Joanes Grandjean1, Maria G. Preti 2,3, Thomas AW Bolton2, Dimitri Van De Ville2, and Markus Rudin4
1ETH and University Zurich, Zurich, Switzerland, 2EPFL, Lausanne, Switzerland, 3University of Geneva, Geneva, Switzerland, 4University and ETH Zurich, Zurich, Switzerland
Synopsis
Dynamic functional connectivity was
assessed in the mouse brain. High quality resting-state fMRI data were acquired
and analysed with sliding window correlations. Re-occurring dynamic functional
networks were estimated using dictionary learning from the sliding window
correlation matrix. The dynamic
functional connectivity analysis reveals rich patterns of interactions, which
were absent in the standard static functional connectivity analysis, and may be
used to describe specific alterations in mouse models of brain disorders. In
particular, the dynamic functional networks present salient features such as
between and within module interactions, which complement the static functional
connectivity analysis. Introduction
Brain activity is a highly dynamic process
across different temporal and spatial scales. The control of cognition and
behaviour relies on computations performed at different location in the brain,
and relies on the integration of complex information. Resting-state fMRI has
been proposed to resolve the functional connectome of the brain in an effort to
understand function in the healthy and disordered brain. However, while the brain is highly dynamic,
the vast majority of the resting-state fMRI data analysis relies on the
stationary assumption, i.e. a constant interaction between region pairs over
the duration of the recording. Here, we
investigated the dynamic functional networks of the anesthetised mouse brain.
We used sliding window correlation to estimate the dynamics between any region
pairs, and dictionary learning to perform dimensionality reduction to obtain a
set of 20 reproducible dynamic functional networks.
Method
C57BL/6 mice were anesthetized with
isoflurane 0.5% and medetomidine 0.05mg/kg bolus and 0.1mg/kg/h infusion as in (Grandjean et al., 2014). Functional imaging took place on a 9.4 Bruker biospec with a
linear volume coil for excitation and a 2x2 phased-array receiver cryogenic
coil. Multi-echo gradient-echo EPI were acquired with TE=11, 17, 23ms,
TR=1500ms, FA=60°, 600 volumes, and an in plane resolution of 0.3mm². ME-EPI
were reconstructed and denoised using meica.py script (Kundu et al., 2012) (AFNI, http://afni.nimh.nih.gov/)
, and coregistered to the AMBMC mouse template. Independent component analysis
was performed to parcellate the brain using Melodic with 30 components (FSL, http://fsl.fmrib.ox.ac.uk/). The
components identified were further separated between hemispheres. A static
functional network was reconstructed from the signal from 12 selected components.
Louvain algorithm for weighted networks was used to identify 3 modules, a
sub-cortical network (SuCN), a lateral cortical network (LCN), and a set of
regions related to the default mode network (DMN). Sliding window correlation (SWC)
with window size =30, and step size =2, was used to estimate the changes in
correlations between region pairs over time. The SWC matrix was demeaned, and
detrended with third order polynomials. Dictionary learning algorithm with 30
folds each made of 200 iterations was used to estimate simple building blocks
of whole-brain connectivity, the atoms. The patterns thus extracted explained
50% of the variance in the SWC matrix.
Results
Static functional connectivity of the
ICA-parcellated mouse brain indicate strongest pattern of correlations between
inter-hemispheric homotopic region pairs (Figure 1: e.g. left to right anterior
parietal cortex; aPc). The regions could be organized into 3 distinct modules,
the sub-cortical network (SuCN) including the dorsal, ventral, and lateral
striatum (dStr, vStr, lStr) and anterior parietal cortex (aPc), the lateral
cortex network (LCN) including the medial and posterior parietal cortex (mPc,
pPc), and motor cortex (Mc), and finally a default mode network (DMN) which
included the prefrontal cortex (PFC), the cingulate/retrosplenial cortex
(Cg/Rs), dorsal and ventral hippocampus (dHc, vHc), and thalamus. Dynamic
functional networks were estimated using dictionary learning, a set of 20 atoms
were estimated and accounted for 50% of the total variance of the SWC (Fig 2).
The patterns revealed interactions, in particular between and within the
modules, for instance atom #3 indicate interactions between the LCN and the
SuCN, while atom #14 indicates interactions within the SuCN. Further, the
thalamus is highlighted in atom #17, while there was little evidence of static
interactions between the thalamus and the other regions (Fig 1). Finally the
atoms presented high values of similarities between the different folds of the
dictionary learning process, underlying the reproducibility of the atoms
estimated (Fig 3).
Discussion
Dynamic functional connectivity analysis in the
mouse brain is highly attractive due to its relative simple architecture as
compared to humans, but also in the light of the many transgenic lines
available. Here we show that estimation of dynamic functional networks reveals
rich patterns of interactions masked in the standard static connectivity
analysis. Moreover, the patterns highlighted in the mouse present salient features,
such as between and within modules groups of interactions, which may indeed
represent crucial elements necessary for the segregation and integration of
information, which are necessary for brain computation. The mouse is a model of
choice to investigate the nature and mechanisms underlying dynamic functional
networks in the healthy brain, as well as in the many murine models of brain
disorders.
Acknowledgements
No acknowledgement found.References
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