Browsing by Author "Luan, Lan"

Now showing 1 - 8 of 8
  • Thumbnail Image
    Item
    Illuminating Neocortical-Hippocampal Interactions - Elucidating Widefield Cortical Dynamics of Sensory Cue Processing during Sharp-Wave Ripple Events
    (2023-10-11) Noble, Brian Christopher; Luan, Lan; Szablowski , Jerzy
    Sensory cue consolidation is critical for the survival of animals, involving a variety of neural processes occurring in multiple brain regions. On a mesoscale, different Ca2+ reactivation patterns manifest across the neocortex when learning new sensory cues, while changes in task-related neuronal assembly between the prefrontal and hippocampus are observed during awake sharp-wave ripple (SWR) events, which play a crucial role in consolidation. Despite these insights, the wide-scale correlations between different brain regions during hippocampal activity following sensory stimulation remain poorly understood. To bridge this gap, we conducted a multimodal study using co-implantation of a near-cortex wide polymer window and longitudinal neural nanoelectronic threads (NETs) implanted in the CA1 of the hippocampus. By simultaneously recording neocortical-hippocampal activity during periods of visual stimulation and non-stimulation, our goal was to elucidate the correlations between multiple brain regions during hippocampal activity, specifically awake SWRs, in both visual and non-visual stimulation epochs. We mapped the different Ca2+ correlations between 28 cortical regions during a sharp wave ripple event in sequential periods of visual stimulation and zero-stimulus stimulation. Our findings revealed that during an SWR event, all brain regions exhibit changes in their correlation coefficients with one another in pre-visual versus post-visual zero-stimulus stimulation periods. Most notably, the pre-motor and visual regions of the neocortex display the largest change in correlation (α < 0.05) with all other brain regions during post-visual and pre-visual zero-stimulation stages. Furthermore, the sum of all correlations for each brain region and their eigen-centrality become more significant in post-visual zero-stimulus periods compared to pre-visual zero visual stimulation. These results suggest that distinct functional dynamics emerge between different brain regions during an SWR event in a period of no stimulation after visual stimulation. This has significant implications for future research on the mechanisms underlying sensory perception and the roles of various brain regions in this process. Additionally, our innovative approach using co-implantation of a near-cortex wide polymer window and NETs in a visual regime offers a potent tool for simultaneously investigating neural activity across multiple brain regions during sensory processing.
  • Thumbnail Image
    Item
    Longitudinal behavioral detectability and selective neural activation evoked by low current intracortical microsimulation using ultra-flexible electrodes
    (2022-12-02) Kim, Robin; Luan, Lan
    Studies on human patients have allowed better understanding of the conscious sensations associated with ICMS (intracortical microstimulation) in hopes of restoring sensory functions. An effective clinical neuro- prosthetic should manipulate neural activity at a high spatial resolution, minimize charge injection, and demonstrate chronic stability. In this thesis, we propose that the Stimulating NanoElectronic Threads (StimNETs) possess these attributes by examining and providing experiment evidence for the following three research goals: (1) Using two-photon (2P) calcium imaging of awake animals, we visualized and verified selective neuronal activation patterns under low-current ICMS. (2) To evaluate the behavioral effects of ICMS, we designed a go/no-go detection threshold task and observed thresholds as little as 0.25 nC/phase. (3) To show that stim-NETs are chronically stable, we present longitudinal data with the longest behavioral performing animal 10 months post-implantation. These results show that tissue-integrated ultraflexible electrodes provide high-resolution, efficacy, and stability in neuromodulation.
  • Thumbnail Image
    ItemEmbargo
    Longitudinal study of stroke-induced neuroplasticity using imaging and high-density neural recording
    (2024-08-09) Rathore, Haad; Luan, Lan
    The brain has a remarkable ability to undergo spontaneous self-repair in response to an injury or a cortical lesion. This dynamic and lasting restorative process involves a diverse array of neuroplastic mechanisms that are time and location dependent. Lesion-induced neuroplasticity is believed to involve neighboring intact neurons assuming the functional roles of the damaged ones, altering the brain’s activation map. Despite extensive research, there is still a lack of definitive evidence regarding neurons changing their functional response, leading to debates about the exact cellular mechanism of neuroplasticity. Conclusive evidence supporting or refuting functional remapping after stroke requires direct measurements and longitudinal tracking of neural activity at a single-neuron resolution and over chronic periods. In this work, we employed multi-electrode arrays (NanoElectronic Threads) to record and longitudinally track both the sensory-evoked single-neuron spiking dynamics and population activity with high spatial specificity after a small-scale optically targeted stroke. Our multimodal measurement combined simultaneous laser speckle contrast imaging and hyperspectral reflectance spectroscopy, together with spatially distributed intracortical neural recordings. We found that while hemodynamic activation shifted following the cortical lesion, it no longer correlated with electrical neural activity. Direct neural recording showed a sustained suppression of evoked spiking activity near the lesioned infarct while an enhancement in the more distant cortical regions. Longitudinal tracking of individual neurons uncovered heterogeneous responses underlying the enhanced activity. We observed a distinct subset of neurons that demonstrated a significant upregulation in their sensory-evoked spiking activity which exhibited a stronger correlation with the overall population activity within the local cortical network, suggesting a potential restorative mechanism in response to the lesion. Contrary to the prevailing hypothesis of population-level changes in the peri-infarct region, our findings provide compelling evidence against this notion. Instead, our data reveal that lesion-induced plasticity at the single neuron level is manifested as a selective potentiation of pre-existing functional neurons.
  • Thumbnail Image
    ItemEmbargo
    Longitudinal tracking of neural vascular recovery post microinfarct using multimodal neural platform
    (2023-10-19) Jin, Yifu; Luan, Lan
    Ischemic stroke is a leading cause of morbidity and mortality worldwide, with hundreds of thousands of cases occurring annually. The disease is caused by the obstruction or reduction of blood flow to part of the brain, typically due to the buildup of cholesterol-containing fatty deposits called plaques in an artery or one of its branches. Microinfarcts are a milder form of ischemic stroke with tiny area of tissue damage resulting from blockage of small cerebral blood vessels such as arterioles and capillaries. In this study, we induced mini-scale photo-thrombotic strokes in aged mice to investigate how neural activities respond to such small-scale occlusion. We used ultra-flexible nanoelectrode thread probes, two-photon imaging, and speckle imaging to track neural activities, microvascular structure, and regional cerebral blood flow longitudinally post-stroke. Our findings reveal several important insights about this transient local damage in an aged mouse model. Firstly, we observed that neural activity near the infarct site recovers to baseline levels at the same pace as the capillary bed after mini-scale stroke induction. Secondly, our cell-type-specific analysis of single neurons revealed that the excitability of fast-spiking narrow interneurons is dampened the most among all cell types during this minor ischemic induction and recovery process. Thirdly, we found that neuronal damage is depth-related, with shallower layers being more severely affected than deeper layers. Lastly, our results suggest that spike phase locking at the low gamma band, which is dominant in the shallow cortical layer, is weakly but long-lastingly compromised, indicating an interruption in large-scale neuronal assembly communication. Overall, these findings shed light on the neurovascular impact of a photo-thrombosis microinfarct, including its effects on capillary structure, the response of individual neurons, and the functioning of large-scale neural networks.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    ItemEmbargo
    Multimodal longitudinal imaging to monitor neurovascular responses to brain injuries
    (2024-02-05) Sun, Yingchu; Luan, Lan
    The evolution of brain injury comprises diverse dynamic interactions between initial triggers of injury and evolutionarily conserved responses of brain plasticity, remodeling, and compensation. Altered neurovascular activity is critical endogenous responses to various brain injuries, which not only underlies the evolution of cascades of neuroinflammation and cell death but also simultaneously pave the way for recovery. Owing to the multifaceted nature of neurovascular interactions, simultaneously monitoring of neurons, vasculature, and other cells and neurotransmitters through these evolving events are necessary to provide comprehensive understanding of the impairment and recovery. Here we employ a multimodal platform that integrate various imaging techniques and electrophysiology to reveal the lasting, dynamic changes of neurovascular activity following two types of brain injuries: the intracortical implantation of a ultraflexible polymer electrode, and high-energy-density, short-pulsed microwave radiation. By integrating multiple imaging methods such as two-photon imaging, laser speckle contrast imaging and intrinsic optical imaging, we were able to bridge spatial resolution from sub-cellular to regional and detect alterations in multiple biomarkers including cerebral blood flow, microvasculature, and extracellular glutamate. In the first study, we find heightened angiogenesis and vascular remodeling in the first two weeks after implantation of flexible electrodes, which coincides with the rapid increase in local field potentials and unit activities detected by electrophysiological recordings. Vascular remodeling in shallow cortical layers preceded that in deeper layers, which often lasted longer than the recovery of neural signals. In the second study, we find that microwave radiation led to a suppression of glutamate release, which aligns with the decrease in local field potentials. Conversely, we noted a rise in cerebral blood flow during the stimulation. Although it seems that heating may contribute partially to this observed increase, it's essential to acknowledge that other mechanisms, such as the thermoelastic stress waves, have substantial impact as well. It is supported by the fact that pulsed microwave radiation affected cerebral blood flow differently compared to continuous microwave radiation. The deeper study also reveals that the focused ultrasound stimulation does not affect the glutamate release, neural activities and cerebral blood flow. Taking together, my study has effectively tracked both vascular remodeling and neural recovery following the ultraflexible neural electrode implantation over several weeks. And we also identified biological responses within seconds of the brain receiving microwave radiation and focused ultrasound stimulation. These efforts have paved the way for future interventions for neurovascular injuries and recovery.
  • Thumbnail Image
    ItemEmbargo
    Recording and stimulation of spinal interneurons in freely moving mouse using ultraflexible electrodes
    (2025-01-30) Zhang, Jiaao; Luan, Lan
    Intra-spinal microstimulation (ISMS) is a valuable tool for both scientists and engineers, offering mechanistic studies of the response characteristics of local spinal cord neurons and circuits in-vivo as well as potentials for high-resolution stimulation treatments of spinal cord injuries and other motor deficits. However, due to technological limitations, previous studies have mostly been conducted in anesthetized or highly constrained animals. This approach overlooks the dynamics of motor behaviors, which are integral to these applications and may influence the effect of ISMS on local spinal circuit. In this study, we investigate the effect of temporally synchronizing ISMS with natural behavioral states on the neural activation and behavioral outcome in the mouse lumbar cord. This study also contributes to understanding the spinal cord interneuron population dynamics from an electrophysiological point of view. We leverage ultraflexible intraspinal electrodes, the na- noelectronic threads (NETs), for concurrent recording and stimulation during unrestrained motor behaviors. We find that single pulse stimulation no greater than 2nC/phase elicited robust neu- ral activation. Stimulation of different channels along the dorsal-ventral axis yielded distinctive activation pattern and well-separated neuron-populational trajectories after dimensionality reduction of single-unit spiking activities, with mild day-to-day fluctua- tions and overall stability. Preliminary results suggest that the strength of modulation is dependent on the site of stimulation. Pulse-train stimulations elicited a spectrum of hind limb movements including stepping, limb flapping and muscle contraction at low currents with considerable trial-to-trial variability. In order to mitigate variability in pre-stimulation baseline neural state, we implement closed-loop stimulation using real-time behavioral markers, controlling the behavioral state for each stimulation. This paradigm will help reveal how the spinal cord neural circuitry along the dorsal-ventral axis reacts and adapts to perturbation during rhythmic activity. These ongoing efforts underscore the critical interplay between ISMS and behavior. Our study holds implications for advancing the stimulation paradigm for both basic scientific investigation and potential translational applications.
  • Thumbnail Image
    Item
    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.