Qualitative review of reported parameter ranges in focused ultrasound neuromodulation

Focused ultrasound (FUS) is a promising noninvasive modality for neuromodulation, with the ability to induce both inhibitory and excitatory neural effects. However, significant variation in reported acoustic parameters, experimental models, and outcome measures has limited comparability across studies and slowed clinical translation. To address this gap, this review synthesizes the limited available evidence describing how stimulation parameters—including frequency, pressure amplitude or intensity, duty cycle, pulse repetition frequency (PRF), exposure duration, and temporal stimulation pattern—can be associated with neuromodulatory outcomes such as inhibitory and excitatory effects, while highlighting current limitations and critical gaps found in the preliminary and heterogeneous nature of the existing literature. The authors reviewed ten peer-reviewed experimental and early translational studies that report explicit acoustic parameters (frequency, pressure amplitude/intensity, duty cycle, pulse repetition frequency, and exposure duration) along with measurable neural, structural, or behavioral outcomes, encompassing rodent, ex vivo, and human motor cortex models. Inhibitory responses including hippocampal long-term depression and motor-evoked potential suppression were most commonly associated with lower intensities, longer sonication durations, continuous stimulation paradigms, or specific parameter interactions favoring reduced cortical excitability. Conversely, repeated low-intensity pulsed ultrasound at moderate PRFs (∼500 Hz) and higher peak negative pressures (≈0.4–0.5 MPa) was associated with increased dendritic spinogenesis, increased excitatory postsynaptic activity, and improved memory performance. In addition, multiple studies demonstrated a capacity for bidirectional modulation depending on stimulation pattern or parameter definition alone. These findings suggest that neuromodulatory direction is governed by interacting acoustic and temporal parameters such as PRF, pressure amplitude, and stimulation duration, rather than single-variable thresholds. However, the limited number of controlled studies, heterogeneity in experimental design, and ongoing technical challenges—including skull attenuation, targeting verification, and safety considerations—preclude definitive parameter mapping at present. With FUS being an evolving technique with possible therapeutic potential, standardized reporting and dose–response modeling remain essential for establishing reliably tunable neuromodulatory protocols.