The Five Trolls Under the Bridge: Principal Component Analysis with Asynchronous and Noisy High Frequency Data

2018 ◽  
Author(s):  
Dachuan Chen ◽  
Per A. Mykland ◽  
Lan Zhang
Keyword(s):  
Principal Component Analysis ◽  
High Frequency ◽  
Principal Component ◽  
Component Analysis ◽  
High Frequency Data ◽  
Frequency Data

scholarly journals Collapse of Global Neuronal States in Caenorhabditis elegans under Isoflurane Anesthesia

2020 ◽  
Vol 133 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Mehraj R. Awal ◽  
Gregory S. Wirak ◽  
Christopher V. Gabel ◽  
Christopher W. Connor
Keyword(s):  
Principal Component Analysis ◽  
Caenorhabditis Elegans ◽  
Neuronal Activity ◽  
High Frequency ◽  
Dynamic Range ◽  
Functional Organization ◽  
Principal Component ◽  
Component Analysis ◽  
C Elegans ◽  
Light Sheet Microscopy

Background A comprehensive understanding of how anesthetics facilitate a reversible collapse of system-wide neuronal function requires measurement of neuronal activity with single-cell resolution. Multineuron recording was performed in Caenorhabditis elegans to measure neuronal activity at varying depths of anesthesia. The authors hypothesized that anesthesia is characterized by dyssynchrony between neurons resulting in a collapse of organized system states. Methods Using light-sheet microscopy and transgenic expression of the calcium-sensitive fluorophore GCaMP6s, a majority of neurons (n = 120) in the C. elegans head were simultaneously imaged in vivo and neuronal activity was measured. Neural activity and system-wide dynamics were compared in 10 animals, progressively dosed at 0%, 4%, and 8% isoflurane. System-wide neuronal activity was analyzed using principal component analysis. Results Unanesthetized animals display distinct global neuronal states that are reflected in a high degree of correlation (R = 0.196 ± 0.070) between neurons and low-frequency, large-amplitude neuronal dynamics. At 4% isoflurane, the average correlation between neurons is significantly diminished (R = 0.026 ± 0.010; P < 0.0001 vs. unanesthetized) and neuron dynamics shift toward higher frequencies but with smaller dynamic range. At 8% isoflurane, interneuronal correlations indicate that neuronal activity remains uncoordinated (R = 0.053 ± 0.029; P < 0.0001 vs. unanesthetized) with high-frequency dynamics that are even further restricted. Principal component analysis of unanesthetized neuronal activity reveals distinct structure corresponding to known behavioral states. At 4% and 8% isoflurane this structure is lost and replaced with randomized dynamics, as quantified by the percentage of total ensemble variance captured by the first three principal components. In unanesthetized worms, this captured variance is high (88.9 ± 5.4%), reflecting a highly organized system, falling significantly at 4% and 8% isoflurane (57.9 ± 11.2%, P < 0.0001 vs. unanesthetized, and 76.0 ± 7.9%, P < 0.001 vs. unanesthetized, respectively) and corresponding to increased randomization and collapse of system-wide organization. Conclusions Anesthesia with isoflurane in C. elegans corresponds to high-frequency randomization of individual neuron activity, loss of coordination between neurons, and a collapse of system-wide functional organization. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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