Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity

Huang, Stanley; Fisher, Joan M.; Ye, Meijun; Kim, Yun-Soung; Ma, Rui; Nabili, Marjan; Krauthamer, Victor; Myers, Matthew R.; Coleman, Todd P.; Welle, Cristin G.

doi:10.1109/tbme.2017.2713647

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…One additional limitation is that data from the ipsilateral and contralateral hemispheres were collected in different cohorts. Future work can include recordings from dual-hemisphere µECoG arrays, or through the use of dual hemisphere epidermal arrays to eliminate surgical confounds 10 .…”

Section: Discussionmentioning

confidence: 99%

“…In acoustic neuromodulation, transient functional changes in the nervous system occur, enabling the transient inhibition or excitation of electrical signals (reviewed in 7 ). These functional changes usually occur during the sonication, but can outlast the sonication by several minutes to 2 hours depending on the intensity and duty cycle 1–3,8–10 . While no evidence of long-term neural changes has been reported for current clinical neuromodulation procedures, the envelope outside of which long-term deficits occur has not been established.…”

Section: Introductionmentioning

confidence: 99%

“…The characteristics of the ultrasound pulse train do not reflect any current clinical ultrasound procedure. Rather, the ultrasound protocol was chosen to have a high likelihood of generating neurological deficits, based upon previous reports 8,10,12 , not be accompanied by gross thermal damage or destruction due to cavitation. Identifying this critical threshold, where conventional gross histology methods may fail to detect damage, but neurological deficits persist, is critical given the growing exploration of novel therapeutic modalities and protocols for ultrasound therapies 13–19 .…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Solarana

Rafi

et al. 2019

Sci Rep

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Exposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage. In this study, we assessed the neuroinflammatory response, behavioral effects, and brain micro-electrocorticographic (µECoG) signals in mice following exposure to a train of transcranial pulses above normal clinical parameters. We found that the HIFU exposure induced a mild regional neuroinflammation not localized to the primary focal site, and impaired locomotor and exploratory behavior for up to 1 month post-exposure. In addition, low frequency (δ) and high frequency (β, γ) oscillations recorded by ECoG were altered at acute and chronic time points following HIFU application. ECoG signal changes on the hemisphere ipsilateral to HIFU exposure are of greater magnitude than the contralateral hemisphere, and persist for up to three months. These results are useful for describing the upper limit of transcranial ultrasound protocols, and the neurological sequelae of injury induced by high-intensity stress waves.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Solarana

Rafi

et al. 2019

Sci Rep

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“…Although epidural measurements of SSEPs are invasive, we have previously compared the effects of injury on SSEPs measured both epidurally and epidermally 23 , 24 . In mouse experiments, SSEP waveforms measured using both approaches differ only in signal-to-noise ratio, which is roughly an order of magnitude higher when measured epidurally.…”

Section: Methodsmentioning

confidence: 99%

Alterations in neurovascular coupling following acute traumatic brain injury

et al. 2017

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Following acute traumatic brain injury (TBI), timely transport to a hospital can significantly improve the prognosis for recovery. There is, however, a dearth of quantitative biomarkers for brain injury that can be rapidly acquired and interpreted in active, field environments in which TBIs are frequently incurred. We explored potential functional indicators for TBI that can be noninvasively obtained through portable detection modalities, namely optical and electrophysiological approaches. By combining diffuse correlation spectroscopy with colocalized electrophysiological measurements in a mouse model of TBI, we observed concomitant alterations in sensory-evoked cerebral blood flow (CBF) and electrical potentials following controlled cortical impact. Injury acutely reduced the peak amplitude of both electrophysiological and CBF responses, which mostly recovered to baseline values within 30 min, and intertrial variability for these parameters was also acutely altered. Notably, the postinjury dynamics of the CBF overshoot and undershoot amplitudes differed significantly; whereas the amplitude of the initial peak of stimulus-evoked CBF recovered relatively rapidly, the ensuing undershoot did not appear to recover within 30 min of injury. Additionally, acute injury induced apparent low-frequency oscillatory behavior in CBF ([Formula: see text]). Histological assessment indicated that these physiological alterations were not associated with any major, persisting anatomical changes. Several time-domain features of the blood flow and electrophysiological responses showed strong correlations in recovery kinetics. Overall, our results reveal an array of stereotyped, injury-induced alterations in electrophysiological and hemodynamic responses that can be rapidly obtained using a combination of portable detection techniques.

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“…Additionally the magnitude of spatiotemporal aspects of the electrical potentials recorded at the scalp are heavily influenced by axonal orientation and contributions from subcortical sensory relay. Recently, Yu et al utilized electrophysiological source localization in rats to model the lateral profile of FUS-evoked activity (Yu et al, 2016), and Huang and Fisher et al (2017) used epidermal electrode arrays to observe changes in somatosensory evoked potentials at the acoustic focus. As an alternative approach, Tufail et al characterized post-mortem c-fos expression, which can indicate electrical activity, in brains of animals exposed to low-intensity FUS shortly before being sacrificed (Tufail et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responsesin vivo

Fisher

Gumenchuk

2017

Preprint

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The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Compared with other noninvasive neuromodulation approaches, key technical advantages include high lateral resolution of stimulation and deep penetration depth. However, empirically observed effects in vivo are diverse; for example, variations in sonication location and waveform can alternatively elicit putatively inhibitory or excitatory effects. At a fundamental level, it is unclear how FUS alters the function of neural circuits at the site of sonication. To address this knowledge gap, we developed an approach to optically interrogate the spatiotemporal patterns of neural activity in the cortex directly at the acoustic focus, thereby offering a glimpse into the local effects of FUS on distributed populations of neurons in vivo. Our experiments probed electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic GCaMP6f mice, monitored associated Ca 2+ responses. Our results directly demonstrate that low-intensity FUS adjusts both the kinetics and spatial patterns of sensory receptive fields at the acoustic focus in vivo. Although our experimental configuration limits interpretation to population activity, the use of VSDs ensures that the detected alterations reflect activity in cortical neurons, unobscured by signals in subcortical or laterally distant cortical regions. More generally, this optical measurement paradigm can be implemented to observe FUS-induced alterations in cortical representation with higher lateral resolution spatial versatility than is practical through more conventional electrodebased measurements. Our findings suggest that reports of FUS-induced sensory modulation in human studies may partly reflect alterations cortical representation and reactivity.

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Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity

Abstract: 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.

Cited by 9 publications

References 37 publications

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Alterations in neurovascular coupling following acute traumatic brain injury

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responsesin vivo

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