Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report
Thomas S. Riis, Daniel A. Feldman, Lily C. Vonesh, Jefferson R. Brown, Daniela Solzbacher, Jan Kubanek, Brian J. Mickey
Journal of Medical Case Reports 2023, 17 · 10.1186/s13256-023-04194-4
Abstract
Background Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits. Here we describe an application of this tool to an individual with treatment-resistant depression. Case presentation A 30-year-old Caucasian woman with severe treatment-resistant non-psychotic depression was recruited into a clinical study approved by the Institutional Review Board of the University of Utah. The patient had a history of electroconvulsive therapy with full remission but without sustained benefit. Magnetic resonance imaging was used to coregister the ultrasound device to the subject's brain anatomy and to evaluate neural responses to stimulation. Brief, 30-millisecond pulses of low-intensity ultrasound delivered into the subcallosal cingulate cortex target every 4 seconds caused a robust decrease in functional magnetic resonance imaging blood-oxygen-level-dependent activity within the target. Following repeated stimulation of three anterior cingulate targets, the patient's depressive symptoms resolved within 24 hours of the stimulation. The patient remained in remission for at least 44 days afterwards. Conclusions This case illustrates the potential for ultrasonic neuromodulation to precisely engage deep neural circuits and to trigger a durable therapeutic reset of those circuits. Trial registration ClinicalTrials.gov, NCT05301036. Registered 29 March 2022, https://clinicaltrials.gov/ct2/show/NCT05301036.
Abstract via europepmc.
Exposures
Exposure 1: Ultrasound stimulation of three SCC-associated cingulate targets (posterior SCC, anterior SCC, pregenual cingulate)
Target: subgenual anterior cingulate cortex, pregenual anterior cingulate cortex — “posterior subcallosal cingulate cortex (SCC), anterior SCC, and pregenual cingulate”
Device: custom-built · Diadem
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 0.8 | ✓✓✓ |
| Sonication duration (s) | 20, 180swept | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 1,000 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Each target was sonicated with a 650 kHz continuous wave for 30-millisecond ON periods followed by 4-second OFF periods (0.8% duty) for an average duration of 2 minutes (range 20-180 seconds). Each target was sonicated ten times, with randomized order between the three sites, for a total of 30 stimulation epochs spanning 64 minutes of active stimulation within an overall 2-hour stimulation session. A separate unfocused (plane-wave) control stimulus with the same waveform and pressure amplitude was also delivered to control for generic ultrasound artifacts.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Paper states 30 ms ON periods followed by 4 s OFF periods but does not label a pulse repetition frequency; not computed here.exposures— Three anatomically distinct cingulate sub-targets (posterior SCC, anterior SCC, pregenual cingulate) shared identical frequency and timing parameters and were combined into a single exposure entry rather than split three ways.sham_type— Control stimulus was an unfocused (plane-wave) ultrasound of the same waveform/pressure, which does not map cleanly onto the closed sham_type vocabulary; classified as other.in_situ.method— Peak pressure at target is described as 'estimated' via Diadem's individualized measurement-based compensation for skull/hair attenuation; not explicitly labelled simulation, derating, or measurement in the text, classified as measurement given the through-transmit calibration described.