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Safety and Feasibility of Low-Intensity Transcranial Focused Ultrasound Targeting the Anterior Thalamus

Glaucia Aline Nunes, Josimar Reis Ortiz, Claudia Mingrone, Debora Arnaut, Hélder Picarelli, Ricardo Ferrareto Iglesio, Ricardo de Carvalho Nogueira, Juliana da Silva Simões, Pedro Nascimento Martins, Jose Renato Felix Bauab, Renata Montes Garcia Barbosa, Gabriel Taricani Kubota, Rubens Gisbert Cury, Manoel Jacobsen Teixeira, Marco Antônio Marcolin

The Journal of ECT 2026 · 10.1097/yct.0000000000001298

human patientchronic painclinical scale

Abstract

Low-intensity transcranial focused ultrasound (tFUS) is a novel noninvasive neuromodulation technique capable of reaching deep brain structures with high spatial precision. The anterior thalamus, a key relay in pain processing, is a promising target for modulating central pain networks. In this context, this study aims to assess the safety, feasibility, and preliminary effects of anterior thalamic low-intensity tFUS in patients with chronic Central Neuropathic Pain (CNP). In this prospective, open-label, single-arm pilot study, 5 adults with refractory central neuropathic pain underwent neuronavigated low-intensity transcranial focused ultrasound targeting the anterior thalamus contralateral to the pain-affected region. Each session consisted of two 10-minute stimulation blocks separated by 20 minutes. Pain intensity was assessed using the visual analog scale at baseline, immediately poststimulation, and also after 4 hours, 24 hours and 10 days after the intervention. Secondary outcomes included the Brief Pain Inventory, McGill Pain Questionnaire, Douleur Neuropatique 4, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Patient Global Impression of Change and Clinical Global Impression of Change scale. The procedure demonstrated feasible with no serious adverse events. One participant experienced mild transient neck discomfort. No statistically significant improvements were observed in pain intensity or secondary outcomes at any time point compared with baseline. Overall, anterior thalamic low-intensity tFUS presented safe and feasible for patients with CNP but did not yield significant short-term analgesic effects. These findings support further controlled clinical trials with larger samples, optimized stimulation parameters and repeated sessions to better evaluate the therapeutic potential of low-intensity tFUS for chronic CNP.

Abstract via europepmc.

Specieshuman
Subjects5 participants
Sessions per subject2
Randomisedno
Blindingnone
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsclinical scaleVisual Analog Scale (VAS); Brief Pain Inventory (BPI); McGill Pain Questionnaire; Douleur Neuropathique 4 (DN4); Hamilton Depression Rating Scale (HAM-D); Hamilton Anxiety Rating Scale (HAM-A); Patient Global Impression of Change (PGI-C); Clinical Global Impression of Change (CGI-C)
Direction of effectno effectNo statistically significant differences in VAS pain scores or secondary outcomes (BPI, McGill, DN4, HAM-D, HAM-A, PGI-C, CGI-C) were observed at any post-stimulation time point (immediate, 4h, 24h, 10 days) compared with baseline.
Adverse eventsobservedOne participant experienced mild transient neck discomfort; no serious adverse events or neurological complications were reported.

Exposures

Exposure 1: anterior thalamus tFUS, contralateral to pain side

Target: anterior thalamic nucleus — “anterior thalamus
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS PRO (64 mm transducer)

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)5✓✓
Pulse repetition frequency (Hz)10✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓
Sonication duration (s)30✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Isppa, domain unspecified (W/cm²)30✓✓
Protocol, in the paper’s words

Each tFUS session consisted of 10 cycles, with each comprising 30 s of sonication followed by a 30-second interval, with a total 10-minute duration. Participants underwent 2 such sessions, with a 20-minute interval in between.

Flags from extraction

  • unspecified_domain.isppa_w_cm2Paper states maximum ISPPA=30 W/cm2 without specifying whether this is a free-field or in-situ/derated value.
  • auditory_controlPaper does not mention any auditory-confound control (masking sound, sham tone, etc.).
  • adverse_eventsOnly a single mild transient neck-discomfort event was reported (no serious adverse events); classified as 'observed' rather than 'none_observed'.