Researchers from Boise State University and New York University have introduced a transformative approach to treating neurological disorders through Transcranial Radio Frequency Stimulation, or TRFS. This non-invasive brain stimulation technique promises to reach deep brain regions with precision, offering hope for millions affected by conditions like depression, Parkinson's disease, and chronic pain. Published recently in the journal Brain Stimulation, the study demonstrates TRFS's ability to modulate neural activity in live mice, suppressing or exciting brain cells without surgery.

The collaboration highlights the power of interdisciplinary work between engineering and neuroscience. Lead researcher Omid Yaghmazadeh, now an assistant professor at Boise State, developed the method during his postdoctoral training at NYU under mentor György Buzsáki, a renowned neuroscientist. Their findings show TRFS can induce controlled temperature changes that alter neuron firing, leading to measurable behavioral changes in animal models.

The Urgent Need for Better Neuromodulation Therapies

Neurological and psychiatric disorders impact one in six people worldwide, according to global health estimates. These include Alzheimer's disease, Parkinson's disease, depression, autism spectrum disorder, epilepsy, and anxiety. Traditional treatments like pharmaceuticals fail for up to 30 percent of patients with depression and epilepsy, leaving many without effective options. Invasive procedures such as Deep Brain Stimulation (DBS) require implanting electrodes through surgery, carrying risks like infection, speech impairments, balance issues, and long-term complications that affect patients and their families.

Non-invasive alternatives have emerged, but each has drawbacks. Transcranial Magnetic Stimulation (TMS) uses magnetic fields to induce currents but decays rapidly with depth, limiting it to superficial areas. Transcranial Electrical Stimulation (tDCS or TES) applies weak currents via scalp electrodes but lacks focality and deep penetration. Focused Ultrasound (TFUS) faces skull-induced distortions from acoustic scattering and refraction, reducing precision and causing side effects. A new method was desperately needed—one that penetrates deeply, targets specifically, and offers bidirectional control over neural activity.

Enter Transcranial Radio Frequency Stimulation (TRFS)

TRFS leverages radio frequency (RF) energy, the same type used safely in MRI scanners, stroke detection, and cancer hyperthermia treatments. Unlike everyday low-dose RF from cell phones, which studies show does not affect neurons, therapeutic doses create subtle thermal effects through dielectric heating—agitating water molecules and ions in tissue to raise temperature slightly (around 1.5 to 2 degrees Celsius). This thermal modulation influences ion channels in neurons, suppressing or exciting activity depending on the setup.

The technique's innovation lies in its contactless application. Custom stub antennas, operating at 945 MHz, are positioned near the skull without direct contact. Multiple antennas enable 'steerability,' focusing energy on pinpoint locations or broader areas, even the whole brain. RF waves pass through the skull unimpeded, unlike ultrasound, providing superior penetration.

Bimodal Operation: Pristine and RF-Genetics Modes

TRFS operates in two complementary modes, making it versatile for different therapeutic needs.

• Pristine Mode: Applied to intact, unmodified brain tissue. RF heating above 2°C suppresses activity in inhibitory parvalbumin (PV) interneurons in the cortex. These cells regulate excitatory neurons; their quieting reduces over-inhibition, potentially alleviating symptoms in depression, anxiety, and chronic pain where misfired inhibitory signals dominate.
• RF-Genetics Mode: Combines RF with genetic engineering. Researchers virally deliver genes for TRPV1 ion channels—heat-sensitive proteins naturally found in pain-sensing neurons—to target brain regions. When temperature exceeds 1.5°C, TRPV1 opens, flooding cells with calcium and exciting activity. This mode suits underactive circuits in Parkinson's or epilepsy.

The process unfolds step-by-step: First, antennas deliver pulsed RF (e.g., 15-45 seconds on-ramp at 6-20W, sustained at 3-8W, with recovery off-periods). Optical probes monitor temperature in real-time. Fiber photometry tracks calcium surges via GCaMP indicators, confirming neural changes. In behavioral tests, mice injected with MK-801 (mimicking hyperlocomotion in disorders) showed rotational biases: ipsilateral turns in pristine mode (suppression side slows), contralateral in RF-genetics (excitation speeds it up).

Proof-of-Concept Results from Mouse Models

In rigorous experiments with head-fixed and freely moving mice, TRFS proved reliable. Pristine mode induced dose-dependent PV interneuron suppression (linear correlation: β = −0.267, R=0.71). Specific Absorption Rate (SAR) reached up to 796 W/kg safely. Behavioral data from six mice per group showed significant rotation shifts (Wilcoxon P<0.01). RF-genetics effects persisted seven months post-injection, with excitation thresholds at ΔT ≈1.52°C.

These outcomes, detailed in the full study available here, mark the first in vivo demonstration of RF for direct neural modulation. No tissue damage occurred at therapeutic levels, affirming safety.

Advantages Over Conventional Techniques

TRFS stands out for its non-invasive nature, deep reach, and unique suppression capability—critical for disorders needing interneuron calming. RF-genetics introduces a novel paradigm, akin to optogenetics but without light or magnets, using endogenous channels.

Targeting Major Neurological Disorders

For depression and anxiety, pristine mode could dial down overactive PV interneurons, mimicking successful DBS outcomes without surgery. In Parkinson's, RF-genetics might excite basal ganglia circuits to restore movement. Epilepsy benefits from suppressing seizure foci, while autism and addiction may see circuit balancing. Chronic pain, often driven by central sensitization, responds to interneuron modulation.

Real-world context: Over 280 million people suffer depression globally; Parkinson's affects 10 million. TRFS could serve treatment-resistant cases, reducing reliance on lifelong drugs with side effects like weight gain or cognitive fog.

Researcher Insights and University Collaboration

"Deep brain stimulation surgeries are very heavy... People have been working for decades to find non-invasive ways," notes Yaghmazadeh. Buzsáki adds, "RF energy waves can effectively penetrate deep into tissue... with the unique advantage of suppressing neuronal activity."

Boise State's College of Engineering provides RF expertise, while NYU's Neuroscience Institute offers cutting-edge electrophysiology. Yaghmazadeh's lab now advances TRFS in mice, probing electromagnetic-nervous system interactions. More at Boise State news and NYU Langone.

Challenges, Safety, and Path to Human Trials

Safety data shows no neuronal damage; everyday RF (phones) is inert, therapeutic doses controlled. Challenges include phased-array antennas for human-scale focusing and non-invasive gene delivery (e.g., via ultrasound). Ethical considerations for RF-genetics mirror gene therapy debates.

Next: Scale to primates, refine dosing, clinical trials for focal disorders. NIH funding (R01NS113782) supports translation.

Implications for Neuroscience and Higher Education

This breakthrough underscores university research's role in health innovation. It opens doors for careers in neuroengineering, blending electrical engineering with biology. Students at institutions like Boise State gain hands-on RF systems experience, preparing for neuromodulation's future.

Broader impacts: Accelerates precision medicine, reduces healthcare costs (DBS ~$100K+ per patient), improves quality of life. As neurotech evolves, collaborations like this exemplify academic excellence.

Future Outlook: Transforming Brain Health

TRFS could redefine non-invasive brain stimulation, bridging noninvasive therapies and surgical precision. Ongoing refinements promise wearables or clinic devices, empowering patients. For researchers, it invites exploration of RF-neuron interactions, potentially unlocking new therapies. This Boise State-NYU synergy signals a bright era in neuromodulation.

Photo by Markus Winkler on Unsplash