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Brainwaves meet soundwaves: ultrasound stimulation for treating major depressive disorder by targeting the subcallosal cingulate cortex

Neuropsychopharmacology (2025)Cite this article

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Major Depressive Disorder (MDD) remains a leading cause of disability around the world. While pharmacological and psychotherapeutic interventions are widely used, nearly half of the patients fail to respond to these standard treatments [1], leaving a significant number of individuals with what is known as treatment resistant depression (TRD).

In recent years, brain stimulation has emerged as a promising approach to directly modulate brain regions involved in depression. One such region is the subcallosal cingulate cortex (SCC), a limbic structure located beneath the corpus callosum that shows hyperactivity in individuals with depression [2]. Initial efforts using deep brain stimulation (DBS) targeting the SCC showed promising results [3]. However, invasive nature of DBS limits its widespread clinical use. Non-invasive alternatives like Transcranial Magnetic Stimulation (TMS) have since been developed and are now FDA approved for treating various neuropsychiatric disorders, including MDD [4]. That said, TMS primarily targets superficial cortical areas and can only indirectly modulate deep brain structures like the SCC, underscoring the need for better alternatives.

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Fig. 1: Controlled ultrasound stimulation of subcallosal cingulate cortex with RTT approach.

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Author notes

  1. Desmond J. Oathes

    Present address: Center for Brain Imaging and Stimulation, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Authors and Affiliations

  1. Center for Brain Imaging and Stimulation, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ahsan Khan

  2. Center for Neuromodulation in Depression and Stress, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ahsan Khan & Desmond J. Oathes

  3. Academy of Wellness and Human Development, Faculty of Arts and Social Sciences, Hong Kong Baptist University, Hong Kong, China

    Ahsan Khan

  4. Penn Brain Science, Translation, Innovation, and Modulation Center, University of Pennsylvania, Philadelphia, PA, USA

    Desmond J. Oathes

  5. Departments of Neuroscience, Bioengineering, Neurology and Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Desmond J. Oathes

Authors
  1. Ahsan Khan
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  2. Desmond J. Oathes
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AK and DJO wrote the paper.

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Correspondence to Desmond J. Oathes.

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Khan, A., Oathes, D.J. Brainwaves meet soundwaves: ultrasound stimulation for treating major depressive disorder by targeting the subcallosal cingulate cortex. Neuropsychopharmacol. (2025). https://doi.org/10.1038/s41386-025-02194-0

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  • DOI: https://doi.org/10.1038/s41386-025-02194-0

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