in targeted regions. Systems can also analyze recorded electrophysiological responses during and after surgery. Analyses of this patient-specific data use advanced predictive modeling programs to support rapid development of customized DBS treatments that afford better clinical outcomes. Automated and remote programming are additional advances improving the patient experience with respect to DBS.

One important recent development has been the emergence of adaptive DBS (aDBS) systems, with at least one having received FDA approval.3 Rather than deliver continuous electrical pulses with constant properties, these devices detect changes in specific biomarkers and, using artificial intelligence and machine learning algorithms applying amplitude–responsive or phase-responsive strategies, adjust the nature of the delivered current in response.6,8,9 This approach is also referred to as close-loop DBS (CL DBS). Clinical trials have been limited to date, but initial results are promising. In one study of PD patients, adaptive DBS provided sustained symptom control with less stimulation time and better energy efficiency than traditional DNS systems. One key limitation of aDBS is the increased complexity and thus need for specialized clinical expertise.

Temporal Interference Stimulation: Nonsurgical DBS?

The need for invasive surgery may be one of the leading reasons why DBS, despite is clear benefits, has experienced limited adoption. However, there may be a non-surgical alternative. Temporal interference (TI) stimulation involves application of two high-frequency electrical currents to the skull to generate a low-frequency focal area where the two currents meet that can increase or decrease neuronal activity.10 Unlike most other external methods, this approach is able to reach deep into the brain.

Clinical studies are underway to explore the potential therapeutic benefits of TI for stroke, epilepsy, psychiatric disorders, dementia, PD, and other conditions. In addition to not requiring invasive surgery, TI has the advantages of requiring only inexpensive and widely available equipment (two pairs of head-mounted electrodes linked to portable current generators) and simple protocol. It is also simpler and safer than transcranial focused ultrasound, which is another technology being investigated for deep brain modulation. And it does not cause discomfort and can therefore be applied when patients are sleeping.

Application of magnetic fields in the kHz range to targeted areas of the brain has also been shown to stimulate brain activity within the hippocampus and may be another alternative to DBS.11

References

1. “Deep brain stimulation.” Mayo Clinic. 17 Mar. 2026.

2. Miocinovic, Svjetlana, et al.History, Applications, and Mechanisms of Deep Brain Stimulation.” JAMA Neurology. 70: 163–171 (2013).

3. “Deep Brain Stimulation (DBS).” National Institute of Neurological Disorders and Stroke. 13 Mar. 2026.

4. Grant, Ryan, Shaun E Gruenbaum, and Jason Gerrard.Anaesthesia for Deep Brain Stimulation: A Review.” Current Opinion in Anaesthesiology. 28: 505–510 (2015).

5. “Choosing a Deep Brain Stimulation Device.” Michael J. Fox Foundation. Accessed 23 Jun. 2026.

6. Foote, Avery, et al.A Comprehensive Review of Deep Brain Stimulation for Parkinson’s Disease: The History, Current State of the Art and Future Possibilities.Medicine in Novel Technology and Devices. 26: 100362 (2025).

7. “Deep Brain Stimulation Remodels Brain Wiring and Alters Functional Changes to Brain-Wide Networks, Landmark Depression Study Reveals.” Mount Sinai. 1 Jun. 2026.

8. Sandoval-Pistorius, Stephanie S, et al. Advances in Deep Brain Stimulation: From Mechanisms to Applications.” Journal of Neuroscience. 43: 7575–7586 (2023).

9. Della Torre, Attilio, et al. Innovative Developments in Deep Brain Stimulation Devices.” Interdisciplinary Neurosurgery. 40: 102035 (2025).

10. Smith, Jennie Erin.Overlapping Currents Can Tune the Deep Brain.Science. 391: 1188–1189 (2026).

11. Violante, Ines R, et al. Non-Invasive Temporal Interference Electrical Stimulation of the Human Hippocampus.” Nature Neuroscience. 26: 1994–2004 (2023).

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