Emerging neuromodulation techniques for treatment-resistant obsessive-compulsive disorder

In a peer-reviewed article published today in Brain Medicine, a European research team presents a focused review of emerging neuromodulation techniques for treatment-resistant obsessive-compulsive disorder (OCD). The article, "Neuromodulation techniques in obsessive-compulsive disorder: Current state of the art," examines how transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) are changing clinical approaches for patients who do not respond to traditional therapy or medication. Lead authors Dr. Kevin Swierkosz-Lenart and Dr. Carolina Viegas from Lausanne University Hospital, in collaboration with Prof. Luc Mallet from Paris-Est Créteil University, describe how each approach targets dysfunctional brain networks and how personalization, neuroimaging, and biomarker discovery could shape the next generation of psychiatric treatments.

Recalibrating the circuits of compulsion

OCD is a chronic neuropsychiatric disorder that affects roughly two percent of the population and often begins early in life. Many patients experience intrusive thoughts and repetitive actions that cause significant distress and impairment. Although serotonin reuptake inhibitors and cognitive behavioral therapy remain the standard of care, up to 60 percent of patients show incomplete or poor response.

This persistent challenge has prompted clinicians and neuroscientists to investigate the brain's electrical systems directly. Neuromodulation techniques aim to normalize abnormal activity in the interconnected network that underlies decision-making, emotion regulation, and the sense of internal control. "We are witnessing a convergence of clinical psychiatry and systems neuroscience," said Dr. Viegas. "Neuromodulation allows us to interact with the circuits that maintain obsessions and compulsions."

The review traces this transformation from early experimental attempts to a robust field guided by imaging, electrophysiology, and computational modeling. The authors emphasize that these tools do not replace existing therapies but complement them, creating a continuum from noninvasive stimulation to targeted surgical interventions.

Transcranial direct current stimulation: Gentle current, evolving evidence

Transcranial direct current stimulation delivers low-intensity electrical current through scalp electrodes, altering the excitability of cortical neurons. By shifting resting membrane potentials, it can subtly influence the dynamics of cortical and subcortical circuits implicated in OCD.

In recent studies, researchers have explored whether applying anodal or cathodal currents over regions such as the pre-supplementary motor area (pre-SMA) or orbitofrontal cortex (OFC) can reduce hyperactivity in the cortico-striato-thalamo-cortical loops associated with compulsive behavior. Early trials have yielded mixed results. Some report modest improvements, while others show little difference from sham stimulation. The authors attribute these inconsistencies to variations in electrode placement, current intensity, and session duration across studies.

"tDCS remains appealing because it is accessible and safe," said Dr. Swierkosz-Lenart. "But we need rigorous standardization and larger trials before it becomes part of mainstream clinical care." According to the review, future progress will depend on high-quality randomized trials using electric-field modeling, and objective biomarkers such as neuroimaging measures of connectivity or electrophysiological changes.

The paper notes that tDCS is well tolerated, with side effects typically limited to transient tingling or mild redness of the skin. Its portability and cost-effectiveness make it an attractive candidate for home-based interventions under professional supervision, once validated protocols are established.

Repetitive transcranial magnetic stimulation: Noninvasive modulation with growing clinical confidence

Repetitive transcranial magnetic stimulation (rTMS) uses rapidly changing magnetic fields to induce electric currents in specific cortical regions. Depending on frequency and site, stimulation can either increase or decrease neuronal activity. In 2018, the U.S. Food and Drug Administration approved deep rTMS for treatment-resistant OCD, targeting the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC).

Since then, a growing number of controlled trials and meta-analyses have confirmed that rTMS can produce significant symptom improvements, particularly when applied to the dorsolateral prefrontal cortex (DLPFC) or supplementary motor area (SMA). These targets are part of the brain's cognitive control network, which plays a central role in regulating intrusive thoughts and behavioral inhibition.

"rTMS represents the first noninvasive neuromodulation technique to achieve regulatory approval for OCD," said Dr. Viegas. "It has demonstrated clinical benefits, but we are still learning how to tailor parameters to the individual patient."

The review highlights variability across stimulation protocols. Some studies suggest that low-frequency inhibitory stimulation over hyperactive regions such as the SMA yields the best results, while others point to high-frequency excitatory protocols over hypoactive prefrontal areas. This diversity underlines the need for personalized targeting, potentially guided by neuroimaging data and neurophysiological markers.

Side effects are generally mild and transient, including scalp discomfort, tingling, or headache. The risk of seizure is extremely low when safety guidelines are followed. The authors also discuss theta-burst stimulation (TBS) and accelerated rTMS protocols that aim to achieve faster clinical effects through condensed treatment sessions. Though promising, these approaches require further validation in OCD populations.

Deep brain stimulation: Precision therapy for the most resistant cases

For patients whose OCD remains severe and refractory to all other therapies, deep brain stimulation has become an established and clinically validated treatment option.. The procedure involves implanting thin electrodes into specific deep brain regions, which are then connected to an implanted pulse generator that continuously delivers electrical stimulation.

DBS has shown sustained efficacy in several randomized controlled trials. According to the Brain Medicine review, the most effective targets include the bed nucleus of the stria terminalis (BNST), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAc), and subthalamic nucleus (STN). Across multiple studies, stimulation in these areas has led to symptom reductions ranging from 35 to 60 percent on the Y-BOCS scale, with long-term response rates of up to two-thirds of patients.

"DBS offers hope for individuals who have exhausted every other form of therapy," said Dr. Swierkosz-Lenart.

Instead of focusing on a single anatomical location, researchers are now interested in diffusion tractography and connectomic mapping to identify the white-matter pathways most associated with clinical improvement. Stimulating along these optimized fiber bundles can produce better results, even if electrode placements vary slightly between patients.

The review also details the emerging field of closed-loop DBS, where implanted systems record neural signals in real time and automatically adjust stimulation in response to brain activity. This approach could reduce side effects and enhance precision. Early evidence suggests that specific patterns in low-frequency oscillations within OCD-related circuits may serve as biomarkers for symptom states, potentially enabling dynamic, adaptive therapy.

DBS is generally safe when performed in specialized centers. The most common complications are minor and reversible, such as transient mood changes or local discomfort. Serious adverse events like hemorrhage or infection are rare. The authors caution that extensive follow-up and multidisciplinary management remain essential, especially as adaptive technologies evolve.

Personalization, ethics, and the next decade

The review concludes that neuromodulation represents one of the most exciting frontiers in psychiatry, but also one of the most complex. A central theme across all three modalities is personalization-the idea that stimulation parameters, targets, and protocols should be adjusted to match each patient's unique brain anatomy and symptom profile.

"Moving forward, we must integrate neuroimaging, electrophysiology, and computational modeling into daily clinical decision-making," said Dr. Viegas. "That is how we will achieve true precision psychiatry."

The authors call for harmonized international standards to enable cross-study comparisons and improve reproducibility. They also highlight the importance of addressing ethical considerations surrounding invasive interventions, data privacy, and informed consent. Access and equity remain key concerns, as high costs and specialized infrastructure can limit availability outside major academic centers.

Despite these challenges, the tone of the review is cautiously optimistic. With the increasing use of imaging-based targeting and adaptive stimulation, the field is poised to enter a phase of more individualized, data-driven therapy. "We are moving," the authors write, "toward a model of psychiatry that listens to the brain directly-one that adapts treatment as neural activity changes."