Fig 1.
Stereotactic Electroencephalographic (SEEG) data of patient CJ.
Left panel: time series of partial seizures recorded with SEEG. The colored bars indicate the EZ (red)and PZ (blue). Right panel: On the top, the spatial organization of the EZ and PZ is shown on the left hemisphere, frontal-lateral and lateral view. Below, spatiotemporal activation patterns are plotted at different time points of the seizures. The same time points highlighted with black dashed lines in the left panel. lh-SPC, left superior parietal cortex; lh-IPC, left inferior parietal cortex; lh-LgG, left lingual gyrus; lh-LOC, left lateral occipital cortex; lh-FuG, left fusiform gyrus; lh-PC, left Pericalcarine; lh-ITG, left inferior temporal gyrus.
Fig 2.
Scheme for comparison of standard resection methods, where the entire epileptogenic zone (EZ) is removed during surgical operation, versus lesioning minimal number of links.
Panel (a): The connectivity matrix is illustrated for an epileptogenic brain with the EZ consisting of one area (black). The outgoing connections of the EZ are blue and pink, connecting red and dark grey areas respectively, and they are all removed during the current surgical procedures of disconnecting the EZ. Targeted lesioning depicts the minimal number of links that are sufficient to be removed (pink) in order to stop the seizure, versus the total number of outgoing links from the EZs (blue) that are removed during the resection of an entire EZ. Light blue links added in panel (b) represent the full connectivity of the network. The size of the nodes reflects how strongly they are connected, and the width of the links correspond to their weight. Unaffected nodes by any of the resection procedures are light grey and unaffected links are light blue.
Fig 3.
Comparison between the results obtained with 5 different lesioning procedures for each of the 15 analyzed patients.
In particular it is shown the numbers of links that are cut in order to stop the seizure propagation, if i) the entire EZ is removed (black dots); ii) random cuts are done (red diamonds); iii) the strongest links outgoing the macroarea (EZ + PZ) are removed; iv) the strongest links outgoing the EZ are cut; v) selected lesions are done following Linear Stability Analysis indications (green stars). The data for the case (ii) are calculated averaging over 5 different realizations of random lesioning procedures. Patients are ordered according to the extension of their EZ: the focus is represented as a single node for patients cj-pg; 2 nodes for patients ac-ml; 3 nodes for patients cv and fbo; 4 nodes for patients jc-sf; 6 nodes for rb.
Fig 4.
Clinical history: occipital epilepsy type (left size). EZ region: Lateral occipital cortex. PZ prediction: Fusiform gyrus, Superior parietal cortex, Inferior temporal gyrus, Inferior parietal cortex, Pericalcarine, Lingual gyrus. PZ clinical prediction: Inferior parietal cortex, Superior parietal cortex. Lesions: links between regions LOC-FuG, LOC-SPC, LOC-ITG, LOC-IPC, LOC-PC, LOC-LgG must be cut in order to stop the seizure (lesions are performed in correspondence of the time identified by the dashed blue line). Upper panels: Time series generated by the implemented brain network model with the connectome of patient CJ. On the left the PZ (blue curves) is recruited immediately after the seizure (red curve) is emitted; on the right the recruitment is no more possible after the targeted disconnection is performed. Lower panel: Seizure events as a function of time. The connectivity matrix consists of 88 nodes and the EZ corresponds to 21. Seizures emitted by node 21 are highlighted in red, while the others are given in black. Green dashed line corresponds to the time at which lesions occur. The blue ellipse highlights the moment in time at which the PZ is recruited after the seizure emitted by the EZ.
Fig 5.
Panel (a): Eigenvalues of the system when the original structural connectivity is considered as a network structure (black circles). The index i on the x-axis represents the eigenvalues index (for more details see SI). Red squares represent the eigenvalues of the networks when the link between the populations (nodes) LOC-FuG (21-17) is removed. Green diamonds represent the eigenvalues of the networks when the links between the populations (nodes) LOC-FuG, LOC-SPC (21-17, 21-39) are removed. Blue triangles represent the eigenvalues of the networks when 3 connections between the regions (nodes) LOC-FuG, LOC-SPC, LOC-ITG (21-17, 21-39, 21-19) are removed. Orange triangles represent the activity when 4 connections between the regions (nodes) LOC-FuG, LOC-SPC, LOC-ITG, LOC-IPC (21-17, 21-39, 21-19, 21-18) are removed. Magenta stars: links between the regions (nodes) LOC-FuG, LOC-SPC, LOC-ITG, LOC-IPC, LOC-PC (21-17, 21-39, 21-19, 21-18, 21-31) are removed. Turquoise triangles: links between the populations (nodes) LOC-FuG, LOC-SPC, LOC-ITG, LOC-IPC, LOC-PC, LOC-LgG (21-17, 21-39, 21-19, 21-18, 21-31, 21-23) are removed. In the inset is shown an enlargement of the first, positive part of the spectra. Panel (b): Maximal eigenvectors calculated when the original structural matrix is considered as network structure and when successive links are removed. Symbols and the color code are the same as in panel (a). The blue lines represent the most unstable localized nodes to which are associated the most unstable directions. In particular panel (b1) shows the situation where the structural matrix is intact (black circles) and where the first link has been removed (red squares). Removing the link between the populations (nodes) LOC-FuG (21-17) corresponds to the loss of importance of node 17, which is not localized anymore. In panel (b2) are shown the maximal eigenvectors in case 2 removals (green diamonds), 3 removals (blue triangles) and 4 removals (orange triangles) are operated. Every time an additional link is cut according to the Linear Stability Analysis procedure detailed for panel (a), the corresponding node does not appear any more as important (i. e. localized) when calculating the maximal eigenvector. Finally in panel (b3) are shown the maximal eigenvectors in case 5 removals (magenta stars) and 6 removals (turquoise triangles) are operated: when all the relevant lesions are performed there are no more localized nodes (except the EZ), thus suggesting that the unstable directions are not accessible anymore.
Fig 6.
Panel (a): Number of lesions necessary to stop seizure propagation as a function of the epileptogenic region. Panel (b): Dependence of the PZ size on each lesion, as a function of the EZ. The color code indicates the number of regions belonging to the PZ, from 0 (white pixel) to 17 (red pixel).
Fig 7.
Number of lesions needed to stop the propagation for different graph measures of each EZ, calculated for the connectivity matrix of the patient CJ.
Graph metrics reported on the x-axis are: (a) efficiency; (b) strength; (c) clustering; (d) degree; (e) betweenness; (f) centrality. The red line in each panel shows the correlation among the data, and the estimated Pearson correlation coefficient is: (a) 0.8615377; (b) 0.6735522; (c) 0.765353; (d) 0.540695; (e) 0.7852488; (f) 0.7165724. All p values of statistical significance are below 10−6.
Table 1.
Comparison of the minimum necessary number of lesions for stopping the seizure propagation for different lesioning procedures.