Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity

Objective: We aim to demonstrate the in vivo capability of a wearable sensor technology to detect localized perturbations of sensory-evoked brain activity. Methods: Cortical somatosensory evoked potentials (SSEPs) were recorded in mice via wearable, flexible epidermal electrode arrays. We then utilized the sensors to explore the effects of transcranial focused ultrasound, which noninvasively induced neural perturbation. SSEPs recorded with flexible epidermal sensors were quantified and benchmarked against those recorded with invasive epidural electrodes. Results: We found that cortical SSEPs recorded by flexible epidermal sensors were stimulus frequency dependent. Immediately following controlled, focal ultrasound perturbation, the sensors detected significant SSEP modulation, which consisted of dynamic amplitude decreases and altered stimulus-frequency dependence. These modifications were also dependent on the ultrasound perturbation dosage. The effects were consistent with those recorded with invasive electrodes, albeit with roughly one order of magnitude lower signal-to-noise ratio. Conclusion: We found that flexible epidermal sensors reported multiple SSEP parameters that were sensitive to focused ultrasound. This work therefore 1) establishes that epidermal electrodes are appropriate for monitoring the integrity of major CNS functionalities through SSEP; and 2) leveraged this technology to explore ultrasound-induced neuromodulation. The sensor technology is well suited for this application because the sensor electrical properties are uninfluenced by direct exposure to ultrasound irradiation. Significance: The sensors and experimental paradigm we present involve standard, safe clinical neurological assessment methods and are thus applicable to a wide range of future translational studies in humans with any manner of health condition.

[1]  M. Silvestrini,et al.  Early EEG contributes to multimodal outcome prediction of postanoxic coma. , 2016, Neurology.

[2]  Yingying Su,et al.  Somatosensory and Brainstem Auditory Evoked Potentials Assessed between 4 and 7 Days after Severe Stroke Onset Predict Unfavorable Outcome , 2015, BioMed research international.

[3]  James J. S. Norton,et al.  Soft, curved electrode systems capable of integration on the auricle as a persistent brain–computer interface , 2015, Proceedings of the National Academy of Sciences.

[4]  M. Myers,et al.  Application of high-intensity focused ultrasound to the study of mild traumatic brain injury. , 2014, Ultrasound in medicine & biology.

[5]  J. Desmedt,et al.  Clinical uses of cerebral, brainstem, and spinal somatosensory evoked potentials , 1980 .

[6]  Vedran Deletis,et al.  Intraoperative neurophysiological monitoring of the spinal cord during spinal cord and spine surgery: A review focus on the corticospinal tracts , 2008, Clinical Neurophysiology.

[7]  P. Kaplan,et al.  Clinical Applications for EPs in the ICU , 2015, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[8]  C. Ploner,et al.  Amplitudes of SSEP and outcome in cardiac arrest survivors , 2015, Neurology.

[9]  F. Deriu,et al.  Comparison of brainstem reflex recordings and evoked potentials with clinical and MRI data to assess brainstem dysfunction in multiple sclerosis: a short-term follow-up , 2016, Neurological Sciences.

[10]  T. Yamada,et al.  The effects of stimulus rates upon median, ulnar and radial nerve somatosensory evoked potentials. , 1994, Electroencephalography and clinical neurophysiology.

[11]  R P Lesser,et al.  Cortical somatosensory evoked potentials in response to hand stimulation. , 1983, Journal of neurosurgery.

[12]  W. Tyler Noninvasive Neuromodulation with Ultrasound? A Continuum Mechanics Hypothesis , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[13]  James J. S. Norton,et al.  Materials and Optimized Designs for Human‐Machine Interfaces Via Epidermal Electronics , 2013, Advanced materials.

[14]  M R Nuwer,et al.  Fundamentals of evoked potentials and common clinical applications today. , 1998, Electroencephalography and clinical neurophysiology.

[15]  Jeonghyun Kim,et al.  An Epidermal Stimulation and Sensing Platform for Sensorimotor Prosthetic Control, Management of Lower Back Exertion, and Electrical Muscle Activation , 2016, Advanced materials.

[16]  P. M. Rossini,et al.  Recommendations for the clinical use of somatosensory-evoked potentials , 2008, Clinical Neurophysiology.

[17]  L. Zhai,et al.  Measurement of high intensity focused ultrasound fields by a fiber optic probe hydrophone. , 2006, The Journal of the Acoustical Society of America.

[18]  Yonggang Huang,et al.  Silicon nanomembranes for fingertip electronics , 2012, Nanotechnology.

[19]  Yingying Su,et al.  Predicting comatose patients with acute stroke outcome using middle-latency somatosensory evoked potentials , 2011, Clinical Neurophysiology.

[20]  A. Ngai,et al.  Frequency-dependent changes in cerebral blood flow and evoked potentials during somatosensory stimulation in the rat , 1999, Brain Research.

[21]  Matthew R. Myers,et al.  Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials , 2016, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[22]  J. Detre,et al.  Spatiotemporal Quantification of Cerebral Blood Flow during Functional Activation in Rat Somatosensory Cortex using Laser-Speckle Flowmetry , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  Guideline 9D: Guidelines on Short-Latency Somatosensory Evoked Potentials , 2006, American journal of electroneurodiagnostic technology.

[24]  Allan H. Ropper,et al.  Evoked potentials in clinical medicine (second of two parts). , 1982 .

[25]  R. Thatcher,et al.  An EEG severity index of traumatic brain injury. , 2001, The Journal of neuropsychiatry and clinical neurosciences.

[26]  J. Binnekade,et al.  Predictive value of neurological examination for early cortical responses to somatosensory evoked potentials in patients with postanoxic coma , 2011, Journal of Neurology.

[27]  Dae-Hyeong Kim,et al.  Multifunctional wearable devices for diagnosis and therapy of movement disorders. , 2014, Nature nanotechnology.

[28]  J C Mazziotta,et al.  Effects of stimulus rate on regional cerebral blood flow after median nerve stimulation. , 1995, Brain : a journal of neurology.

[29]  M. Myers,et al.  Animal models for the study of military-related, blast-induced traumatic brain injury , 2010, 2010 Biomedical Sciences and Engineering Conference.

[30]  Stephen M. Mann,et al.  Surgeon-driven neurophysiologic monitoring in a spinal surgery population. , 2016, Journal of spine surgery.

[31]  K. Johnston,et al.  Upper-limb somatosensory evoked potential monitoring in lumbosacral spine surgery: a prognostic marker for position-related ulnar nerve injury. , 2009, The spine journal : official journal of the North American Spine Society.

[32]  Pierre Maquet,et al.  Multimodal evoked potentials for functional quantification and prognosis in multiple sclerosis , 2016, BMC Neurology.

[33]  James J. Choi,et al.  Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. , 2007, Ultrasound in medicine & biology.

[34]  Raeed H. Chowdhury,et al.  Epidermal Electronics , 2011, Science.

[35]  Todd P. Coleman,et al.  Scalable Microfabrication Procedures for Adhesive-Integrated Flexible and Stretchable Electronic Sensors , 2015, Sensors.

[36]  Bin He,et al.  Electrophysiological Source Imaging of Brain Networks Perturbed by Low-Intensity Transcranial Focused Ultrasound , 2016, IEEE Transactions on Biomedical Engineering.

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

[38]  Gabriel Curio,et al.  Cortical somatosensory evoked high-frequency (600Hz) oscillations predict absence of severe hypoxic encephalopathy after resuscitation , 2016, Clinical Neurophysiology.