Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Second-Generation Polyamidoamine Dendrimer Conjugated with Oligopeptides Can Enhance Plasmid DNA Delivery In Vitro.

Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface. In this study, we successfully conjugated an RRHRH oligopeptide to the surface of PAMAM generation 2 (PAMAM G2) to create RRHRH-PAMAM G2. This construction aims to condense plasmid DNA (pDNA) and facilitate its penetration into cell membranes, leading to its promising potential for gene therapy. RRHRH-PAMAM G2/pDNA complexes were smaller than 100 nm and positively charged. Nano-polyplexes can enter the cell and show a high transfection efficiency after 24 h of transfection. The RRHRH-PAMAM G2 was non-toxic to HeLa, NIH3T3, A549, and MDA-MB-231 cell lines. These results strongly suggest that RRHRH-PAMAM G2 holds promise as a gene carrier for gene therapy owing to its biocompatibility and ability to deliver genes to the cell.

Copper-based etalon filter using antioxidant graphene layer.

Copper is a low-cost material compared to silver and gold, having high reflectivity in the near infrared spectral range as well as good electrical and thermal conductivity. Its properties make it a good candidate for metal-based low-cost multilayer thin-film devices and optical components. However, its high reflectance in the devices is reduced because copper is easily oxidized. Here, we suggest a copper-based Fabry-Perot optical filter consisting of a thin dielectric layer stacked between two copper films, which can realize low-cost production compared to a conventional silver-based etalon filter. The reduced performance due to the inherent oxidation of the copper surface can be overcome by passivating the copper films with monolayer graphene. The anti-oxidation of copper film is investigated by optical microscopy, x-ray photoelectron spectroscopy, and transmission measurement in UV-vi spectral ranges. Our results show that the graphene coating can be expanded for various metal-based optical devices in terms of anti-corrosion.

Understanding of Defect Passivation Effect on Wide Band Gap p-i-n Perovskite Solar Cell.

The wide band gap perovskite solar cells (PSCs) have attracted considerable attention for their great potential as top cells in high efficiency tandem cell application. However, the photovoltaic performance and stability of PSCs are constrained by nonradiative recombination, primarily stemming from defects within the bulk and at the interface of charge transport layer/perovskite and phase segregation. In this study, we systematically investigated the effects of 2-thiopheneethylammonium chloride (TEACl) on a wide band gap (∼1.67 eV) Cs0.15FA0.65MA0.20Pb(I0.8Br0.2)3 (CsFAMA) perovskite solar cell. TEACl was employed as a passivation layer between the perovskite and electron transport layer (ETL). With TEACl treatment, charged defects responsible for sub-band absorption and electrostatic potential fluctuation were effectively suppressed by the passivation of bulk defects. The incorporation of TEACl, which led to the formation of a TEA2PbX4/Perovskite (2D/3D) heterojunction, facilitated better band alignment and effective passivation of interface defects at the ETL/CsFAMA. Owing to these beneficial effects, the TEACl passivated PSC achieved a photo conversion efficiency (PCE) of 19.70% and retained ∼85% of initial PCE over ∼1900 h, surpassing the performance of the untreated PSC, which exhibited a PCE of 16.69% and retained only ∼37% of its initial PCE.

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS and fUS revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We saw a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with the brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV response with peak CBV, activated area, and correlation coefficient increasing with ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalizes and linearly correlates with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths and the evoked hemodynamic responses colocalized and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as an understanding of how FUS displaces brain tissue and affects cerebral hemodynamics.

Modulating Lipid Nanoparticles with Histidinamide-Conjugated Cholesterol for Improved Intracellular Delivery of mRNA.

Recently, mRNA-based therapeutics, including vaccines, have gained significant attention in the field of gene therapy for treating various diseases. Among the various mRNA delivery vehicles, lipid nanoparticles (LNPs) have emerged as promising vehicles for packaging and delivering mRNA with low immunogenicity. However, while mRNA delivery has several advantages, the delivery efficiency and stability of LNPs remain challenging for mRNA therapy. In this study, an ionizable helper cholesterol analog, 3ß[L-histidinamide-carbamoyl] cholesterol (Hchol) lipid is developed and incorporated into LNPs instead of cholesterol to enhance the LNP potency. The pKa values of the Hchol-LNPs are ≈6.03 and 6.61 in MC3- and SM102-based lipid formulations. Notably, the Hchol-LNPs significantly improve the delivery efficiency by enhancing the endosomal escape of mRNA. Additionally, the Hchol-LNPs are more effective in a red blood cell hemolysis at pH 5.5, indicating a synergistic effect of the protonated imidazole groups of Hchol and cholesterol on endosomal membrane destabilization. Furthermore, mRNA delivery is substantially enhanced in mice treated with Hchol-LNPs. Importantly, LNP-encapsulated SARS-CoV-2 spike mRNA vaccinations induce potent antigen-specific antibodies against SARS-CoV-2. Overall, incorporating Hchol into LNP formulations enables efficient endosomal escape and stability, leading to an mRNA delivery vehicle with a higher delivery efficiency.

Efficiency Improvement of Narrow Band Gap Cu(In,Ga)(S,Se)2 Solar Cell with Alkali Treatment via Aqueous Spray Pyrolysis Deposition.

The chalcopyrite Cu(In,Ga)(S,Se)2 (CIGSSe) solar cell with a low band gap is a promising candidate for use as the bottom cell in high-efficiency tandem solar cells. In this study, we investigated narrow band gap CIGSSe solar cells, both with and without alkali treatment. The CIGSSe absorbers were fabricated using aqueous spray pyrolysis in an air environment, with the precursor solution prepared by dissolving constituent metal salts. We found that the power conversion efficiency (PCE) of the fabricated solar cell was significantly enhanced when rubidium postdeposition treatment (PDT) was applied to the CIGSSe absorber. The Rb-PDT facilitates defect passivation and a downshift of the valence band maximum of the CIGSSe absorber, thereby improving the power conversion efficiency and all device parameters. Due to these beneficial effects, a PCE of ∼15% was obtained with an energy band gap of less than 1.1 eV, making it suitable for use as the bottom cell in a highly efficient tandem solar cell.

Synaptic Segmented Transistor with Improved Linearity by Schottky Junctions and Accelerated Speed by Double-Layered Nitride.

Neuromorphic devices have been extensively studied to overcome the limitations of a von Neumann system for artificial intelligence. A synaptic device is one of the most important components in the hardware integration for a neuromorphic system because a number of synaptic devices can be connected to a neuron with compactness as high as possible. Therefore, synaptic devices using silicon-based memory, which are advantageous for a high packing density and mass production due to matured fabrication technologies, have attracted considerable attention. In this study, a segmented transistor devoted to an artificial synapse is proposed for the first time to improve the linearity of the potentiation and depression (P/D). It is a complementary metal oxide semiconductor (CMOS)-compatible device that harnesses both non-ohmic Schottky junctions of the source and drain for improved weight linearity and double-layered nitride for enhanced speed. It shows three distinct and unique segments in drain current-gate voltage transfer characteristics induced by Schottky junctions. In addition, the different stoichiometries of SixNy for a double-layered nitride is utilized as a charge trap layer for boosting the operation speed. This work can bring the industry potentially one step closer to realizing the mass production of hardware-based synaptic devices in the future.

General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents.

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head-fixed, anesthesia-dependent, and acute, limiting clinical translatability. Here, this work reports a general-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact-free stimulation and simultaneous neural recording. Using the general-purpose system, it can be observed that state-dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

Effect of Metal-Precursor Stacking Order on Volume-Defect Formation in CZTSSe Thin Film: Formation Mechanism of Blisters and Nanopores.

In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.

Reassessing the high proportion of involuntary psychiatric hospital admissions in South Korea.

The 2007 WHO-AIMS report on the mental health system of South Korea documented progress towards a national mental health plan, protection of human rights, and growth of community based services. Yet concern was expressed that the high proportion of involuntary to total psychiatric hospitalizations (92%) may indicate an excessively coercive system. Involuntary hospitalization in Korea rose from 117 to 132 (per 100,000) between 2000 and 2006. In 2000, the median rate in the European Union (EU) was 74 per 100,000 (Range: 6-218). While Korea's involuntary hospitalization rate is within the EU range, its proportion of involuntary hospitalizations is three times that of the highest EU country (30%, Sweden). Underdevelopment of voluntary psychiatric services and culturally mandated family referrals resulting in involuntary hospitalization are apparent reasons for the high proportion of involuntary hospitalizations. Population-based rates per 100,000 more accurately describe involuntary hospitalization than the proportion (ratio) measure used in the WHO-AIMS reports.

Transcranial focused ultrasound stimulation with high spatial resolution.

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 = 38). RESULTS: The full-width at half maximum (FWHM) focal volume of our dual-crossed transducer system was under 0.52 µm3. 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 dual-crossed 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.

Vital signal sensing and manipulation of a microscale organ with a multifunctional soft gripper.

Soft grippers that incorporate functional materials are important in the development of mechanically compliant and multifunctional interfaces for both sensing and stimulating soft objects and organisms. In particular, the capability for firm and delicate grasping of soft cells and organs without mechanical damage is essential to identify the condition of and monitor meaningful biosignals from objects. Here, we report a millimeter-scale soft gripper based on a shape memory polymer that enables manipulating a heavy object (payload-to-weight ratio up to 6400) and grasping organisms at the micro/milliscale. The silver nanowires and crack-based strain sensor embedded in this soft gripper enable simultaneous measurement of the temperature and pressure on grasped objects and offer temperature and mechanical stimuli for the grasped object. We validate our miniaturized soft gripper by demonstrating that it can grasp a snail egg while simultaneously applying a moderate temperature stimulation to induce hatching process and monitor the heart rate of a newborn snail. The results present the potential for widespread utility of soft grippers in the area of biomedical engineering, especially in the development of conditional or closed-loop interfacing with microscale biotissues and organisms.

A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients.

RATIONALE: Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. OBJECTIVES: This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. MATERIALS AND METHODS: Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. RESULTS: Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. CONCLUSIONS: These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.

Device Characteristics of Band gap Tailored 10.04% Efficient CZTSSe Solar Cells Sprayed from Water-Based Solution.

A diverse S/(S + Se) ratio of Cu2ZnSn(Sx,Se1-x)4 (CZTSSe) thin-film solar cells is derived by the water-based spray pyrolysis approach. By fine-tuning the S/(S + Se) ratio, base CZTSSe device efficiency has significantly improved from 7.02 to 10.04% by minimizing the Voc deficit up to 616 mV and increasing fill factor (FF) from 56.42 to 62.38%. As the S/(S + Se) ratio was increased from 0 to 0.4, surface compactness was observed to be improved with slightly decreased grain size, which increased shunt resistance and resultantly increased FF. However, when S-alloying was more than S/(S + Se) = 0.4, grain size decreased too much and had a detrimental effect on device performance. To deeply understand the role effect of the S/(S + Se) ratio, detailed spectroscopic analysis is performed with admittance spectroscopy, temperature-dependent current-voltage characteristic (J-V-T), time-resolved photoluminescence, and Raman depth profiling. Experimental results revealed that the different power conversion efficiency limiting factors were developed with various S/(S + Se) ratios. High density of deep defect states generated with the S/(S + Se) ≥ 40% content and larger conduction band offset observed with red kink were formed in the Se/(S + Se) ≥ 80% content. Hence, in order to get the high-efficient CZTSSe solar cell, fine tuning of the S/(S + Se) ratio is necessary.

Sulfur-Alloying Effects on Cu(In,Ga)(S,Se)2 Solar Cell Fabricated Using Aqueous Spray Pyrolysis.

We fabricated Cu(In,Ga)(S,Se)2 (CIGSSe) solar cells using aqueous spray based deposition, which is inexpensive and covers a large area. To apply the sprayed film to a photoabsorber of a solar cell, post-sulfo-selenization was carried out. Through the sulfo-selenization process, we were able to fabricate various S-alloyed CIGSSe films from S/(S + Se) = 0 (S-0.0) to S/(S + Se) = 0.4 (S-0.4). CIGSSe solar cells were made with the S-alloyed CIGSSe absorbers. Power conversion efficiency of CIGSSe solar cell was found to be increased with S-alloying up to S-0.3, and the best efficiency of 10.89% was obtained with the S-0.3 CIGSSe absorber. Comparison study of S-alloyed CIGSSe solar cells showed that enhanced efficiency in S-0.3 solar cell is due to the increased open-circuit voltage and an improved fill factor, which is induced by S-alloying. In addition, admittance spectroscopy revealed that the defect density of the deep level was developed in the S-alloyed S-0.3 CIGSSe absorber. However, the defect density was observed to be rather reduced. Details of characterization and analysis results are discussed in this paper.

Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals.

BACKGROUND: Current transcranial ultrasound stimulation for small animal in vivo experiment is limited to acute stimulation under anesthesia in stereotaxic fixation due to bulky and heavy curved transducers. METHODS: We developed a miniaturized ultrasound ring array transducer which is capable of invoking motor responses through neuromodulation of freely-moving awake mice. RESULTS: The developed transducer is a 32-element, 183-kHz ring array with a weight of 0.035 g (with PCB: 0.73 g), a diameter of 8.1 mm, a focal length of 2.3 mm, and lateral resolution of 2.75 mm. By developing an affixation scheme suitable for freely-moving animals, the transducer was successfully coupled to the mouse brain and induced motor responses in both affixed and awake states. CONCLUSION: Ultrasound neuromodulation of a freely-moving animal is now possible using the developed lightweight and compact system to conduct a versatile set of in vivo experiments.

Nanoscale FET-Based Transduction toward Sensitive Extended-Gate Biosensors.

Owing to their simple and low-cost architecture, extended-gate biosensors based on the combination of a disposable sensing part and a reusable transducer have been widely utilized for the label-free electrical detection of chemical and biological species. Previous studies have demonstrated that sensitive and selective detection of ions and biomolecules can be achieved by controlled modification of the sensing part with an ion-selective membrane and receptors of interest. However, no systematic studies have been performed on the impact of the transducer on sensing performance. In this paper, we introduce the concept of a nanoscale field-effect transistor (FET) as a reusable and sensitive transducer for extended-gate biosensors. The capacitive effect from the external sensing part can degrade the sensing performance, but the nanoscale FET can reduce this effect. The nanoscale FET with a gate-all-around (GAA) structure exhibits a higher pH sensitivity than a commercially available FET, which is widely used in conventional extended-gate biosensors. A sensitivity reduction is observed for the commercial FET, whereas the pH sensitivity is insensitive to the area of the sensing region in the nanoscale FET, thus allowing the scaling of the detection area. Our analysis based on a capacitive model suggests that the high pH sensitivity in the compact sensing area originates from the small input capacitance of the nanoscale FET transducer. Moreover, a decrease in the nanowire width of the GAA FET leads to an improvement in the pH sensitivity. The extended-gate approach with the nanoscale FET-based transduction can pave the way for a highly sensitive analysis of chemical and biological species with a small sample volume.

Capacitive Micromachined Ultrasonic Transducer (CMUT) ring array for transcranial ultrasound neuromodulation.

Non-invasive brain stimulation of small animals plays an important role in neuroscience especially in understanding fundamental mechanisms of brain disorders. Here, we report a miniaturized ultrasound transducer array designed for non-invasive brain stimulation of mouse for the first time. We designed and fabricated a Capacitive Micromachined Ultrasonic Transducer (CMUT) ring array that operates at 183 kHz in immersion. The fabricated transducer ring array exhibited a focal length of 2.25 mm and a maximum intensity of 175 mW/cm2. Because the array was fabricated in a ring shape, a natural focus was achieved and thus, no additional focusing circuitries or acoustic lens were required. Thus, a compact packaging was achieved with minimum surgical procedures for in vivo mouse experiments. Using the developed micromachined transducer array and simple packaging, we successfully induced the motor responses of a mouse. The success rate of ultrasound stimulation was quantified by recording the electromyography (EMG) signal during the stimulation. While the current ultrasound neuromodulation system is limited to acute experiments, the presented light (< 1 g) and compact ultrasound neuromodulation system with a natural focus would enable chronic ultrasound neuromodulation experiments on freely-moving mice.

Improved Target Specificity of Transcranial Focused Ultrasound Stimulation (TFUS) using Double-Crossed Ultrasound Transducers.

Ultrasound neuromodulation is a promising stimulation modality because of its non-invasiveness, focusing and steering capability, and relatively high spatial resolution compared to the other stimulation modalities. However, despite the high lateral resolution, the ultrasound beam in the axial direction is relatively long, especially when compared to the small size of the mouse brain. Here, we report a new ultrasound focusing technique for small animal in vivo experiments where a high spatial resolution in both lateral and axial directions is achieved by crossing two ultrasound beams. The focal volume of a full width half maximum (FWHM) of our proposed system is only 0.161 mm3 and the focal diameter in the axial direction is about 1 mm, which is ten times smaller than the previously reported ultrasound neuromodulation system. Thus, the proposed system enables targeting a sub-region of a mouse brain using ultrasound for the first time. We also demonstrate successful stimulation of the motor cortex through in vivo mice experiments where the movement of forepaw of the mouse was observed using the double-crossed ultrasound transducers. Moreover, by sweeping the focal point in the z-axis and measuring the success rate of stimulated movements, we show that our double-transducer system targeted a region with 2 mmresolution in the dorsal-ventral (DV) coordinates. The success rate of the double-crossed ultrasound stimulation was quantified by recording the electromyography (EMG) signals during the stimulation. Our results show that the double-crossed ultrasound transducer system with a ten times higher spatial resolution enables highly specific and noninvasive stimulation of small animals and thus enables versatile in vivo experiments to study functional connectivities of brain circuits.