Background: Low-intensity transcranial focused ultrasound stimulation is a promising candidate for noninvasive brain stimulation and accurate targeting of brain circuits because of its focusing capability and long penetration depth. However, achieving a sufficiently high spatial resolution to target small animal sub-regions is still challenging, especially in the axial direction. Objective: To achieve high axial resolution, we designed a dual-crossed transducer system that achieved high spatial resolution in the axial direction without complex microfabrication, beamforming circuitry, and signal processing. Methods: High axial resolution was achieved by crossing two ultrasound beams of commercially available piezoelectric curved transducers at the focal length of each transducer. After implementation of the fixture for the dual-crossed transducer system, three sets of in vivo animal experiments were conducted to demonstrate high target specificity of ultrasound neuromodulation using the dual-crossed transducer system (n ¼ 38). Results: The full-width at half maximum (FWHM) focal volume of our dual-crossed transducer system was under 0.52 mm 3 . We report a focal diameter in both lateral and axial directions of 1 mm. To demonstrate successful in vivo brain stimulation of wild-type mice, we observed the movement of the forepaws. In addition, we targeted the habenula and verified the high spatial specificity of our dualcrossed transducer system. Conclusions: Our results demonstrate the ability of the dual-crossed transducer system to target highly specific regions of mice brains using ultrasound stimulation. The proposed system is a valuable tool to study the complex neurological circuitry of the brain noninvasively.
There is an increasing interest in developing next-generation wearable ultrasound patch systems because of their wide range of applications, such as home healthcare systems and continuous monitoring systems for physiological conditions. A wearable ultrasound patch system requires a stable interface to the skin, an ultrasound coupling medium, a flexible transducer array, and miniaturized operating circuitries. In this study, we proposed a patch composed of calcium (Ca)-modified silk, which serves as both a stable interface and a coupling medium for ultrasound transducer arrays. The Ca-modified silk patch provided not only a stable and conformal interface between the epidermal ultrasound transducer and human skin with high adhesion but also offered acoustic impedance close to that of human skin. The Ca-modified silk patch was flexible and stretchable (∼400% strain) and could be attached to various materials. In addition, because the acoustic impedance of the Ca-modified silk patch was 2.15 MRayl, which was similar to that of human skin (1.99 MRayl), the ultrasound transmission loss of the proposed patch was relatively low (∼0.002 dB). We also verified the use of the Ca-modified silk patch in various ultrasound applications, including ultrasound imaging, ultrasound heating, and transcranial ultrasound stimulation for neuromodulation. The comparable performance of the Ca-modified patch to that of a commercial ultrasound gel and its durability against various environmental conditions confirmed that the Ca-modified silk patch could be a promising candidate as a coupling medium for next-generation ultrasound patch systems.
a specific region of the brain through various physical means, including electrical, chemical, optical, and acoustic, have been proposed to investigate neuronal circuits. [8][9][10][11][12] Furthermore, since neurons relay information to downstream neurons through either electrical or chemical synaptic transmission, real-time monitoring of neurotransmitters in the extracellular space of the brain offers additional insight to that observed from the electrophysiological activities. Thus, recently, multimodal neural probes that perform both electrical recording and neurotransmitter detection in the extracellular environment have also been proposed. [13][14][15] However, it is still a challenge to design a multimodal neural probe that detects both neurotransmitters and neural signals at a small form factor. For a multimodal neural probe, while a high-density neural recording and a high electrochemical sensitivity are preferred, a high channel count and sensitivity require a larger shank area. For example, the width of the probe scales linearly with the number of microelectrodes due to the signal lines. Similarly, for electrochemical detection, a larger working electrode (WE) on the shank is also required to achieve high sensitivity. Moreover, to achieve a reliable electrochemical analysis, two electrodes additional to the WE are required to form a three-electrode system. [16] However, because the shank dimension is directly related to the acute neural tissue damage during the insertion, it is important to design a shank with a small dimension. This clear trade-off between the probe dimension (i.e., tissue damage) and performance (i.e., channel counts and high sensitivity) is a major challenge in implementing a multimodal neural probe at a small form factor.To overcome this trade-off, several methods such as multilayer metal interconnect, [17] e-beam photolithography, [18] and dual-sided micropatterning [19,20] have been recently proposed to achieve high density without increasing the dimension of the polymer neural probes. Through these efforts, neural probe arrays with 16-channel SU-8, 32-channel polyimide (PI), and 64-channel Parylene-C (PC) shank have been reported using the standard monolithic microfabrication. [21][22][23][24] In the case of electrochemical analysis, a three-electrode system composed of working, reference, and counter electrodes (WE, RE, and CE) is often used. However, to prevent brain damage from the insertion of the third electrode, a two-electrode system is often Monitoring both individual neuronal spikes and neurotransmitters released from a specific brain region plays a significant role in understanding neuronal circuits and brain functionalities. While polymer neural probe offers distinctive advantages of flexibility, optical transparency, and biocompatibility, achieving high-density recording with multifunctionalities and multimodality is still a challenge due to limited microfabrication techniques. Here, a multimodal polymer neural probe array based on a dual-side fabrication process wit...
Optoelectronics devices utilizing organic light‐emitting diodes (OLEDs) are emerging as new platforms for healthcare applications. In particular, wearable optoelectronics such as visual stimulus systems offer a distinctive advantage to intervene in and improve sleep disorders. In this study, two improvements are proposed for transparent OLEDs (TrOLEDs) that will be critical for visual applications. First, zinc sulfide with high surface energy and a high refractive index is explored as a seed and capping layer. An ultra‐thin silver cathode of 8 nm is demonstrated to be feasible in TrOLEDs, and luminous transmittance of 91% is achieved. Second, in general, achieving the operational stability of TrOLEDs with high transmittance is challenging due to the vulnerability of thin electrodes. By introducing a doping process to the electron transport layer, a lifetime comparable to that of control OLEDs with thick cathodes (>90%) is secured. Last, a preclinical model using blue light is proposed to modulate sleep patterns. Melanopsin is stimulated at the highest level of sleep desire, reducing non‐rapid eye movement sleep duration in mice by up to 14%. Based on these results, the proposed TrOLEDs are promising candidates for modulating sleep disorders such as insomnia and narcolepsy–cataplexy with the convenience of wearable form factors.
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