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Functional Ultrasound Imaging Following Supra-physiologic 10,000 Hz Stimulation of the Medial Septal Nucleus

Friday, May 3, 2024

    Presenting Author(s)

  • Jack Lo, MBBS

    Resident
    Department of Neurosurgery, USC Keck Medical Center
    Singapore, SG

    • Co-Author(s)

  • Kevin Wu, BS

    Medical Student
    USC Keck School of Medicine
    Los Angeles, CA, US

  • KA

    Kofi Agyeman, MS

    PhD Candidate
    Bioengineering, University of California, Riverside, Riverside, CA, USA, United States

  • MB

    Matthew Bergosh, BS

    Research Assistant
    Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, United States

  • GB

    Grady Briggs, MD

    Resident
    Department of Neurosurgery, USC Keck Medical Center, United States

  • Wooseong Choi, BS (he/him/his)

    PhD Candidate
    Department of Neurosurgery, USC Keck Medical Center
    Los Angeles, California, United States

  • RC

    Rebecca Chow, n/a

    Research Assistant
    University of Southern California, Los Angeles, Ca, USA, United States

  • LC

    Lindsey M. Crown, PhD

    Post-Doctoral Fellow
    Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, United States

  • Darrin J. Lee, MD PhD

    Assistant Professor
    Department of Neurosurgery, USC Keck Medical Center
    Los Angeles, California, United States

  • Charles Y. Liu, MD, PhD

    Professor of Clinical Neurological Surgery
    Keck School of Medicine at USC
    Los Angeles, California, United States

  • AP

    Avinash Pandit, n/a

    Research Assistant
    University of Southern California, Los Angeles, Ca, USA, United States

  • AQ

    Aafreen Qureshi, n/a

    Research Assistant
    University of Southern California, Los Angeles, Ca, USA, United States

  • CV

    Christopolous Vasileios, PhD

    Assistant Professor
    UC Riverside, United States

  • NZ

    Nancy Zepeda, BS

    Research Assistant
    Department of Neurosurgery, USC Keck Medical Center
    Los Angeles, California, United States

Introduction: Conventional deep brain stimulation for Parkinson’s disease employs gamma range (~130-180Hz) stimulation, and higher frequencies are believed to increase adverse effect risk with no additional benefit. Evidence exists to suggest a comparable level of motor improvement can be achieved with a supra-physiologic frequency of 10kHz. In this study, we applied 10kHz stimulation on the medial septal nucleus (MSN) in mice and assessed neuronal activity with functional ultrasound imaging (fUSI), a recently developed imaging modality with greater spatial resolution (~100uM2) than fMRI and high sensitivity to slow blood flow (>1mm/s).

Methods: Fourteen male C57BL/6 mice were stereotactically implanted with electrodes in the MSN via a frontal burr hole and partitioned into either the experimental (n=9) or control (n=5) group. fUSI recordings were then obtained contralaterally for 40-minutes: five-minute of baseline, five minutes of intervention (10kHz stimulation at 0.1mA vs. none), and thirty minutes post-stimulation. Power doppler (pD) signals were extracted from the fUS recording and changes in pD (ΔpD) were evaluated for three regions of interest (ROIs): medial prefrontal cortex (mPFC), thalamus and hippocampus.

Results: During stimulation, mean CBVs were greater in the stimulation vs. sham group in all ROIs (mPFC: -1.1 vs -2.0a.u., thalamus: -0.3 vs. -0.7a.u., hippocampus: -0.2 vs -0.3a.u., all p< 0.001). In the last five minutes of the post-stimulation period, mean CBV was greater in the thalamus (-0.7 vs -1.4a.u.), and lower in the mPFC and hippocampus (-3.5 vs -2.8a.u. and -0.9 vs -0.5a.u. respectively, all p< 0.001) in the HFS group vs. sham.

Conclusion : 10kHz stimulation of the MSN causes regional blood flow changes that may be distinct from theta and gamma stimulation, suggesting a unique activation pattern. Taken in conjunction with previous studies, MSN stimulatory effect throughout the deep brain and cortex appears to be frequency-dependent.