Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.

BACKGROUND: Few treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory. OBJECTIVE: Here, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration. METHODS: 59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5-12 Hz), low gamma (30-50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)). RESULTS: Injection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner. CONCLUSIONS: These findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.

Stretchable Nanolayered Thermoelectric Energy Harvester on Complex and Dynamic Surfaces.

Thermoelectric generators (TEGs) provide a unique solution for energy harvesting from waste heat, presenting a potential solution for green energy. However, traditional rigid and flexible TEGs cannot work on complex and dynamic surfaces. Here, we report a stretchable TEG (S-TEG) (over 50% stretchability of the entire device) that is geometrically suitable for various complex and dynamic surfaces of heat sources. The S-TEG consists of hot-pressed nanolayered p-(Sb2Te3) and n-(Bi2Te3)-type thermoelectric couple arrays and exploits the wavy serpentine interconnects to integrate all units. The internal resistance of a 10 × 10 array is 22 ohm, and the output power is ∼0.15 mW/cm2 at ΔT = 19 K on both developable and nondevelopable surfaces, which are much improved compared with those of existing S-TEGs. The energy harvesting of S-TEG from the dynamic surfaces of the human skin offers a potential energy solution for the wearable devices for health monitoring.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

Measuring spatial visual loss in rats by retinotopic mapping of the superior colliculus using a novel multi-electrode array technique.

BACKGROUND: The retinotopic map property of the superior colliculus (SC) is a reliable indicator of visual functional changes in rodents. Electrophysiological mapping of the SC using a single electrode has been employed for measuring visual function in rat and mouse disease models. Single electrode mapping is highly laborious requiring long-term exposure to the SC surface and prolonged anesthetic conditions that can adversely affect the mapping data. NEW METHOD: To avoid the above-mentioned issues, we fabricated a fifty-six (56) electrode multi-electrode array (MEA) for rapid and reliable visual functional mapping of the SC. Since SC is a dome-shaped structure, the array was made of electrodes with dissimilar tip lengths to enable simultaneous and uniform penetration of the SC. RESULTS: SC mapping using the new MEA was conducted in retinal degenerate (RD) Royal College of Surgeons (RCS) rats and rats with focal retinal damage induced by green diode laser. For SC mapping, the MEA was advanced into the SC surface and the visual activities were recorded during full-filed light stimulation of the eye. Based on the morphological examination, the MEA electrodes covered most of the exposed SC area and penetrated the SC surface at a relatively uniform depth. MEA mapping in RCS rats (n=9) demonstrated progressive development of a scotoma in the SC that corresponded to the degree of photoreceptor loss. MEA mapping in the laser damaged rats demonstrated the presence of a scotoma in the SC area that corresponded to the location of retinal laser injury. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: The use of MEA for SC mapping is advantageous over single electrode recording by enabling faster recordings and reducing anesthesia time. This study establishes the feasibility of the MEA technique for rapid and efficient SC mapping, particularly advantageous for evaluating therapeutic effects in retinal degenerate rat disease models.

Flexible, biodegradable ultrasonic wireless electrotherapy device based on highly self-aligned piezoelectric biofilms.

Biodegradable piezoelectric devices hold great promise in on-demand transient bioelectronics. Existing piezoelectric biomaterials, however, remain obstacles to the development of such devices due to difficulties in large-scale crystal orientation alignment and weak piezoelectricity. Here, we present a strategy for the synthesis of optimally orientated, self-aligned piezoelectric γ-glycine/polyvinyl alcohol (γ-glycine/PVA) films via an ultrasound-assisted process, guided by density functional theory. The first-principles calculations reveal that the negative piezoelectric effect of γ-glycine originates from the stretching and compression of glycine molecules induced by hydrogen bonding interactions. The synthetic γ-glycine/PVA films exhibit a piezoelectricity of 10.4 picocoulombs per newton and an ultrahigh piezoelectric voltage coefficient of 324 × 10-3 volt meters per newton. The biofilms are further developed into flexible, bioresorbable, wireless piezo-ultrasound electrotherapy devices, which are demonstrated to shorten wound healing by ~40% and self-degrade in preclinical wound models. These encouraging results offer reliable approaches for engineering piezoelectric biofilms and developing transient bioelectronics.

Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Ultrasound Concave 2-D Ring Array for Retinal Stimulation.

An ultrasound concave 2-D ring array transducer was designed for applications in visual stimulation of the retina with a long-term goal to restore vision in individuals with intact neurons but suffering blindness due to retinopathies. The array was synthesized and has a frequency of 20 MHz (0.075-mm wavelengths in water), 18-mm focal length (the curvature of the concave array), 1004 elements (with a pitch of 4.0 wavelengths), and inner and outer diameters of 9 and 14 mm, respectively. Wave patterns produced with the array at the focal distance were simulated. Results show that the wave patterns obtained can achieve a full-width-at-half-maximum (FWHM) resolution of 0.147 mm that is very close to the FWHM diffraction limit (0.136 mm). In addition, a scaled experiment at a lower frequency of 2.5 MHz was performed. The result is very close to those obtained with the simulations.

Estimating Thrombus Elasticity by Shear Wave Elastography to Evaluate Ultrasound Thrombolysis for Thrombus With Different Stiffness.

OBJECTIVE: There is uncertainty about deep vein thrombosis standard treatment as thrombus stiffness alters each case. Here, we investigated thrombus' stiffness of different compositions and ages using shear wave elastography (SWE). We then studied the effectiveness of ultrasound-thrombolysis on different thrombus compositions. METHODS: Shear waves generated through mechanical shaker and traveled along thrombus of different hematocrit (HCT) levels, whereas 18-MHz ultrasound array used to detect wave propagation. Thrombus' stiffness was identified by the shear wave speed (SWS). In thrombolysis, a 3.2 MHz focused transducer was applied to different thrombus compositions using different powers. The thrombolysis rate was defined as the percentage of weight loss. RESULTS: The estimated average SWS of 20%, 40%, and 60% HCT thrombus were 0.75 m/s, 0.44 m/s, and 0.32 m/s, respectively. For Thrombolysis, the percentage weight loss at 8 MPa Negative pressure for the same HCT groups were 23.1%, 35.29%, and 39.66% respectively. CONCLUSION: SWS is inversely related to HCT level and positively related to thrombus age. High HCT thrombus had higher weight loss compared to low HCT. However, the difference between 20% and 40% HCT was more significant than between 40% and 60% HCT in both studies. Our results suggest that thrombus with higher SWS require more power to achieve the same thrombolysis rate as thrombus with lower SWS. SIGNIFICANCE: Characterizing thrombus elastic property undergoing thrombolysis enables evaluation of ultrasound efficacy for fractionating thrombus and reveals the appropriate ultrasound parameters selection to achieve a certain thrombolysis rate in the case of a specific thrombus stiffness.

Growing recyclable and healable piezoelectric composites in 3D printed bioinspired structure for protective wearable sensor.

Bionic multifunctional structural materials that are lightweight, strong, and perceptible have shown great promise in sports, medicine, and aerospace applications. However, smart monitoring devices with integrated mechanical protection and piezoelectric induction are limited. Herein, we report a strategy to grow the recyclable and healable piezoelectric Rochelle salt crystals in 3D-printed cuttlebone-inspired structures to form a new composite for reinforcement smart monitoring devices. In addition to its remarkable mechanical and piezoelectric performance, the growth mechanisms, the recyclability, the sensitivity, and repairability of the 3D-printed Rochelle salt cuttlebone composite were studied. Furthermore, the versatility of composite has been explored and applied as smart sensor armor for football players and fall alarm knee pads, focusing on incorporated mechanical reinforcement and electrical self-sensing capabilities with data collection of the magnitude and distribution of impact forces, which offers new ideas for the design of next-generation smart monitoring electronics in sports, military, aerospace, and biomedical engineering.

Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo.

The optic nerve is the second cranial nerve (CN II) that connects and transmits visual information between the retina and the brain. Severe damage to the optic nerve often leads to distorted vision, vision loss, and even blindness. Such damage can be caused by various types of degenerative diseases, such as glaucoma and traumatic optic neuropathy, and result in an impaired visual pathway. To date, researchers have not found a viable therapeutic method to restore the impaired visual pathway; however, in this paper, a newly synthesized model is proposed to bypass the damaged portion of the visual pathway and set up a direct connection between a stimulated visual input and the visual cortex (VC) using Low-frequency Ring-transducer Ultrasound Stimulation (LRUS). In this study, by utilizing and integrating various advanced ultrasonic and neurological technologies, the following advantages are achieved by the proposed LRUS model: 1. This is a non-invasive procedure that uses enhanced sound field intensity to overcome the loss of ultrasound signal due to the blockage of the skull. 2. The simulated visual signal generated by LRUS in the visual-cortex-elicited neuronal response in the visual cortex is comparable to light stimulation of the retina. The result was confirmed by a combination of real-time electrophysiology and fiber photometry. 3. VC showed a faster response rate under LRUS than light stimulation through the retina. These results suggest a potential non-invasive therapeutic method for restoring vision in optic-nerve-impaired patients using ultrasound stimulation (US).