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72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

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Network activity in human cortical tissue recordings on micro-electrode arrays – a potential window to cortical micro-connectivity in normal and pathological human brain

Netzwerkaktivität in humanem Kortexgewebe in Mikro-Elektroden Array Recordings – ein potentielles Fenster zu kortikaler Mikrokonnektivität in gesundem und pathologischem Hirngewebe

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  • presenting/speaker Jonas Ort - Universitätsklinikum Aachen, Klinik für Neurochirurgie, Aachen, Deutschland; Universitätsklinikum Aachen, Neurosurgical Artificial Intelligence Laboratory Aachen (NAILA), Aachen, Deutschland
  • Jenny Wickham - University of Tübingen, Neurophysics, Natural and Medical Sciences Institute, Reutlingen, Deutschland
  • Aniella Bak - Universitätsklinikum Aachen, Department of Epileptology, Neurology, Aachen, Deutschland
  • Andrea Corna - University of Tübingen, Neurophysics, Natural and Medical Sciences Institute, Reutlingen, Deutschland
  • Julia Schmierer - University of Tübingen, Neurophysics, Natural and Medical Sciences Institute, Reutlingen, Deutschland
  • Thomas Wuttke - University of Tübingen, Department of Neurosurgery, Tübingen, Deutschland; University of Tübingen, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Deutschland
  • Niklas Schwarz - University of Tübingen, Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tübingen, Deutschland
  • Hans Clusmann - Universitätsklinikum Aachen, Klinik für Neurochirurgie, Aachen, Deutschland
  • Yvonne Weber - Universitätsklinikum Aachen, Department of Epileptology, Neurology, Aachen, Deutschland
  • Daniel Delev - Universitätsklinikum Aachen, Klinik für Neurochirurgie, Aachen, Deutschland; Universitätsklinikum Aachen, Neurosurgical Artificial Intelligence Laboratory Aachen (NAILA), Aachen, Deutschland
  • Günther Zeck - University of Tübingen, Neurophysics, Natural and Medical Sciences Institute, Reutlingen, Deutschland
  • Henner Koch - Universitätsklinikum Aachen, Department of Epileptology, Neurology, Aachen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP098

doi: 10.3205/21dgnc386, urn:nbn:de:0183-21dgnc3865

Published: June 4, 2021

© 2021 Ort et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Micro-Electrode Arrays (MEAs), novel culturing methods for human brain tissue, and advanced tools in data science enable us for the first time to analyze massive parallel recordings of spike trains in human cortical tissue. Measuring neuronal connectivity on a millimeter scale in real time can help us to understand cortical microcircuits. Here we recorded human tissue of neurosurgical interventions in vitro on MEAs to investigate spatio-temporal patterns (STP) in spiking activity.

Methods: Organotypic human cortical slices were prepared from tissue resected from epilepsy patients undergoing surgical treatment. Slices were cultivated as described (Wickham et al. 2020) and the optogenetic actuator Channelrhodopsin-2 was transduced into the slices for specific stimulation. Recordings were obtained using a 256-MEA (electrode spacing: 200µm) combined with optogenetic stimulation. Data analysis was performed using Python including packages numpy, elephant, neo and viziphant. Bursts were detected using an interspike-interval method. Spiketrains were analyzed for STP using SPADE (“Spike Pattern Detection and Evaluation”) with a minimum of 30 instances and 3 spikes to qualify as pattern on one exemplary recording (120 seconds). We investigated for optogenetic-induced patterns and spontaneous activity.

Results: On multiple recordings we found massive network bursts with a spatial extent of several 100µm that lasted for seconds seemingly independent of optogenetic stimulation. We detected >80.000 spiking patterns. Specific patterns only observed during network bursts appeared >90 times and could be found with a spatial extent up to 1.8 mm and latency times of 130ms (SPADE p-value=0.047), thus indicating a robust polysynaptic neuronal connection possibly explaining distant tissue epileptogenic micro-foci.

Conclusion: Within network bursts we identified several spatio-temporal patterns with remarkable spatial extent and latencies between spikes. This method is a promising tool for investigations of electrophysiological features of cerebral pathologies such as epilepsy or glioma. These features potentially reveal novel aspects of pathogenesis. Next steps will be to integrate these physiological findings into histo(patho)logical context.