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BACKGROUND: Severe forms of depression have been linked to excessive subcallosal cingulate cortex (SCC) ac- tivity. Stimulation of the SCC with surgically implanted electrodes can alleviate depression, but current noninvasive techniques cannot directly and selectively modulate deep targets. We developed a new noninvasive neuromodulation approach that can deliver low-intensity focused ultrasonic waves to the SCC. METHODS: Twenty-two individuals with treatment-resistant depression participated in a randomized, double-blind, sham-controlled study. Ultrasonic stimulation was delivered to the bilateral SCC during concurrent functional magnetic resonance imaging to quantify target engagement. Mood state was measured with the Sadness subscale of the Positive and Negative Affect Schedule before and after 40 minutes of real or sham SCC stimulation. Change in depression severity was measured with the 6-item Hamilton Depression Rating Scale at 24 hours and 7 days. RESULTS: Functional magnetic resonance imaging demonstrated a target-speci c decrease in SCC activity during stimulation (p = .028, n = 16). In 7 of 16 participants, SCC neuromodulation was detectable at the individual participant level with a single 10-minute scan (p , .05, small-volume correction). Mood and depression scores improved more with real than with sham stimulation. In the per-protocol sample (n = 19), real stimulation was superior to sham for 6-item Hamilton Depression Rating Scale scores at 24 hours and for Sadness scores (both p , .05, d . 1). Nonsigni cant trends were found in the intent-to-treat sample. CONCLUSIONS: This small pilot study indicates that ultrasonic stimulation modulates SCC activity and can rapidly reduce depressive symptoms. The capability to noninvasively and selectively target deep brain areas creates new possibilities for the future development of circuit-directed therapeutics and for the analysis of deep-brain circuit function in humans.
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A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans
Abstract Advances in technologies that can record and stimulate deep brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and restricted full-duplex bidirectional capability. In this study, we developed a wearable bidirectional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans and, consequently, bridge decades of neuroscientific findings across species.
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- Award ID(s):
- 2124252
- PAR ID:
- 10451343
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Date Published:
- Journal Name:
- Nature Neuroscience
- ISSN:
- 1097-6256
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41593-023-01260-4
