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

BackgroundTranscranial 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.ResultsUnder 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.ConclusionsThe 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.

[1]  R. Parkkola,et al.  Modulation of facial sensitivity by navigated rTMS in healthy subjects , 2009, Pain.

[2]  W. Newsome,et al.  Effective parameters for ultrasound-induced in vivo neurostimulation. , 2013, Ultrasound in medicine & biology.

[3]  Steen Moeller,et al.  Multiband multislice GE‐EPI at 7 tesla, with 16‐fold acceleration using partial parallel imaging with application to high spatial and temporal whole‐brain fMRI , 2010, Magnetic resonance in medicine.

[4]  W. O’Brien.  Ultrasound-biophysics mechanisms. , 2007, Progress in biophysics and molecular biology.

[5]  H. Matute,et al.  Reducing the illusion of control when an action is followed by an undesired outcome , 2014, Psychonomic bulletin & review.

[6]  Jong-Hwan Lee,et al.  Focused ultrasound modulates region-specific brain activity , 2011, NeuroImage.

[7]  W. Fry,et al.  Production of reversible changes in the central nervous system by ultrasound. , 1958, Science.

[8]  M. Iacoboni,et al.  Correlation between motor and phosphene thresholds: A transcranial magnetic stimulation study , 2008, Human brain mapping.

[9]  Wonhye Lee,et al.  Image-Guided Focused Ultrasound-Mediated Regional Brain Stimulation in Sheep. , 2016, Ultrasound in medicine & biology.

[10]  A. Williams,et al.  Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans , 2014, Nature Neuroscience.

[11]  Natalia Vykhodtseva,et al.  Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. , 2012, Cancer research.

[12]  Mickael Tanter,et al.  Numerical prediction of frequency dependent 3D maps of mechanical index thresholds in ultrasonic brain therapy , 2010, 2010 IEEE International Ultrasonics Symposium.

[13]  S. Yoo,et al.  Image-Guided Transcranial Focused Ultrasound Stimulates Human Primary Somatosensory Cortex , 2015, Scientific Reports.

[14]  Kirsten J. McKenzie,et al.  Multisensory distortions of the hand have differential effects on tactile perception , 2015, Experimental Brain Research.

[15]  Natalia Vykhodtseva,et al.  500‐element ultrasound phased array system for noninvasive focal surgery of the brain: A preliminary rabbit study with ex vivo human skulls , 2004, Magnetic resonance in medicine.

[16]  Mark S. George,et al.  Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation? , 2008, Brain Stimulation.

[17]  Amit P. Mulgaonkar,et al.  A review of low-intensity focused ultrasound pulsation , 2011, Brain Stimulation.

[18]  Hartwig R. Siebner,et al.  The right posterior inferior frontal gyrus contributes to phonological word decisions in the healthy brain: Evidence from dual-site TMS , 2010, Neuropsychologia.

[19]  E. Gellhorn,et al.  Influence of increased temperature on activity of the cerebral cortex. , 1949, The American journal of physiology.

[20]  Michael B. Smith,et al.  Model of local temperature changes in brain upon functional activation. , 2004, Journal of applied physiology.

[21]  Mathieu Pernot,et al.  Targeting accuracy of transcranial magnetic resonance-guided high-intensity focused ultrasound brain therapy: a fresh cadaver model. , 2013, Journal of neurosurgery.

[22]  Stephanie D. Lee,et al.  Evaluation of polyvinyl alcohol cryogel as an acoustic coupling medium for low‐intensity transcranial focused ultrasound , 2014, Int. J. Imaging Syst. Technol..

[23]  Paul B. Fitzgerald,et al.  Brain stimulation in psychiatry and its effects on cognition , 2010, Nature Reviews Neurology.

[24]  U. Pesonen,et al.  Right secondary somatosensory cortex—a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation , 2015, Pain.

[25]  Jay B. West,et al.  The distribution of target registration error in rigid-body point-based registration , 2001, IEEE Transactions on Medical Imaging.

[26]  Yusuf Tufail,et al.  Remote Excitation of Neuronal Circuits Using Low-Intensity, Low-Frequency Ultrasound , 2008, PloS one.

[27]  S. Yoo,et al.  Focused Ultrasound-mediated Non-invasive Brain Stimulation: Examination of Sonication Parameters , 2014, Brain Stimulation.

[28]  M. Tanter,et al.  Low intensity focused ultrasound modulates monkey visuomotor behavior , 2013, Current Biology.

[29]  J. Karhu,et al.  Simultaneous early processing of sensory input in human primary (SI) and secondary (SII) somatosensory cortices. , 1999, Journal of neurophysiology.

[30]  D P Salmon,et al.  The Mini-Mental State Examination in the early diagnosis of Alzheimer's disease. , 1990, Archives of neurology.

[31]  Stephanie D. Lee,et al.  Neural substrates in secondary somatosensory area for the perception of different tactile sensations , 2016, Int. J. Imaging Syst. Technol..

[32]  Patricia C. Rinaldi,et al.  Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation , 1991, Brain Research.

[33]  Jay B. West,et al.  Fiducial Point Placement and the Accuracy of Point-based, Rigid Body Registration , 2001, Neurosurgery.

[34]  A. Shmuel,et al.  Imaging brain function in humans at 7 Tesla , 2001, Magnetic resonance in medicine.

[35]  Hyungmin Kim,et al.  Image‐guided navigation of single‐element focused ultrasound transducer , 2012, Int. J. Imaging Syst. Technol..

[36]  Guy Marchal,et al.  Multimodality image registration by maximization of mutual information , 1997, IEEE Transactions on Medical Imaging.

[37]  Sarah H. Lisanby,et al.  Fundamentals of transcranial electric and magnetic stimulation dose: Definition, selection, and reporting practices , 2012, Brain Stimulation.

[38]  K. Amunts,et al.  The human parietal operculum. II. Stereotaxic maps and correlation with functional imaging results. , 2006, Cerebral cortex.

[39]  M. Fink,et al.  Influence of the pressure field distribution in transcranial ultrasonic neurostimulation. , 2013, Medical physics.

[40]  S. Tillery,et al.  Transcranial Pulsed Ultrasound Stimulates Intact Brain Circuits , 2010, Neuron.

[41]  F Mauguière,et al.  Somatosensory and pain responses to stimulation of the second somatosensory area (SII) in humans. A comparison with SI and insular responses. , 2006, Cerebral cortex.

[42]  K. Hynynen,et al.  MRI investigation of the threshold for thermally induced blood–brain barrier disruption and brain tissue damage in the rabbit brain , 2004, Magnetic resonance in medicine.

[43]  Roland Peyron,et al.  Spatial segregation of somato-sensory and pain activations in the human operculo-insular cortex , 2012, NeuroImage.

[44]  G. Miesenböck,et al.  The Optogenetic Catechism , 2009, Science.

[45]  H. Möller,et al.  Repetitive Transcranial Magnetic Stimulation , 2003, CNS drugs.

[46]  Max Wintermark,et al.  A pilot study of focused ultrasound thalamotomy for essential tremor. , 2013, The New England journal of medicine.

[47]  A. Morel,et al.  High‐intensity focused ultrasound for noninvasive functional neurosurgery , 2009, Annals of neurology.

[48]  Henrik Walter,et al.  Side Effects of Transcranial Magnetic Stimulation Biased Task Performance in a Cognitive Neuroscience Study , 2005, Brain Topography.

[49]  Sergiu Groppa,et al.  A novel dual-site transcranial magnetic stimulation paradigm to probe fast facilitatory inputs from ipsilateral dorsal premotor cortex to primary motor cortex , 2012, NeuroImage.

[50]  P. Haggard,et al.  Transcranial magnetic stimulation over human secondary somatosensory cortex disrupts perception of pain intensity , 2013, Cortex.

[51]  Karl J. Friston,et al.  Dynamic causal modeling of touch-evoked potentials in the rubber hand illusion , 2016, NeuroImage.

[52]  F Dunn,et al.  Ultrasonic absorption and attenuation in mammalian tissues. , 1979, Ultrasound in medicine & biology.

[53]  Á. Pascual-Leone,et al.  Technology Insight: noninvasive brain stimulation in neurology—perspectives on the therapeutic potential of rTMS and tDCS , 2007, Nature Clinical Practice Neurology.

[54]  S. Yoo,et al.  Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound , 2015, Neuroreport.

[55]  A Villringer,et al.  Somatotopic organization of human secondary somatosensory cortex. , 2001, Cerebral cortex.

[56]  Á. Pascual-Leone,et al.  Noninvasive human brain stimulation. , 2007, Annual review of biomedical engineering.

[57]  G. Aston-Jones,et al.  Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) , 2010, Neuropsychopharmacology.

[58]  Francis A Duck,et al.  Medical and non-medical protection standards for ultrasound and infrasound. , 2007, Progress in biophysics and molecular biology.