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Thalamic transcranial ultrasound stimulation in treatment resistant depression

Joline M. Fan, Kai Woodworth, Keith R. Murphy, Leighton Hinkley, Joshua L. Cohen, Joanne Yoshimura, Inhauck Choi, Alexandra G. Tremblay-McGaw, Joncarmen Mergenthaler, Cameron H. Good, Peter A. Pellionisz, A.Moses Lee, Tommaso Di Ianni, Leo P. Sugrue, Andrew D. Krystal

Brain Stimulation 2024, 17, 1001-1004 · 10.1016/j.brs.2024.08.006

human patientdepressionclinical scalebehaviourfmri
Specieshuman
Subjects1 participants
Sessions per subjectnot reported
Randomisednot reported
Blindingdouble
Sham / controlunfocused or detuned
Auditory controlnot reported
Readout timingboth
Anaesthesianot applicable
Readoutsclinical scale, behaviour, fmri6-item Hamilton Depression Rating Scale (HAMD-6); visual analog scale (VAS) of depression; resting-state fMRI default mode network (DMN) connectivity
Direction of effectinhibitoryANT TUS reduced VAS-depression scores over time relative to the unfocused control condition and reduced default mode network (DMN) connectivity compared to the hyperconnected baseline; VC/BNST stimulation did not significantly reduce symptom scores.
Adverse eventsnone observedThe intermittent TUS protocol was well tolerated by the participant without any adverse effects. A post-stimulation MRI scan did not reveal any structural changes, including edema or hemorrhage.

Exposures

Exposure 1: VC/BNST dynamically-steered TUS

Target: internal capsule, other — “ventral capsule (VC) / bed nucleus of stria terminalis (BNST)
Device: Attune · Attune Neurosciences, Inc. · ATTN201

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 5.2 ms (not stated by the paper)
Pulse repetition frequency (Hz)25✓✓
Duty cycle (%)13✓✓
Sonication duration (s)300✓✓
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 estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)42.2, 50.2swept✓✓
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Stimulation was bilateral, alternating between left and right lateralized regions every 15 minutes, i.e. 10 min inter pulse train interval. Eight total pulse trains (four left and four right) were performed to complete a full session; each followed by a 24-hr washout period.

Exposure 2: ANT dynamically-steered TUS

Target: anterior thalamic nucleus — “anterior nucleus of the thalamus (ANT)
Device: Attune · Attune Neurosciences, Inc. · ATTN201

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 5.2 ms (not stated by the paper)
Pulse repetition frequency (Hz)25✓✓
Duty cycle (%)13✓✓
Sonication duration (s)300✓✓
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 estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)42.2, 50.2swept✓✓
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Stimulation was bilateral, alternating between left and right lateralized regions every 15 minutes, i.e. 10 min inter pulse train interval. Eight total pulse trains (four left and four right) were performed to complete a full session; each followed by a 24-hr washout period.

Flags from extraction

  • n_subjectsSingle-subject case report.
  • sham_typeUnfocused control delivers the same acoustic energy at the array surface without a deep-brain focal pattern; does not clearly match inactive_transducer, active_control_site or sound_only, so classified as other.
  • exposures[0].targetVC and BNST were reported together as a combined 'VC/BNST' condition in the results and figures; treated as one exposure. VC mapped to internal_capsule (ventral capsule/ALIC synonym) and BNST has no matching target id, mapped to other.
  • exposures[0].in_situ.isppa_w_cm2The 42.2-50.2 W/cm2 range is reported for 'active conditions' generally (right-lateralized regions) rather than separately for each of VC/BNST vs ANT; applied to both exposures as the paper does not give per-target values.
  • n_sessions_per_subjectPaper describes an exploratory phase, serial testing of three regions over multiple days, and top-candidate vs unfocused comparison, but does not state a single total number of sessions per condition.
  • blindingPaper states resting-state fMRI was collected following 'double-blinded ANT stimulation' but does not otherwise describe the blinding scheme for the full study.