Fig 1.
EEG acquisition and classification.
(A) The locations of the three carbon electrodes implanted subcutaneously on top of the skull for EEG acquisition. (B) Representative EEG signals with artifacts removed and spike and sharp-wave marked. Color-coded sub-types of spikes (C) and sharp-waves (D). In both subplots, the black lines in different styles represent the averaged temporal profiles for each sub-type. EEG = electroencephalography.
Table 1.
Frequency of Interictal Epileptiform Discharges (IEDs).
Fig 2.
IED-evoked BOLD activations and deactivations.
(A) A representative collection of a particular spike sub-type (10 events, Rat 6). The black dashed line represents the average of all events. (B) 3-D display of brain regions with either positive (red) or negative (blue) BOLD responses evoked by the spike sub-type shown in (A). In this case, the distance between the BOLD responses is 2.08 mm. (C) Hemodynamic response functions (HRFs) extracted from the regions with a positive and a negative BOLD responses shown in (B). (D) A representative collection of a particular sharp-wave sub-type (9 events, Rat 1). The black dashed line represents the average of all events. (E) 3-D display of the regions showing either a positive (red) or a negative BOLD response evoked by the spike sub-type shown in (D). The distances between the region with a negative BOLD response and those two with a positive BOLD response are 6.92 mm (right hemisphere) and 5.91 mm (left hemisphere). (F) HRFs extracted from the regions with either a positive or a negative BOLD response shown in (E). (G) Numbers of the positive (red) and the negative (blue) BOLD regions versus the IED sub-type. For example, among all the studied rats, there are thirteen sub-types of IEDs that induce BOLD activation in a single brain area. R = right; L = left; BOLD = blood-oxygen-level dependent; IED = interictal epileptiform discharge.
Table 2.
Frequency of Classified Genuine Interictal Epileptiform Discharges (IEDs).
Fig 3.
Distributions of irritative zones and morphological changes.
(A) Comparisons of the numbers of IED-evoked BOLD response clusters for five cortical regions. The numbers of clusters in the sensory areas were significantly larger than those in other cortical areas. (B) Comparisons of the volume reduction in the same five brain regions as depicted in (A). The dash line indicates zero-change. The volume reductions in sensory and other cortices in the parietal and the temporal regions were significant (p < 0.05). No significant differences were found among cortical regions. (C) Coronal T2-weighted images of Rat 2 (in yellow) overlapped with the averaged brain templates (in grey) after registration (illustrated in MRIcroGL). Clear reduction in the cortical thickness was found in the anterior commissure. All compared to sensory cortex. *: p<0.05. **: p<0.01. ***: p<0.001. No asterisk means no significant difference. IED = interictal epileptiform discharge; BOLD = blood-oxygen-level dependent.
Fig 4.
(A) Illustration of the causal relationship among BOLD response clusters evoked by all identified sub-types of genuine IEDs (n = 5) for Rat 2 (left). The actual locations and extensions for all BOLD response clusters are shown on the right (activations—red and deactivations—blue). The predominant relationship shown here was that BOLD deactivations have a directed influence on activations. (B) Summary of the Granger causality analysis for all six rats. The blue bars were from the results of the analysis including only clusters in the cortex. Most of these clusters showed no causal relationships (n = 22). The orange bars were from the analysis performed including clusters from both the cortical and subcortical regions. Both analyses depicted that predominantly areas with BOLD deactivations have directed influences on areas with activations. (C) Histogram of the distance between cortical areas with activation and deactivation. The mode of the distribution is 4.47 mm, marked by black solid line. (D) Histogram of the distance between activation and deactivation but, in this case, including areas from the entire brain, i.e. cortical and sub-cortical regions. The mode of the distribution is 5.52 mm, marked by the black solid line. R = right; L = left; BOLD = blood-oxygen-level dependent; IED = interictal epileptiform discharge.
Fig 5.
Example of the regional pairwise correlation coefficient (RPCC) map of the averaged resting-state time series in the cortical regions of Rat 2.
Numbers 1–48 represent cortical regions on the right hemisphere and numbers 49–96 represent cortical regions on the left hemisphere. The abbreviations of the cortical regions are defined by Paxions et al. [45]. Areas not covered by the echo planar imaging acquisitions are left blank. The color-bar represents the RPCC value; dark red indicates strong correlation (r>0.8) and deep blue strong anti-correlation (r<-0.8).
Table 3.
Summary of all Analysis.
Fig 6.
Independent component analysis (ICA)-based resting state networks.
A) Example of bilateral connectivity (Rat 4). B) Example of unilateral connectivity (Rat 2). C) Example of diffused connectivity (Rat 6). R = right; L = left.
Fig 7.
The blue cluster tree is obtained using the data in Table 3 as the input for hierarchical clustering. The height of the cluster tree is the cophenetic distance between two different classes in an arbitrary unit. The horizontal axis is the rat number. All the labels on the top of the blue lines represent descriptions of the common feature of the irritative zone distribution within each class. The 3-D BOLD response maps of the distribution of irritative zones obtained from these six rats are displayed below the cluster tree. R = right; L = left; BOLD = blood-oxygen-level dependent.
Fig 8.
Representative relationship between the IED-evoked BOLD responses and RSN from Rat 2.
(A) and (B) show two different axial and coronal slices with IED-evoked BOLD responses overlapped with RSN. RSN’s symmetry was disturbed in (A) due to the existence of two IED-evoked BOLD responses (black dash circles). Overlap between RSNs and IED-evoked BOLD responses exists preferentially on the left hemisphere. (B) Distant IED-evoked BOLD responses are connected by RSN (black arrow). IED = interictal epileptiform discharge; BOLD = blood-oxygen-level dependent; RSN = resting-state network; R = right; L = left; A = anterior; P = posterior.
Fig 9.
Two possible scenarios by means of which the resting-state network and the irritative zone network might be intrinsically related. A mechanistic explanation for the directed influences among elements from the irritative zone network are provided. NA = neuronal activity; BOLD = blood-oxygen-level dependent; IED = interictal epileptiform discharge; RSN = resting-state network.