Browsing by Author "Xie, Chong"

Now showing 1 - 9 of 9
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    An In Vivo Platform for Rebuilding Functional Neocortical Tissue
    (MDPI, 2023) Quezada, Alexandra; Ward, Claire; Bader, Edward R.; Zolotavin, Pavlo; Altun, Esra; Hong, Sarah; Killian, Nathaniel J.; Xie, Chong; Batista-Brito, Renata; Hébert, Jean M.
    Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by one week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of a concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.
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    Chronic large-scale recording and stimulation enabled by ultra-flexible high-density neural probes and an implantation robot
    (2023-10-17) Wang, Weinan; Xie, Chong
    Ultraflexible nanoelectronic neural probes have shown their capabilities in stable long-term recording at a wide range of spatial-temporal scales and a high resolution from animal brains, thanks to their miniaturized electrode configurations and close-to-tissue mechanical compliance that contribute to a glial scar-free interface. These features also enable them to be integrated with imaging systems for neuron ensemble and vasculature study. However, current neural recording devices cannot record and process data from a large across-brain-region scale at a cellular level, while ensuring the free movement of an animal. Here, we present electron-beam lithography (EBL) fabricated high-density flexible probes with up to 1024 channels. They record spikes from free-moving rats with little amplitude degradation over up to 3 months. The ultraflexible polymer probes can be integrated with a lightweight, densely packed application-specific integrated circuit (ASIC) that enables simultaneous multi-thousand channel recording. We further propose a semi-automated implantation robot that has 32 individually and simultaneously addressable arms that integrate with probes, capable of inserting the shanks into a rodent’s brain at any geometric configuration at a wide range of speed per user’s need. The robot provides a reliable solution for parallel and independent insertion, which is useful for reducing implantation time and the adverse biological response. To our knowledge, it is so far the largest configurable parallel implantation system. We believe the high-density probes in combination with the high degree-of-freedom manipulation of the implantation will be an enabling technology in neuroscience studies in animal models, as well as in clinical applications.
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    Chronic large-scale recording with ultraflexible electrode arrays for studying neural codes and their stability
    (2024-11-07) Zhu, Hanlin; Xie, Chong
    A central question in neuroscience is identifying neural codes that stably represent external variables across time. Using mice visual perception as the experimental paradigm, I focused on the debate between rate code versus temporal code based neural representation and depicted their differential contribution to the duality of neural representation stability and drift. Despite the pivotal distinction between spike counting based rate code and spike timing aware temporal codes, previous studies have yet to unveil the role of temporal code in long-term visual representation due to technical constraints. Past reports on drift in visual code over time predominantly relied on calcium imaging, which lacked the temporal resolution to capture fast-spiking dynamics and were further confounded by interferences such as photobleaching, leaving a gap in our comprehension of these complexities in neural code. While such investigation could have been carried out with electrophysiological recordings that resolves fast spiking dynamics, the scale and longevity necessary to study representation stability has not been achieved with conventional rigid electrodes. Our group overcomes these hurdles with large scale implantation of ultraflexible nanoelectronic threads (NETs) electrodes, which provide unprecedented longitudinal recordings across many neurons, while minimizing tissue-electrode interface instability. In this thesis, I a) established a platform to map visual response properties of neural units from > 1000 channels of ultraflexible electrodes. b) developed a method to track same units recorded by these ultraflexible electrode arrays. c) compared the stability of different neural codes by longitudinally tracking > 1000 single neuron units from 5 mice over 15 consecutive days from animals subjected to repeated, diverse visual stimuli every day. Our result reveals that considering the fast temporal dynamics of neuronal spikes (temporal code) enhances the stability of individual neuron tuning, neuronal population representation, and decoding accuracy compared to rate code. Thus, temporal coding, a mechanism that operates on the millisecond scale of neural communication, might be a fundamental principle that supports the consistency of sensory experiences, amidst the ever-changing brain states and synaptic strengths.
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    EMvelop Stimulation: Minimally Invasive Deep Brain Stimulation using Temporally Interfering Electromagnetic Waves
    (2024-04-18) Ahsan, Fatima; Aazhang, Behnaam; Robinson, Jacob T; Xie, Chong; Szablowski, Jerzy O
    This thesis focuses on developing a novel brain stimulation methodology by using temporally interfering gigahertz (GHz) electromagnetic (EM) waves, termed EMvelop stimulation. Our work on EMvelop stimulation addresses two key aspects of developing this novel methodology: obtaining high electric field intensity and focality at target regions deep inside the brain tissue and fast and robust data-driven electric field estimation. First, we validate the idea of EMvelop stimulation using multi-physics modeling and algorithmic optimization simulations. We show that at GHz frequencies, we can create antenna arrays at the scale of a few centimeters or less that can be endocranially implanted to enable longitudinal stimulation and circumvent signal attenuation due to the scalp and skull. Furthermore, owing to the small wavelength of GHz EM waves, we can optimize both amplitudes and phases of the EM waves to achieve high intensity and focal stimulation at targeted regions. We develop a simulation framework investigating the propagation of GHz EM waves and the corresponding heat generated in the brain tissue. We propose two optimization flows to identify antenna current amplitudes and phases for either maximal intensity or maximal focality transmission of the interfering electric fields with EM waves safety constraint. A representative result of our study is that with two endocranially implanted arrays of size 4.2 cm x 4.7 cm each, we can achieve an intensity of 12 V/m with a focality of 3.6 cm at a target deep in the brain tissue. To the best of our knowledge, this is the first time the idea of EMvelop stimulation was proposed and investigated, and we demonstrated its benefits over prior methodologies of electrical stimulation. Second, a common factor across electromagnetic methodologies of brain stimulation is the optimization of essential dosimetry parameters, like amplitude, phase, and the location of one or more transducers, which controls the stimulation strength and targeting precision. Since obtaining in-vivo measurements for the electric field distribution inside the biological tissue is challenging, physics-based simulators are used. However, these physics-based simulators are computationally expensive and time-consuming, making computing the electric field repeatedly for optimization purposes computationally prohibitive. To overcome this issue, we trained a U-Net model using 14 segmented human magnetic resonance images (MRIs). Once trained, the model inputs a segmented human MRI and the antenna location and outputs the corresponding electric field. At 1.5 GHz, on the validation dataset consisting of 6 patients, we can estimate the electric field with the magnitude of complex correlation coefficient of 0.978. Additionally, we could calculate the electric field with a mean time of 4.4 ms for a potential antenna location. On average, this is at least 1200 times faster than the time required by state-of-the-art physics-based simulator COMSOL. The significance of this work is that it shows the possibility of real-time calculation of the electric field from the patient MRI and coordinates for the antenna, making it possible to optimize the amplitude, phase, and location of several different transducers with stochastic gradient descent since our model is a continuous function. Our work shows the potential of EMvelop stimulation to be portable, discreet, and continuously operable brain stimulation technology while being minimally invasive. The aim of our work is to expand the therapeutic options available to an even larger number of patients with neurological and psychiatric disorders.
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    Low-threshold, high-resolution, chronically stable intracortical microstimulation by ultraflexible electrodes
    (Cell Press, 2023) Lycke, Roy; Kim, Robin; Zolotavin, Pavlo; Montes, Jon; Sun, Yingchu; Koszeghy, Aron; Altun, Esra; Noble, Brian; Yin, Rongkang; He, Fei; Totah, Nelson; Xie, Chong; Luan, Lan; Bioengineering; Electrical and Computer Engineering; Rice Neuroengineering Initiative
    Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stable ICMS in awake, behaving mouse models. In vivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2 μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8 months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.
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    Minimally invasive reliable implantation of ultra-flexible electrodes for non-human primates
    (2023-11-28) Yip, Victor; Xie, Chong
    Ultra-flexible nanoelectric threads (NETs) have been successful in recording neural data in high densities in the cortical and sub-cortical regions, while avoiding post-surgery complications such as foreign-body responses or additional glial scarring from motion when compared to rigid electrodes. Studying sub-cortical brain function is important to understand lower-level brain activity and is mostly exclusive to microelectrodes that can be positioned close to the neurons of interest. To deliver the NET into the brain, a stiff shuttle is used to penetrate the brain tissue. The current T-shaped needle-and-thread shuttle has been successful for transdural implantation in rodents but struggles to scale to larger models. In this thesis, we intend to demonstrate the following: (1) The hook shuttle can be fabricated and successfully and reliably delivers NETs into the brain in rodent models. (2) The hook shuttle performs better than the T-shape shuttle by decreasing the required insertion force. (3) A cannula can be fabricated to help a shuttle deliver NETs into a non-human primate brain by reducing the required insertion force, demonstrated with parafilm and agarose gel phantoms.
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    Re-designing Cochlear Implants: A Multi-Helix High Electrode Density Prototype
    (2024-04-19) Acosta De Anda, Elsa; Xie, Chong
    Sensorineural hearing loss (SNHL) is the most prevalent type of hearing impairment, with approximately 66,000 new cases reported annually in the United States alone. Cochlear implants (CIs) have proven to be a successful technology, offering the possibility of auditory restoration for individuals affected by profound SNHL. However, despite their success, the performance of these prostheses has not been able to decode the intricate patterns of sound perception close to a natural level, struggling under noise conditions and being incapable of providing pure tonal perception. Therefore, the quest to achieve a higher resolution and stimulation specificity remains an open challenge. Aiming to increase the number of effective frequency channels for stimulation, development initiatives have brought the number of electrodes from one, in the first FDA-approved prototype, up to 24 stimulation sites in the most modern commercial implant. However, it has been reported that with straight electrodes, even when 22 electrodes were in place, the effective number of stimulation channels was only up to 8, after this threshold the improvement in performance plateaus. This limitation is primarily attributed to channel shunting caused by the current dispersion within the highly conductive cochlear fluid. Consequently, mitigating current spread is crucial to avoid simultaneous excitation of neighboring frequencies and prevent media saturation. In response to these challenges, this research introduces a novel prototype, addressing the limitations of conventional cochlear implants by increasing the number of electrodes while simultaneously mitigating the current spread. The proposed design includes ten times more electrodes than any currently available commercial implant. By augmenting the electrode density while also promoting a close implant-neuron interface, the prototype aims to enhance the resolution and frequency specificity of cochlear implant stimulation. This innovative approach represents a promising advancement in cochlear implant technology, offering the potential for higher quality auditory restoration and improved outcomes for individuals suffering from sensorineural hearing loss.
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    Ultraflexible neural electrode: advanced application in central and peripheral nervous systems
    (2020-12-01) Li, Xue; Xie, Chong
    As the ‘golden standard’ tools in neuroscience, electrophysiology recording affords the advantages of high temporal resolution detection of the neural signal. However, the conventional neural interface has been limited by its instability caused by the mechanical mismatch between the rigid electrode and the soft brain tissue. The ultraflexible neural interface development has enabled a glial-scare free, chronic stable, and multichannel neural interface in the rodent model for over many months. In this work, I further explore applying the ultraflexible neural electrode in both central and peripheral nervous systems. In the central nervous system, neural circuits span diverse spatial scales: they include different types of neurons organized in both nearby clusters and distributed brain regions. Conventional electrodes have limited spatial resolution and spatial coverage due to their high invasiveness and relatively large volume. In this work, we developed two methods to increase spatial resolution and broaden the spatial coverage. First, The scale-up of the ultraflexible neural electrodes enabled both dense volumetric recording and simultaneous large-scale recordings in the same brain, potentially achieving cellular-level functional connectome construction and precise behavior decoding in a chronic setup. Secondly, the combination of the ultraflexible neural interface with cortex-wide cranial window has enabled recording from individual neurons and simultaneous optical imaging in the neocortex for chronic studies. We show that this setting flexibly allows for the concurrent implementation of multiple neural recording and modulation techniques, including spatially resolved recordings at multiple regions and in deep structures, epi-fluorescence imaging across the cortex, two-photon imaging at multiple cortical regions, and optogenetics. In the peripheral nervous system, there are numerous demands for developing high channel count, chronic stable neural interface dependent neuroprosthesis. However, the existed neural interface still lacks the high specificity, high channel count, and chronic stable recording and stimulation capability that a complex neurophtosthesis requires. In this work, we developed two types of peripheral ultraflexible neural probes that can potentially achieve the chronic stable recording with high specificity and high channel count in the peripheral nervous system.
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    Ultraflexible Neural Electrodes for Long-Lasting Intracortical Recording
    (Cell Press, 2020) He, Fei; Lycke, Roy; Ganji, Mehran; Xie, Chong; Luan, Lan; NeuroEngineering Initiative
    Implanted electrodes provide one of the most important neurotechniques for fundamental and translational neurosciences by permitting time-resolved electrical detection of individual neurons in vivo. However, conventional rigid electrodes typically cannot provide stable, long-lasting recordings. Numerous interwoven biotic and abiotic factors at the tissue-electrode interface lead to short- and long-term instability of the recording performance. Making neural electrodes flexible provides a promising approach to mitigate these challenges on the implants and at the tissue-electrode interface. Here we review the recent progress of ultraflexible neural electrodes and discuss the engineering principles, the material properties, and the implantation strategies to achieve stable tissue-electrode interface and reliable unit recordings in living brains.