An official website of the United States government
Abstract Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, usingThy1-ChR2-YFPmice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.
more »
« less
High‐Density, Conformable Conducting Polymer‐Based Implantable Neural Probes for the Developing Brain
Abstract Neurologic and neuropsychiatric disorders substantially impact the pediatric population, but there is a lack of dedicated devices for monitoring the developing brain in animal models, leading to gaps in mechanistic understanding of how brain functions emerge and their disruption in disease states. Due to the small size, fragility, and high water content of immature neural tissue, as well as the absence of a hardened skull to mechanically support rigid devices, conventional neural interface devices are poorly suited to acquire brain signals without inducing damage. Here, the authors design conformable, implantable, conducting polymer‐based probes (NeuroShanks) for precise targeting in the developing mouse brain without the need for skull‐attached, rigid mechanical support structures. These probes enable the acquisition of high spatiotemporal resolution neurophysiologic activity from superficial and deep brain regions across unanesthetized behavioral states without causing tissue disruption or device failure. Once implanted, probes are mechanically stable and permit precise, stable signal monitoring at the level of the local field potential and individual action potentials. These results support the translational potential of such devices for clinically indicated neurophysiologic recording in pediatric patients. Additionally, the role of organic bioelectronics as an enabling technology to address questions in developmental neuroscience is revealed.
more »
« less
- Award ID(s):
- 2219891
- PAR ID:
- 10506137
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 13
- Issue:
- 24
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract To understand the underlying mechanisms of progressive neurophysiological phenomena, neural interfaces should interact bi-directionally with brain circuits over extended periods of time. However, such interfaces remain limited by the foreign body response that stems from the chemo-mechanical mismatch between the probes and the neural tissues. To address this challenge, we developed a multifunctional sensing and actuation platform consisting of multimaterial fibers intimately integrated within a soft hydrogel matrix mimicking the brain tissue. These hybrid devices possess adaptive bending stiffness determined by the hydration states of the hydrogel matrix. This enables their direct insertion into the deep brain regions, while minimizing tissue damage associated with the brain micromotion after implantation. The hydrogel hybrid devices permit electrophysiological, optogenetic, and behavioral studies of neural circuits with minimal foreign body responses and tracking of stable isolated single neuron potentials in freely moving mice over 6 months following implantation.more » « less
-
Neural implants that are based on mechanically adaptive polymers (MAPs) and soften upon insertion into the body have previously been demonstrated to elicit a reduced chronic tissue response than more rigid devices fabricated from silicon or metals, but their processability has been limited. Here we report a negative photoresist approach towards physiologically responsive MAPs. We exploited this framework to create cross-linked terpolymers of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate and 2-ethylhexyl methacrylate by photolithographic processes. Our systematic investigation of this platform afforded an optimized composition that exhibits a storage modulus E ′ of 1.8 GPa in the dry state. Upon exposure to simulated physiological conditions the material swells slightly (21% w/w) leading to a reduction of E ′ to 2 MPa. The large modulus change is mainly caused by plasticization, which shifts the glass transition from above to below 37 °C. Single shank probes fabricated by photolithography could readily be implanted into a brain-mimicking gel without buckling and viability studies with microglial cells show that the materials display excellent biocompatibility.more » « less
-
Neural implants that are based on mechanically adaptive polymers (MAPs) and soften upon insertion into the body have previously been demonstrated to elicit a reduced chronic tissue response than more rigid devices fabricated from silicon or metals, but their processability has been limited. Here we report a negative photoresist approach towards physiologically responsive MAPs. We exploited this framework to create cross-linked terpolymers of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate and 2-ethylhexyl methacrylate by photolithographic processes. Our systematic investigation of this platform afforded an optimized composition that exhibits a storage modulus E′ of 1.8 GPa in the dry state. Upon exposure to simulated physiological conditions the material swells slightly (21% w/w) leading to a reduction of E′ to 2 MPa. The large modulus change is mainly caused by plasticization, which shifts the glass transition from above to below 37 °C. Single shank probes fabricated by photolithography could readily be implanted into a brain-mimicking gel without buckling and viability studies with microglial cells show that the materials display excellent biocompatibility.more » « less
-
Abstract Understanding near infrared light propagation in tissue is vital for designing next generation optical brain imaging devices. Monte Carlo (MC) simulations provide a controlled mechanism to characterize and evaluate contributions of diverse near infrared spectroscopy (NIRS) sensor configurations and parameters. In this study, we developed a multilayer adult digital head model under both healthy and clinical settings and assessed light‐tissue interaction through MC simulations in terms of partial differential pathlength, mean total optical pathlength, diffuse reflectance, detector light intensity and spatial sensitivity profile of optical measurements. The model incorporated four layers: scalp, skull, cerebrospinal‐fluid and cerebral cortex with and without a customizable lesion for modeling hematoma of different sizes and depths. The effect of source‐detector separation (SDS) on optical measurements' sensitivity to brain tissue was investigated. Results from 1330 separate simulations [(4 lesion volumes × 4 lesion depths for clinical +3 healthy settings) × 7 SDS × 10 simulation = 1330)] each with 100 million photons indicated that selection of SDS is critical to acquire optimal measurements from the brain and recommended SDS to be 25 to 35 mm depending on the wavelengths to obtain optical monitoring of the adult brain function. The findings here can guide the design of future NIRS probes for functional neuroimaging and clinical diagnostic systems.more » « less
