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Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound

Wonhye Lee, Yong An Chung, Yujin Jung, In-Uk Song, Seung-Schik Yoo

BMC Neuroscience 2016, 17 · 10.1186/s12868-016-0303-6

human healthyhealthybehaviour

Abstract

Background Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans-the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Results Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand-vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject's mental/physical status. Conclusions The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

Abstract via europepmc.

Specieshuman
Subjects10 participants
Sessions per subjectnot reported
Randomisedyes
Blindingdouble
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesianot applicable
Readoutsbehaviourself-reported type/location of tactile sensations; touch-sensor tap response indicating sensation timing
Direction of effectexcitatoryFUS to SI, SII, or SI+SII simultaneously elicited tactile sensations (e.g. tingling, weak electrical current, numbness) from the hand/arm contralateral to sonication in most subjects, with no sensations reported during sham; stimulation of specific SII sub-regions did not reliably elicit the corresponding sensation-specific percept, indicating an excitatory but not finely spatially-selective effect.
Adverse eventsnone observedNeurological examination and MMSE before/after sonication and at follow-up (same day, 2 weeks, 4 weeks) showed no abnormal findings; telephone follow-up at 8 weeks reported no discomfort or mental/physical changes. Estimated in-situ intensity (7.0-8.8 W/cm2 Isppa, 3.5-4.4 W/cm2 Ispta) was slightly above the IEC 60601 part 2 Ispta limit of 3 W/cm2 but below intensities (up to 13.4 W/cm2 Isppa in situ) previously found not to cause microscopic brain damage in sheep; estimated temperature rise was 0.0092 degC.

Exposures

Exposure 1: SI_FUS: stimulation of primary somatosensory cortex alone

Target: primary somatosensory cortex — “primary somatosensory area (SI) of the hand
Device: Ultran · The Ultran Group Ltd · single-element FUS transducer, 210 kHz, 30 mm outer diameter, 25 mm focal distance

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)210✓✓
Pulse duration (ms)1✓✓
Pulse repetition frequency (Hz)500✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)35✓✓
Free-field Ispta (W/cm²)17.5✓✓
In-situ estimatederatingmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)7, 8.8swept✓✓
In-situ Ispta (W/cm²)3.5, 4.4swept✓✓
Protocol, in the paper’s words

FUS procedures were divided into multiple sessions: (1) SI alone (SI_FUS), (2) four sub-regions of SII (SII_FUS), (3) simultaneous SI and SII (SI/SII_FUS), and (4) sham (Sham_FUS, same setup without sonication); condition order was randomized and balanced across subjects. Sonication was administered 20 times per session/sub-region. Participants tapped a touch sensor to report sensation timing and verbally reported location/type of sensation after each condition; both subject and operator were blinded to the nature of the sonication.

Exposure 2: SII_FUS: stimulation of secondary somatosensory cortex sub-regions (vibrotactile, pressure, warmth, coolness)

Target: secondary somatosensory cortex — “secondary somatosensory area (SII)
Device: Ultran · The Ultran Group Ltd · single-element FUS transducer, 210 kHz, 30 mm outer diameter, 25 mm focal distance

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)210✓✓
Pulse duration (ms)1✓✓
Pulse repetition frequency (Hz)500✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)35✓✓
Free-field Ispta (W/cm²)17.5✓✓
In-situ estimatederatingmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)7, 8.8swept✓✓
In-situ Ispta (W/cm²)3.5, 4.4swept✓✓
Protocol, in the paper’s words

FUS procedures were divided into multiple sessions: (1) SI alone (SI_FUS), (2) four sub-regions of SII corresponding to vibrotactile, pressure, warmth and coolness representations (SII_FUS), (3) simultaneous SI and SII (SI/SII_FUS), and (4) sham (Sham_FUS, same setup without sonication); condition order was randomized and balanced across subjects. Sonication was administered 20 times per session/sub-region. Participants tapped a touch sensor to report sensation timing and verbally reported location/type of sensation after each condition; both subject and operator were blinded to the nature of the sonication.

Flags from extraction

  • n_sessions_per_subjectThe FUS procedure comprised multiple within-day condition blocks per subject (SI alone; four SII sub-regions; four SI/SII sub-regions; sham), each given 20 times, but the paper does not state a single 'number of sessions per subject'; left not_reported rather than computed by counting condition blocks.
  • exposures[0].in_situ.isppa_w_cm2In-situ intensity is an estimate (not per-subject simulation or measurement) based on a previously reported average transcranial transmission rate of 20-25%, given as a range (7.0-8.8 W/cm2 Isppa); the midpoint (7.9) is recorded per schema convention and the quote carries the full range.
  • exposures[*].targetIn the SI/SII_FUS condition both SI and SII were sonicated simultaneously with two independent transducers using the same parameters; this combined condition is captured in protocol_description under both the SI and SII exposures rather than as a separate exposure, since the target/frequency pairs are unchanged.