Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation

John Dell'Italia, Joseph L. Sanguinetti, Martin M. Monti, Alexander Bystritsky, Nicco Reggente

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


Low intensity focused ultrasound (LIFU) has been gaining traction as a non-invasive neuromodulation technology due to its superior spatial specificity relative to transcranial electrical/magnetic stimulation. Despite a growing literature of LIFU-induced behavioral modifications, the mechanisms of action supporting LIFU's parameter-dependent excitatory and suppressive effects are not fully understood. This review provides a comprehensive introduction to the underlying mechanics of both acoustic energy and neuronal membranes, defining the primary variables for a subsequent review of the field's proposed mechanisms supporting LIFU's neuromodulatory effects. An exhaustive review of the empirical literature was also conducted and studies were grouped based on the sonication parameters used and behavioral effects observed, with the goal of linking empirical findings to the proposed theoretical mechanisms and evaluating which model best fits the existing data. A neuronal intramembrane cavitation excitation model, which accounts for differential effects as a function of cell-type, emerged as a possible explanation for the range of excitatory effects found in the literature. The suppressive and other findings need additional theoretical mechanisms and these theoretical mechanisms need to have established relationships to sonication parameters.

Original languageEnglish (US)
Article number872639
JournalFrontiers in Human Neuroscience
StatePublished - Apr 25 2022


  • focused ultrasound stimulation
  • low intensity focused ultrasound
  • neuromodulation
  • non-invasive brain stimulation
  • transcranial focused ultrasound

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Behavioral Neuroscience


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