A combination of fMRI and Granger causality methods to study the effects of anesthesia on brain functional connectivity.
Introduction:
Anesthesia has to be applied in animal fMRI studies interfering with functional signals. A step further to understanding its effects on brain function is to analyze the connectivity between activated areas under different anesthetics. Granger Causality Mapping (GCM) can be used for this purpose. In this work we combine GCM and BOLD techniques to better understand the effects of anesthesia on brain function.
Methods:
Animal preparation: Four different groups of Sprague Dawley rats (n>10) were anaesthetized during the experiment with four different anesthetics: Isofluorane (ISO: air mix of 450O2 + 350N20 ml/min), Isofluorane+N2O (N2O: air mix of 450O2 + 550N2O ml/min), Rompun/Ketanest (RK: i.p. injection, 5mg/kg Rompun + 75mg/Kg Ketanest), and Trapanal (TRA: 1ml i.p. injection of 6% Trapanal). Paradigm: Heat was applied with a peltier element to the left hindpaw for four different heat stimuli (45,50,55 and 60°C). fMRI: Whole brain volumes were acquired with a 4.7T Bruker magnet with a quadrature surface coil. fMRI data was acquired with a GE-EPI sequence (2 excitations, TE effect=24.4 ms, TR=4s, in-plane resolution 400×400 μm, 1 mm slice thickness). Preprocessing and GLM analysis was performed with BrainVoyager after preprocessing. Home programmed software (under IDL) was used to calculate average BOLD signal of different functional groups formed by brain structures associated with somatosensory and pain circuits.GCM maps: GCM maps were obtained with a Matlab toolbox (Mathworks, Natick, MA) developed by A.K. Seth. Data fulfilled the stationary covariance requisite. Number of lags used (measurements prior to time 0) was 2.
Results:
Figure 1 presents % BOLD activation for the four different anesthetics in 11 different functional groups of the rat brain. Figure 2 presents the connections broken by anesthetics during pain processing for the right brain hemisphere. TRA showed the maximal total number of connections (in + out) (307,5 in average) followed by N2O (255), ISO(259) and RK (178.5).
Discussion:
BOLD discussion: BOLD responses are larger for the trapanal than for the other three anesthetics. The two isofluorane regimes are similar in % signal and RK shows the least BOLD response. There is a correlation between number of connections total BOLD intensity (R2=0.94)
GCM discussion: Thalamic-cortical connections together with inter-cortical connections are the most affected by anesthetic regimes. Lateral thalamus is blocked for RK and TRA. Information flow also appears blocked in right SI for TRA, N20 and RK. We hypothesize that it is in these regions where anesthetic affects information flow the most. All anesthetic regimes show a drop of connectivity in brain stem structures before reaching thalamic structures. N2O and TRA block information from motor cortex back into brain stem structures. Our connectivity assessment is limited by our analysis technique. We are unable to distinguish between direct interactions and connectivity mediated through a intermediate region. The utilization of techniques involving the spectral analysis of data can solve this problem eliminating these interactions (i.e. dDTF matrix).
Acknowledgements:
DFG (FG 661/TP4), BMBF (01EM0514, 01GQ0731, 0314102) and the Doerenkamp Foundation for Innovations in Animal and Consumer Protection.
Conference:
Neuroinformatics 2009, Pilsen, Czechia, 6 Sep - 8 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuroimaging
Citation:
De Celis Alonso
B,
Metzger
E,
Sergejeva
M and
Hess
A
(2019). A combination of fMRI and Granger causality methods to study the effects of anesthesia on brain functional connectivity..
Front. Neuroinform.
Conference Abstract:
Neuroinformatics 2009.
doi: 10.3389/conf.neuro.11.2009.08.019
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Received:
21 May 2009;
Published Online:
09 May 2019.
*
Correspondence:
Benito De Celis Alonso, FAU Erlangen, Nuremberg, Germany, benileon@yahoo.com