More Like this

1. Neuronal functional connectivity is impaired in a layer dependent manner near chronically implanted intracortical microelectrodes in C57BL6 wildtype mice

   https://doi.org/10.1088/1741-2552/ad5049  

   Chen, Keying; Forrest, Adam M; Burgos, Guillermo Gonzalez; Kozai, Takashi DY (June 2024, Journal of Neural Engineering)

   Abstract Objective.This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near chronically implanted microelectrodes. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how the FBR affects the functional stability of neural circuits near implanted brain–computer interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders.Approach.This study utilized single-shank, 16-channel,100µm site-spacing Michigan-style microelectrodes (3 mm length, 703µm2 site area) that span all cortical layers and the hippocampal CA1 region. Sex balanced C57BL6 wildtype mice (11–13 weeks old) received perpendicularly implanted microelectrode in left primary visual cortex. Electrophysiological recordings were performed during both spontaneous activity and visual sensory stimulation. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of local field potential (LFP) and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation.Main results. The study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations.Significance. This study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study’s understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes. 

   more » « less
2. Penetrating Microindentation of Hyper-soft, Conductive Silicone Neural Interfaces in Vivo Reveals Significantly Lower Mechanical Stresses

   https://doi.org/10.1557/adv.2019.356  

   Sridharan, Arati; Kodibagkar, Vikram; Muthuswamy, Jit (January 2019, MRS Advances)

   ABSTRACT There is growing evidence that minimizing the mechanical mismatch between neural implants and brain tissue mitigates inflammatory, biological responses at the interface under long-term implant conditions. The goal of this study is to develop a brain-like soft, conductive neural interface and use an improvised, penetrating microindentation technique reported by us earlier to quantitatively assess the (a) elastic modulus of the neural interface after implantation, (b) mechanical stresses during penetration of the probe, and (c) periodic stresses at steady-state due to tissue micromotion around the probe. We fabricated poly- dimethylsiloxane (PDMS) matrices with multi-walled carbon nanotubes (MWCNTs) using two distinct but carefully calibrated cross-linking ratios, resulting in hard (elastic modulus∼484 kPa) or soft, brain-like (elastic modulus∼5.7 kPa) matrices, the latter being at least 2 orders of magnitude softer than soft neural interfaces reported so far. Subsequent loading of the hard and soft silicone based matrices with (100% w/w) low-molecular weight PDMS siloxanes resulted in further decrease in the elastic modulus of both matrices. Carbon probes with soft PDMS coating show significantly less maximum axial forces (-587 ± 51.5 µN) imposed on the brain than hard PDMS coated probes (-1,253 ± 252 µN) during and after insertion. Steady-state, physiological micromotion related stresses were also significantly less for soft- PDMS coated probes (55.5 ± 17.4 Pa) compared to hard-PDMS coated probes (141.0 ± 21.7 Pa). The penetrating microindentation technique is valuable to quantitatively assess the mechanical properties of neural interfaces in both acute and chronic conditions. 

   more » « less
3. Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes

   https://doi.org/10.1016/j.biomaterials.2023.122316  

   Chen, Keying; Garcia Padilla, Camila; Kiselyov, Kirill; Kozai, Takashi D.Y. (November 2023, Biomaterials)

   Intracortical microelectrodes that can record and stimulate brain activity have become a valuable technique for basic science research and clinical applications. However, long-term implantation of these microelectrodes can lead to progressive neurodegeneration in the surrounding microenvironment, characterized by elevation in disease-associated markers. Dysregulation of autophagy-lysosomal degradation, a major intracellular waste removal process, is considered a key factor in the onset and progression of neurodegenerative diseases. It is plausible that similar dysfunctions in autophagy-lysosomal degradation contribute to tissue degeneration following implantation-induced focal brain injury, ultimately impacting recording performance. To understand how the focal, persistent brain injury caused by long-term microelectrode implantation impairs autophagylysosomal pathway, we employed two-photon microscopy and immunohistology. This investigation focused on the spatiotemporal characterization of autophagy-lysosomal activity near the chronically implanted microelectrode. We observed an aberrant accumulation of immature autophagy vesicles near the microelectrode over the chronic implantation period. Additionally, we found deficits in autophagy-lysosomal clearance proximal to the chronic implant, which was associated with an accumulation of autophagy cargo and a reduction in lysosomal protease level during the chronic period. Furthermore, our evidence demonstrates reactive astrocytes have myelin-containing lysosomes near the microelectrode, suggesting its role of myelin engulfment during acute implantation period. Together, this study sheds light on the process of brain tissue degeneration caused by longterm microelectrode implantation, with a specific focus on impaired intracellular waste degradation. 

   more » « less
4. Clinical viability of magnetic bead implants in muscle

   https://doi.org/10.3389/fbioe.2022.1010276  

   Taylor, Cameron R.; Clark, William H.; Clarrissimeaux, Ellen G.; Yeon, Seong Ho; Carty, Matthew J.; Lipsitz, Stuart R.; Bronson, Roderick T.; Roberts, Thomas J.; Herr, Hugh M. (October 2022, Frontiers in Bioengineering and Biotechnology)

   Human movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body’s surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post-versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses and exoskeletons and in closed-loop neuroprosthetics to aid recovery from neurological disorders. 

   more » « less
5. High conductivity β-Ga2O3 formed by hot Si ion implantation

   https://doi.org/10.1063/5.0127457  

   Sardar, Arka; Isaacs-Smith, Tamara; Lawson, Jacob; Asel, Thaddeus; Comes, Ryan B.; Merrett, Joseph N.; Dhar, Sarit (December 2022, Applied Physics Letters)

   This work demonstrates the advantage of carrying out silicon ion (Si+) implantation at high temperatures for forming controlled heavily doped regions in gallium oxide. Room temperature (RT, 25 °C) and high temperature (HT, 600 °C) Si implants were carried out into MBE grown (010) β-Ga2O3 films to form ∼350 nm deep Si-doped layers with average concentrations up to ∼1.2 × 1020 cm−3. For such high concentrations, the RT sample was too resistive for measurement, but the HT samples had 82.1% Si dopant activation efficiency with a high sheet electron concentration of 3.3 × 1015 cm−2 and an excellent mobility of 92.8 cm2/V·s at room temperature. X-ray diffraction measurements indicate that HT implantation prevents the formation of other Ga2O3 phases and results in reduced structural defects and lattice damage. These results are highly encouraging for achieving ultra-low resistance heavily doped Ga2O3 layers using ion implantation. 

   more » « less