Figure 1 Summary of patient-level SC-FC analysis pipeline

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Figure 1 Summary of patient-level SC-FC analysis pipeline Figure 1 Summary of patient-level SC-FC analysis pipeline. (A) HARDI preprocessing and whole-brain tractography was ... Figure 1 Summary of patient-level SC-FC analysis pipeline. (A) HARDI preprocessing and whole-brain tractography was carried out. (B) iEEG data were preprocessed and seizures were annotated, with each seizure event consisting of an ictal period and an associated pre-ictal period of equivalent duration. (C) Regions of interest (ROIs) were selected via a one-to-one spatial correspondence between electrode centroids and atlas regions. (D) The structural connectivity (SC) network was generated using log-normalized streamline counts between atlas regions of interest associated with each electrode location. (E) Time-varying broadband functional connectivity (FC) networks were generated for each 1 s time window by computing correlation between iEEG signals across electrode pairs. Frequency-specific functional connectivity networks were similarly computed using coherence between iEEG signals across electrode pairs. (F) SC-FC relationships were quantified across time, frequency, and space (see ‘Materials and methods’ section for details). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 2 SC-FC analysis using broadband functional connectivity Figure 2 SC-FC analysis using broadband functional connectivity. (A) Temporal dynamics of SC-FC correlation as ... Figure 2 SC-FC analysis using broadband functional connectivity. (A) Temporal dynamics of SC-FC correlation as measured by Fisher’s z for one example seizure in one patient, along with permutation-based null distribution of z values (mean ± standard deviation). (B) Per-seizure z-values during interictal, pre-ictal, and ictal periods reveal SC-FC correlations significantly greater than chance across all periods (P < 0.05). (C) Temporal dynamics of SC-FC correlation across all subjects (mean ± standard deviation across seizures in each subject). For visualization purposes only, time courses were normalized to span 200 evenly spaced time windows (100 pre-ictal and 100 ictal) and smoothed with a 5-window moving average filter. (D) Per-seizure paired differences in mean z-values reveal significantly greater SC-FC correlation during ictal periods than pre-ictal periods (P = 0.023). This effect holds when substituting pre-ictal periods with interictal periods (P = 0.021), with no significant difference between pre-ictal and interictal period SC-FC correlation values (P = 0.70). *P < 0.05. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 3 Frequency-specific SC-FC analysis Figure 3 Frequency-specific SC-FC analysis. (A) Temporal dynamics of SC-FC correlation as measured by Fisher’s z in ... Figure 3 Frequency-specific SC-FC analysis. (A) Temporal dynamics of SC-FC correlation as measured by Fisher’s z in α/θ, β, low-γ, and high-γ frequency bands (mean ± standard deviation across seizures in each subject, following interpolation to normalize ictal and pre-ictal durations). (B) Per-seizure z-values during interictal, pre-ictal, and ictal periods (mean ± SD) are significantly greater than chance (P < 0.05, permutation-based testing). (C) The increase in SC-FC correlation between pre-ictal and ictal periods is further illustrated using paired differences for each individual seizure (P < 0.05, linear mixed effects analysis with subject as random effect). (D) Seizures within subjects evolve similarly, as evidenced by higher between-patient Euclidean distances between SC-FC correlation time courses compared to within-patient distances (P < 0.001, R<sup>2 </sup>= 0.50, PERMANOVA). *P < 0.05. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 4 Assessment of SC-FC coupling in postictal periods Figure 4 Assessment of SC-FC coupling in postictal periods. (A) Illustration of broadband SC-FC coupling across ... Figure 4 Assessment of SC-FC coupling in postictal periods. (A) Illustration of broadband SC-FC coupling across pre-ictal, ictal, and postictal periods, in three example seizures. Each represents one of three observed distinct patterns of post-ictal SC-FC coupling: (top) SC-FC coupling persists, but does not increase, in the immediate postictal period and subsequently decreases, (middle) SC-FC coupling increases into the immediate postictal period and later decreases, and (bottom) SC-FC coupling decreases sharply at or prior to the start of the postical period. (B) Per-seizure paired differences in mean z-values reveal significant decreases in SC-FC coupling between ictal periods and later postictal (Minutes 1–5) periods across all tested frequency bands, with significant differences between SC-FC coupling between ictal periods and immediate postictal (Minutes 0–1) periods occurring only in α/θ and β frequency bands. (P < 0.05, linear mixed effects analysis with subject as random effect). Pre-ictal period bars included for reference. *P < 0.05. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 5 Assessment of SC-FC coupling in focal to bilateral tonic-clonic seizures. (A) Illustration of SC-FC coupling ... Figure 5 Assessment of SC-FC coupling in focal to bilateral tonic-clonic seizures. (A) Illustration of SC-FC coupling in two focal to bilateral tonic-clonic seizures, one from Subject 1 and one from Subject 3, reveals decrease in SC-FC coupling following bilateral tonic-clonic (BTC) onset (bilateral tonic-clonic onset indicated by dotted red line). For comparison, SC-FC coupling time course from a focal impaired awareness seizure in Subject 3 (without bilateral tonic-clonic) does not illustrate the same decrease. (B) In all bilateral tonic-clonic seizures, per-seizure paired differences in mean z-values reveal significantly greater SC-FC correlation during pre-bilateral tonic-clonic ictal periods than pre-ictal periods (P < 0.05), as well as significantly greater SC-FC correlation during pre-bilateral tonic-clonic ictal periods than post-bilateral tonic-clonic ictal periods (P < 0.05). *P < 0.05. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 6 Subject-specific virtual edge resection approach to determine the contribution, σ(i), of each structural edge ... Figure 6 Subject-specific virtual edge resection approach to determine the contribution, σ(i), of each structural edge i on the increase in SC-FC correlation during seizures. Results are shown for an example seizure in a patient with left temporal lobe epilepsy. Only ‘contributor’ edges [σ(i) > 0 and Δzictal(i)>0] are included to highlight edges that are associated with the SC-FC increase, with edge thickness and colour used to representing magnitude of σ(i). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 7 Relationship between edge contribution and edge length Figure 7 Relationship between edge contribution and edge length. Findings reveal that contributor edges are ... Figure 7 Relationship between edge contribution and edge length. Findings reveal that contributor edges are shorter-range in terms of both (A) Euclidean distance and (C) streamline length (P < 0.05, two-tailed paired t-test). Furthermore, there is a trend that edges with higher contribution are shorter-range, in terms of both (B) Euclidean distance and (D) streamline length, with significant differences between low and medium contribution edges (P < 0.05, two-tailed paired t-test), and low and high contribution edges (P < 0.05, two-tailed paired t-test). *P < 0.05. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz125, https://doi.org/10.1093/brain/awz125 The content of this slide may be subject to copyright: please see the slide notes for details.