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Table of contents
Acknowledgements ... 5
Résumé en français ... 6
Abbreviations ... 8
Abstract ... 10
1
Introduction and aims ... 13
1.1 Functional electrophysiological connectivity ... 13
1.2 Research questions and summaries ... 17
1.3 Outline ... 23
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From sources to sensors and back: Neuromagnetism and magnetoencephalography ... 25
2.2 Measuring brain activity with MEG ... 25
2.1.1 The neural origin of MEG signals ... 25
2.1.2 MEG hardware and function ... 30
2.1.3 Data acquisition procedure ... 31
2.3 Inferring brain activity from MEG data ... 32
2.2.1 Sensor-space and source-space ... 32
2.2.2 The forward problem ... 35
2.2.3 The inverse problem ... 36
2.2.4 Minimum norm estimation ... 37
2.2.5 Beamforming ... 38
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Uncovering brain networks: Functional connectivity ... 40
3.1 How neurons connect ... 40
3.2 Brain networks during tasks and at rest ... 40
3.2.1 Functional connectivity ... 40
3.2.2 Task-related functional connectivity ... 42
3.2.3 Resting-state functional connectivity ... 43
3.3 Modes of electrophysiological functional connectivity ... 46
3.3.1 Phase coupling measures ... 47
3.3.2 Amplitude coupling measures ... 50
3.3.3 Spatial source leakage ... 51
Preface to Chapter 4 ... 53
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Do the posterior midline cortices belong to the electrophysiological default-mode network? ... 56
4.1 Introduction ... 56
4.2 Methods ... 58
4.2.1 Data collection and preprocessing ... 58
4.2.2 Source reconstruction algorithms ... 59
4.2.3 Electrophysiological functional connectivity... 60
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4.3 Results ... 63
4.3.1 Empirical analysis of DMN connectivity at rest ... 63
4.3.2 Point-like PMC source with linear PMC-TPJ coupling ... 67
4.3.3 Spatially extended linear synchronization within the PMC ... 70
4.4 Discussion ... 72
4.4.1 The PMC is a part of the electrophysiological DMN ... 72
4.4.2 Linear synchronization structure at rest ... 73
4.4.3 A practical guideline for DMN resting-state studies ... 77
4.5 Supplementary methods and results ... 79
4.5.1 Robustness of empirical results against precise seed positioning ... 79
4.5.2 Robustness of empirical results against precise choice of DMN regions of interest ... 80
4.5.3 Impact of source-space grid resolution on the mPFC-PMC coupling estimate ... 81
4.5.4 Impact of one-dimensional source projection on connectivity estimation ... 82
4.5.5 Necessity of increased PMC variance in point-like PMC simulations ... 83
4.5.6 Establishing network-independent FC reduction with the LCMV beamformer ... 84
4.5.7 Necessity of bi-laterality for the linear PMC-TPJ coupling in point-like PMC simulations ... 85
Preface to Chapter 5: Task-modulation and clustering ... 87
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Intrinsic/extrinsic duality of large-scale neural functional integration in the human brain ... 94
5.1 Introduction ... 94
5.2 Methods and results ... 95
5.2.1 Network-level functional connectivity ... 95
5.2.2 Task-dependent states of amplitude correlation ... 97
5.2.3 Task-dependent states of phase coupling... 101
5.2.4 Amplitude correlation modulates phase coupling ... 103
5.2.5 Phase coupling exhibits intrinsic dynamics ... 104
5.3 Discussion ... 107
5.4 Expanded methods and supplementary results ... 111
5.4.1 Expanded methods ... 112
5.4.2 Supplementary results ... 127
Preface to Chapter 6: Multiple sclerosis and cognition ... 149
6
Brain dysconnectivity relates to disability and cognitive impairment in multiple sclerosis ... 157
6.1 Introduction ... 157
6.2 Methods ... 158
6.2.1 Participants ... 158
6.2.2 Neuropsychological and neurological evaluation ... 160
6.2.3 Data acquisition ... 160
6.2.4 MEG data preprocessing ... 161
6.2.5 Source reconstruction ... 162
6.2.6 Connectivity analysis ... 163
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6.2.8 Structural vs. functional modeling of CI... 168
6.3 Results ... 169
6.3.1 Comparison of clinical and neuropsychological scores ... 170
6.3.2 Comparison of rsFC ... 170
6.3.3 Correlation between rsFC and EDSS score in MS patients ... 172
6.3.4 Correlation between rsFC and disease duration in MS patients ... 173
6.3.5 Correlations between rsFC and verbal fluency ... 175
6.3.6 Correlations between rsFC and cognitive fatigue ... 177
6.4 Discussion ... 179
6.4.1 Reduced sensorimotor network functional connectivity related to motor disability ... 180
6.4.2 Network-level reduction of functional connectivity of the default-mode network ... 182
6.4.3 Disease duration is correlated with reduced language network functional connectivity ... 183
6.4.4 Reorganization of resting-state networks correlated with verbal fluency and cognitive fatigue ... 184
6.4.5 Methodological considerations and limitations ... 186
6.4.6 Conclusion ... 189
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Conclusions, perspectives and limitations ... 191
7.1 General conclusions and future perspectives ... 191
7.1.1 Dual task-related behaviors of intra-DMN phase synchronization ... 192
7.1.2 Is intrinsic FC broken or modulated by disease? ... 194
7.1.3 Intrinsic-extrinsic FC modulation ... 194
7.1.4 Time scales of intrinsic FC changes ... 195
7.2 General limitations ... 196
