Reconciling functional differences in populations of neurons recorded with two-photon imaging and electrophysiology

Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measuring physiological activity with single cell resolution across large populations of neurons in the brain. While these two modalities have distinct advantages and disadvantages, neither provides complete, unbiased information about the underlying neural population. Here, we compare evoked responses in visual cortex recorded in awake mice under highly standardized conditions using either imaging or electrophysiology. Across all stimulus conditions tested, we observe a larger fraction of responsive neurons in electrophysiology and higher stimulus selectivity in calcium imaging. This work explores which data transformations are most useful for explaining these modality specific discrepancies. We show that the higher selectivity in imaging can be partially reconciled by applying a spikes-to-calcium forward model to the electrophysiology data. However, the forward model could not reconcile differences in responsiveness without sub selecting neurons based on event rate or level of signal contamination. This suggests that differences in responsiveness more likely reflect neuronal sampling bias or cluster merging artifacts during spike sorting of electrophysiological recordings, rather than flaws in event detection from fluorescence time series. This work establishes the dominant impacts of the two modalities9 respective biases on a set of functional metrics that are fundamental for characterizing sensory-evoked responses.R01 EB026908 - NIBIB NIH HHShttps://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8285106&blobtype=pdfPublished versio

High-Resolution μECoG: Design, Fabrication, and Applications

Since the early 1950s, electrocorticography (ECoG), the measurement of electrical potentials on the surface of the brain has become an invaluable tool in neurosurgery for the localization of epileptic foci before resection. The ECoG electrodes used in clinical practice are made in an archaic serial process that involves hand-soldering wires to a stiff, coarse grid of electrodes with a spatial resolution >1 cm, and a tangle of transcranial wires. In this thesis we report a modern microfabrication process based on photolithographic patterning of conductor thin films and of Parylene C, a biocompatible, transparent polymer. We used that process to make very thin and flexible ECoG arrays with electrode densities exceeding those of their clinical counterparts by more than two orders of magnitude, and addressed interconnect and noise performance issues. We constructed devices with multiple interconnected conductor layers, and used transparent conductors for integration of ECoG with optical neural stimulation techniques. Moreover, we developed a microscale ECoG with integrated loop antenna for a fully implantable, wireless system. To show that such high-resolution devices have practical utility, we conducted acute and chronic in vivo studies in rats. We found that sufficiently small ECoG electrodes were able to register superficial multi-unit activity. We computed high-resolution tonotopic maps of the auditory cortex in anesthetized rats, and demonstrated that functional mapping using signal power in the 70 Hz - 170 Hz band (high-&gamma) is consistent with but much quicker and often more robust than functional mapping using action potentials recorded intracortically with penetrating electrodes. Finally we demonstrated that &muECoG can serve as a less invasive alternative to penetrating electrodes in a brain-machine interface (BMI) paradigm by training awake behaving rats, chronically implanted with &muECoG, to perform a 1D center-out task with auditory feedback by differentially modulating the high-&gamma signal on electrodes separated by as little as 200 &mum

High performance light emitting transistors

Solution processed light emitting field-effect transistors (LEFETs) with peak brightness exceeding 2500 cd m2 and external quantum efficiency of 0.15% are demonstrated. The devices utilized a bilayer film comprising a hole transporting polymer, poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2- b] thiophene) and a light emitting polymer, Super Yellow, a polyphenylenevinylene derivative. The LEFETs were fabricated in the bottom gate architecture with top-contact CaAg as source/drain electrodes. Light emission was controlled by the gate voltage which controls the hole current. These results indicate that high brightness LEFETs can be made by using the bilayer film (hole transporting layer and a light emitting polymer)

Grid-Based Spectral Fiber Clustering

We introduce novel data structures and algorithms for clustering white matter fiber tracts to improve accuracy and robustness of existing techniques. Our novel fiber grid combined with a new randomized soft-division algorithm allows for defining the fiber similarity more precisely and efficiently than a feature space. A fine-tuning of several parameters to a particular fiber set- as it is often required if using a feature space- becomes obsolete. The idea is to utilize a 3D grid where each fiber point is assigned to cells with a certain weight. From this grid, an affinity matrix representing the fiber similarity can be calculated very efficiently in time O(n) in the average case, where n denotes the number of fibers. This is superior to feature space methods which need O(n 2) time. Our novel eigenvalue regression is capable of determining a reasonable number of clusters as it accounts for inter-cluster connectivity. It performs a linear regression of the eigenvalues of the affinity matrix to find the point of maximum curvature in a list of descending order. This allows for identifying inner clusters within coarse structures, which automatically and drastically reduces the a-priori knowledge required for achieving plausible clustering results. Our extended multiple eigenvector clustering exhibits a drastically improved robustness compared to the wellknown elongated clustering, which also includes an automatic detection of the number of clusters. We present several examples of artificial and real fiber sets clustered by our approach to support the clinical suitability and robustness of the proposed techniques

Columnar Localization and Laminar Origin of Cortical Surface Electrical Potentials.

Electrocorticography (ECoG) methodologically bridges basic neuroscience and understanding of human brains in health and disease. However, the localization of ECoG signals across the surface of the brain and the spatial distribution of their generating neuronal sources are poorly understood. To address this gap, we recorded from rat auditory cortex using customized μECoG, and simulated cortical surface electrical potentials with a full-scale, biophysically detailed cortical column model. Experimentally, μECoG-derived auditory representations were tonotopically organized and signals were anisotropically localized to less than or equal to ±200 μm, that is, a single cortical column. Biophysical simulations reproduce experimental findings and indicate that neurons in cortical layers V and VI contribute ∼85% of evoked high-gamma signal recorded at the surface. Cell number and synchrony were the primary biophysical properties determining laminar contributions to evoked μECoG signals, whereas distance was only a minimal factor. Thus, evoked μECoG signals primarily originate from neurons in the infragranular layers of a single cortical column.SIGNIFICANCE STATEMENT ECoG methodologically bridges basic neuroscience and understanding of human brains in health and disease. However, the localization of ECoG signals across the surface of the brain and the spatial distribution of their generating neuronal sources are poorly understood. We investigated the localization and origins of sensory-evoked ECoG responses. We experimentally found that ECoG responses were anisotropically localized to a cortical column. Biophysically detailed simulations revealed that neurons in layers V and VI were the primary sources of evoked ECoG responses. These results indicate that evoked ECoG high-gamma responses are primarily generated by the population spike rate of pyramidal neurons in layers V and VI of single cortical columns and highlight the possibility of understanding how microscopic sources produce mesoscale signals

Design of Wireless Links to Implanted Brain-Machine Interface Microelectronic Systems

This article presents a monolithic integration of an antenna with an array of neural recording electrodes on a flexible thin-film. The structure was designed for long-term neural recording in a wireless brain-machine interface system. The implant – on-body antenna pair is optimized for maximal link power efficiency to maximize the battery-life of a portable outside-body control unit. We provide guidelines for the design of the sub-skin-depth implant antenna and validate the antenna simulation model with wireless link measurements in air. We propose a new computational analysis of both the power and voltage delivery to the battery-free implant under design variations to guarantee efficient on-chip RF-to-DC conversion.acceptedVersionPeer reviewe