Direct Cortical Stimulation to Probe the Ictogenicity of the Epileptogenic Nodes in Temporal Lobe Epilepsy.

Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns. Therefore, using direct cortical stimulation (DCS) as a probing tool to identify seizure generators, we systematically evaluated the causality of the high EI nodes (>0.3) in replicating the patient's habitual seizures. Specifically, we assessed the diagnostic yield of high EI nodes, i.e., the proportion of high EI nodes that evoked habitual seizures. A retrospective single-center study that included post-stereo encephalography (SEEG) confirmed TLE patients (n = 37) that had all high EI nodes stimulated, intending to induce a seizure. We evaluated the nodal responses (true and false responder rate) to stimulation and correlated with electrographic seizure onset patterns (hypersynchronous-HYP and low amplitude fast activity patterns-LAFA) and clinically defined SOZ. The ictogenicity (i.e., the propensity to induce the patient's habitual seizure) of a high EI node was only 44.5%. The LAFA onset pattern had a significantly higher response rate to DCS (i.e., higher evoked seizures). The concordance of an evoked habitual seizure with a clinically defined SOZ with good outcomes was over 50% (p = 0.0025). These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders) from hyperexcitable nodes that may be involved in early propagation.

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus.

OBJECTIVE: The goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability). METHODS: Five patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT. We analyzed the extent of gamma-band response (activation or suppression) and post-stimulation change in excitability in various cortical regions during low (10 Hz) and high (50 Hz) frequency stimulations. RESULTS: 10 Hz stimulation increased cortical gamma, whereas 50 Hz stimulation suppressed the gamma responses. The maximum response to stimuli was in the hippocampus. High epileptogenicity regions were more susceptible to stimulation. Both 10-and 50 Hz stimulations decreased post-stimulation cortical excitability. The greater the gamma-band activation with 10 Hz stimulation, the greater was the decrease in post-stimulation excitability. CONCLUSIONS: We define an EEG marker that delineates stimulation-specific nodal engagement. We proved that nodes that were engaged with the thalamus during stimulation were more likely to show a short term decrease in post-stimulation excitability. SIGNIFICANCE: Patient-specific engagement patterns during stimulation can be mapped with SEEG that can be used to optimize stimulation parameters.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

OBJECTIVE: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). METHODS: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. RESULTS: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. CONCLUSIONS: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Spectral organization of focal seizures within the thalamotemporal network.

OBJECTIVE: To investigate dynamic changes in neural activity between the anterior nucleus of the thalamus (ANT) and the seizure onset zone (SOZ) in patients with drug-resistant temporal lobe epilepsy (TLE) based on anatomic location, seizure subtype, and state of vigilance (SOV). METHODS: Eleven patients undergoing stereoelectroencephalography for seizure localization were recruited prospectively for local field potential (LFP) recording directly from the ANT. The SOZ was identified using line length and epileptogenicity index. Changes in power spectral density (PSD) were compared between the two anatomic sites as seizures (N = 53) transitioned from interictal baseline to the posttermination stage. RESULTS: At baseline, the thalamic LFPs were significantly lower and distinct from the SOZ with the presence of higher power in the fast ripple band (P < 0.001). Temporal changes in ictal power of neural activity within ANT mimic those of the SOZ, are increased significantly at seizure onset (P < 0.05), and are distinct for seizures that impaired awareness or that secondarily generalized (P < 0.05). The onset of seizure was preceded by a decrease in the mean power spectral density (PSD) in ANT and SOZ (P < 0.05). Neural activity correlated with different states of vigilance at seizure onset within the ANT but not in the SOZ (P = 0.005). INTERPRETATION: The ANT can be recruited at the onset of mesial temporal lobe seizures, and the recruitment pattern differs with seizure subtypes. Furthermore, changes in neural dynamics precede seizure onset and are widespread to involve temporo-thalamic regions, thereby providing an opportunity to intervene early with closed-loop DBS.

Auras localized to the temporal lobe disrupt verbal memory and learning - Causal evidence from direct electrical stimulation of the hippocampus.

Auras (focal aware seizure; FAS) are subjective ictal events with retained consciousness. Epileptiform activities can disrupt cognitive tasks, but studies are limited to seizures with impaired awareness. As a proof of concept, we examined the cognitive effects of direct electrical stimulation to the left hippocampus which induced a habitual FAS in a patient with left mesial temporal lobe epilepsy. During the induced habitual FAS, verbal memory performance declined significantly as compared to pre-stimulation testing. Tasks measuring auditory working memory and psychomotor processing speed were not affected by the stimulation. The study confirms that FAS can impair episodic verbal memory and learning.

Conceptual and Biofunctional Embodiment: A Long Story on the Transience of the Enduring Mind.

We examine how embodiment in biological activity is different from conceptual embodiment as reflected in classic, modern, and postmodern perspectives on tacit knowledge. The central theme of the essay is how understanding is embodied conceptually and biofunctionally. We focus (a) on how biofunctional understanding (BU) is different from conceptual understanding (CU) and (b) on how the overall differences between these two types of embodied understanding are complementary. We show here from a conceptual perspective that embodiment theories have diverged on the meaning of embodiment; but convergence may be more likely across future perspectives if we first redefine the construct of tacit knowledge as tacit understanding and then define (explicit) CU as being directly grounded in tacit understanding, for the purpose of comparison with BU defined as being grounded in biological activity. We illustrate the complementary differences between conceptual and biofunctional embodiment of understanding first in the absence of language and then using a particular statement format and the implicit analogy of biofunctional embodiment in other bodily systems. We conclude with a suggestion about the directly uncovered but highly related embodiment of language in a section on future research.