title: Joint analysis of extracellular spike waveforms and neuronal network bursts.
abstract: BACKGROUND
  Neuronal networks are routinely assessed based on extracellular electrophysiological microelectrode array (MEA) measurements by spike sorting, and spike and burst statistics. We propose to jointly analyze sorted spikes and detected bursts, and hypothesize that the obtained spike type compositions of the bursts can provide new information on the functional networks.
  
  
  METHODS
  Spikes are detected and sorted to obtain spike types and bursts are detected. In the proposed joint analysis, each burst spike is associated with a spike type, and the spike type compositions of the bursts are assessed.
  
  
  RESULTS
  The proposed method was tested with simulations and MEA measurements of in vitro human stem cell derived neuronal networks under different pharmacological treatments. The results show that the treatments altered the spike type compositions of the bursts. For example, 6-cyano-7-nitroquinoxaline-2,3-dione almost completely abolished two types of spikes which had composed the bursts in the baseline, while bursts of spikes of two other types appeared more frequently. This phenomenon was not observable by spike sorting or burst analysis alone, but was revealed by the proposed joint analysis.
  
  
  METHODS
  The existing methods do not provide the information obtainable with the proposed method: for the first time, the spike type compositions of bursts are analyzed.
  
  
  CONCLUSIONS
  We showed that the proposed method provides useful and novel information, including the possible changes in the spike type compositions of the bursts due to external factors. Our method can be employed on any data exhibiting sortable action potential waveforms and detectable bursts.
authors.affiliation: Tampere University of Technology, Department of Electronics and Communications Engineering, Computational Biophysics and Imaging Group, BioMediTech, Biokatu 6, FI-33520 Tampere, Finland. Electronic address: fikret.kapucu@tut.fi.
authors.forename: Fikret Emre
authors.initials: FE
authors.lastname: Kapucu
authors.affiliation: University of Tampere, NeuroGroup, BioMediTech, Biokatu 12, FI-33014 Tampere, Finland. Electronic address: meeri.makinen@uta.fi.
authors.forename: Meeri E-L
authors.initials: ME
authors.lastname: Mäkinen
authors.affiliation: Tampere University of Technology, Department of Electronics and Communications Engineering, Computational Biophysics and Imaging Group, BioMediTech, Biokatu 6, FI-33520 Tampere, Finland. Electronic address: tanskanen@ieee.org.
authors.forename: Jarno M A
authors.initials: JMA
authors.lastname: Tanskanen
authors.affiliation: University of Tampere, NeuroGroup, BioMediTech, Biokatu 12, FI-33014 Tampere, Finland. Electronic address: laura.yla-outinen@uta.fi.
authors.forename: Laura
authors.initials: L
authors.lastname: Ylä-Outinen
authors.affiliation: University of Tampere, NeuroGroup, BioMediTech, Biokatu 12, FI-33014 Tampere, Finland. Electronic address: susanna.narkilahti@uta.fi.
authors.forename: Susanna
authors.initials: S
authors.lastname: Narkilahti
authors.affiliation: Tampere University of Technology, Department of Electronics and Communications Engineering, Computational Biophysics and Imaging Group, BioMediTech, Biokatu 6, FI-33520 Tampere, Finland. Electronic address: jari.hyttinen@tut.fi.
authors.forename: Jari A K
authors.initials: JAK
authors.lastname: Hyttinen
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena / Q000187:drug effects* / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology*; D058953:Neural Stem Cells; D012815:Signal Processing, Computer-Assisted
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione
keywords: Burst detection; Electrophysiological signal analysis; Microelectrode array; Neuronal network; Spike sorting; Spike waveform