Effective connectivity differs between focal cortical dysplasia types I and II.

OBJECTIVE: To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II. METHODS: We compared cortico-cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug-resistant focal epilepsy who underwent intracranial evaluation with stereo-electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal-onset single-pulse electrical stimulation (iSPES). RESULTS: In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal-onset zone (<50 mm). These findings persisted when controlling for the location of the epileptogenic zone, as noted in patients with temporal lobe epilepsies, as well as controlling for seizure type, as noted in patients with focal to bilateral tonic-clonic seizures (FBTCS). In type II, the root mean square (RMS) of CCEP responses dropped substantially from the early segment (10-60 ms) to the middle and late segments (60-600 ms). The middle and late CCEP latency segments showed the largest differences between FCD types I and II. SIGNIFICANCE: Focal cortical dysplasia type I may have a greater degree of cortical hyperexcitability as compared with FCD type II. In addition, FCD type II displays a more restrictive area of hyperexcitability in both temporal and spatial domains. In patients with FBTCS and type I FCD, the increased amplitudes of RMS in the middle and late CCEP periods appear consistent with the cortico-thalamo-cortical network involvement of FBTCS. The notable differences in degree and extent of hyperexcitability may contribute to the different postsurgical seizure outcomes noted between these two pathological substrates.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Multilayer brain networks can identify the epileptogenic zone and seizure dynamics.

Seizure generation, propagation, and termination occur through spatiotemporal brain networks. In this paper, we demonstrate the significance of large-scale brain interactions in high-frequency (80-200Hz) for the identification of the epileptogenic zone (EZ) and seizure evolution. To incorporate the continuity of neural dynamics, here we have modeled brain connectivity constructed from stereoelectroencephalography (SEEG) data during seizures using multilayer networks. After introducing a new measure of brain connectivity for temporal networks, named multilayer eigenvector centrality (mlEVC), we applied a consensus hierarchical clustering on the developed model to identify the EZ as a cluster of nodes with distinctive brain connectivity in the ictal period. Our algorithm could successfully predict electrodes inside the resected volume as EZ for 88% of participants, who all were seizure-free for at least 12 months after surgery. Our findings illustrated significant and unique desynchronization between EZ and the rest of the brain in the early to mid-seizure. We showed that aging and the duration of epilepsy intensify this desynchronization, which can be the outcome of abnormal neuroplasticity. Additionally, we illustrated that seizures evolve with various network topologies, confirming the existence of different epileptogenic networks in each patient. Our findings suggest not only the importance of early intervention in epilepsy but possible factors that correlate with disease severity. Moreover, by analyzing the propagation patterns of different seizures, we demonstrate the necessity of collecting sufficient data for identifying epileptogenic networks.

Electrophysiological scarring in remitted depressed patients: Elevated EEG functional connectivity between the posterior cingulate cortex and the subgenual prefrontal cortex as a neural marker for rumination.

INTRODUCTION: Prior resting state fMRI studies have revealed that elevated connectivity between the default mode network (DMN) and subgenual prefrontal cortex (sgPFC) connectivity may underly maladaptive rumination, which is a major risk factor for depression. To further evaluate such relationship, we investigated whether posterior regions of the DMN, showed elevated connectivity with the sgPFC in remitted depressed patients (rMDD) and whether this connectivity was related to maladaptive rumination. METHODS: We examined whether rMDD (N = 20) had elevated EEG posterior DMN - sgPFC functional connectivity when compared to age and sex matched healthy controls (N = 17), and whether this posterior DMN - sgPFC connectivity positively correlated with rumination. Using minimum norm as the source estimation method, we extracted current density maps from six regions of interest (ROIs) within the posterior DMN. EEG source-space functional connectivity was calculated using the Amplitude Envelope Correlation method. RESULTS: Relative to controls, rMDD showed increased posterior cingulate cortex (PCC) - sgPFC connectivity in the beta-3 (25-30 Hz) band. As hypothesized, PCC - sgPFC connectivity was positively associated with rumination for rMDD, even after controlling for depression and anxiety. LIMITATIONS: The absence of an MDD patient group and the relatively small sample size can limit the generalizability of the results. CONCLUSIONS: EEG resting state PCC - sgPFC functional connectivity is significantly elevated in rMDD and is associated with rumination, suggesting that EEG PCC - sgPFC connectivity may be useful as a neural marker to identify individuals at risk for depression.