Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.
We developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are cultured and from which propagation of extracellular action potentials (eAPs) in single axons are recorded at multiple electrodes. Detecting eAP propagation bypasses ambiguity introduced by spike sorting. Our methods identify short latency spiking relationships between neurons with properties expected of synaptically coupled neurons, namely they were recapitulated by direct stimulation and were sensitive to changing the number of active synaptic sites. Our methods enabled us to assemble a functional subset of neuronal connectivity in our cultures.
Chronic pain is defined as pain that lasts or recurs for more than 3 to 6 months, often long after the injury or illness that initially caused the pain has healed. The gold standard for chronic pain assessment remains self report and clinical assessment via a biopsychosocial interview, since there has been no device that can measure it. A device to measure pain would be useful not only for clinical assessment, but potentially also as a biofeedback device leading to pain reduction. In this paper we propose an end-to-end deep learning framework for chronic pain score assessment. Our deep learning framework splits the long time-course data samples into shorter sequences, and uses Consensus Prediction to classify the results. We evaluate the performance of our framework on two chronic pain score datasets collected from two iterations of prototype Pain Meters that we have developed to help chronic pain subjects better understand their health condition.
Multi-Electrode Arrays (MEAs) have been widely used to record neuronal activities, which could be used in the diagnosis of gene defects and drug effects. In this paper, we address the problem of classifying in vitro MEA recordings of mouse and human neuronal cultures from different genotypes, where there is no easy way to directly utilize raw sequences as inputs to train an end-to-end classification model. While carefully extracting some features by hand could partially solve the problem, this approach suffers from obvious drawbacks such as difficulty of generalizing. We propose a deep learning framework to address this challenge. Our approach correctly classifies neuronal culture data prepared from two different genotypes -a mouse Knockout of the delta-catenin gene and human induced Pluripotent Stem Cell-derived neurons from Williams syndrome. By splitting the long recordings into short slices for training, and applying Consensus Prediction during testing, our deep learning approach improves the prediction accuracy by 16.69% compared with feature based Logistic Regression for mouse MEA recordings. We further achieve an accuracy of 95.91% using Consensus Prediction in one subset of mouse MEA recording data, which were all recorded at six days in vitro. As high-density MEA recordings become more widely available, this approach could be generalized for classification of neurons carrying different mutations and classification of drug responses.
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