Frequency-Dependent Modulation of the Prefrontal Cortex by Low-Intensity Focused Ultrasound: Impact on Mesolimbic
Greatness O Olaitan1, Akhabue K Okojie2, Wendy J Lynch2
1Department of Chemistry, University of Virginia, Charlottesville, VA, 22904.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Low-intensity focused ultrasound (LIFU) can selectively alter dopamine release in the brain. Frequency tuning of LIFU applied to the prelimbic cortex (PLC) precisely controls excitation or inhibition of nucleus accumbens (NAcc) dopamine signaling.
Area of Science:
- Neuroscience
- Neuromodulation
- Neurotransmission
Background:
- Synchronized neural oscillations are crucial for cognitive functions.
- Low-intensity focused ultrasound (LIFU) shows potential for modulating neurotransmission.
- Targeted neuromodulation requires precise control over neural circuits.
Purpose of the Study:
- To investigate the effects of frequency-modulated LIFU on dopamine release and neural activity.
- To determine if LIFU can selectively excite or inhibit dopaminergic signaling in the nucleus accumbens (NAcc) core.
- To explore the influence of oscillation frequency and sex on LIFU's neuromodulatory effects.
Main Methods:
- Frequency-modulated LIFU was applied to the prelimbic cortex (PLC) in rats.
- Dopamine release in the NAcc core was measured using electrochemical methods.
- Neuronal and astrocytic activity was assessed via cFOS and GFAP expression.
- Histological analysis was performed to evaluate cell viability.
Main Results:
- LIFU modulated NAcc dopamine release (excitation or inhibition) for up to 90 minutes, dependent on frequency and sex.
- Specific frequency combinations (e.g., theta-coupled beta) reduced dopamine release and GFAP levels.
- Other frequencies (e.g., theta-coupled gamma) increased dopamine release, with sex-specific responses.
- LIFU elevated neuronal activation (cFOS) and, in some cases, astrocytic marker (GFAP) in the PLC without causing cell death.
Conclusions:
- Frequency-tuned LIFU stimulation of the PLC offers a novel method for selective neuromodulation.
- This approach can precisely control dopaminergic signaling in the NAcc.
- LIFU presents a promising tool for targeted manipulation of neurotransmission with potential therapeutic applications.


