Psychiatric complications following SEEG-guided radiofrequency thermocoagulations in patients with drug-resistant epilepsy.

SEEG-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic regions is a therapeutic option for patients with drug-resistant focal epilepsy who may have or not indication for epilepsy surgery. The most common adverse events of RF-TC are seizures, headaches, somatic pain, and sensory-motor deficits. If RF-TC could lead to psychiatric complications is unknown. In the present study, seven out of 164 patients (4.2 %) experienced psychiatric decompensation with or without memory deterioration after RF-TC of bilateral or unilateral amygdala and hippocampus. The appearance of symptoms was either acute, subacute, or chronic and the symptoms were either transient or lasted for several months. Common features among these patients were female sex, mesial temporal epilepsy, and a pre-existing history of psychological distress and memory dysfunction. Our study highlights the possibility of neuropsychiatric deterioration in specific patients following SEEG-guided RF-TC, despite its rarity.

Right-sided vagus nerve stimulation for drug-resistant epilepsy: A systematic review of the literature and perspectives.

BACKGROUND: Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side. OBJECTIVE: The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety. METHODS: A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy. RESULTS: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively). CONCLUSION: Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients.

Modification of brain conductivity in human focal epilepsy: A model-based estimation from stereoelectroencephalography.

OBJECTIVE: We have developed a novel method for estimating brain tissue electrical conductivity using low-intensity pulse stereoelectroencephalography (SEEG) stimulation coupled with biophysical modeling. We evaluated the hypothesis that brain conductivity is correlated with the degree of epileptogenicity in patients with drug-resistant focal epilepsy. METHODS: We used bipolar low-intensity biphasic pulse stimulation (.2 mA) followed by a postprocessing pipeline for estimating brain conductivity. This processing is based on biophysical modeling of the electrical potential induced in brain tissue between the stimulated contacts in response to pulse stimulation. We estimated the degree of epileptogenicity using a semi-automatic method quantifying the dynamic of fast discharge at seizure onset: the epileptogenicity index (EI). We also investigated how the location of stimulation within specific anatomical brain regions or within lesional tissue impacts brain conductivity. RESULTS: We performed 1034 stimulations of 511 bipolar channels in 16 patients. We found that brain conductivity was lower in the epileptogenic zone (EZ; unpaired median difference = .064, p < .001) and inversely correlated with the epileptogenic index value (p < .001, Spearman rho = -.32). Conductivity values were also influenced by anatomical site, location within lesion, and delay between SEEG electrode implantation and stimulation, and had significant interpatient variability. Mixed model multivariate analysis showed that conductivity is significantly associated with EI (F = 13.45, p < .001), anatomical regions (F = 5.586, p < .001), delay since implantation (F = 14.71, p = .003), and age at SEEG (F = 6.591, p = .027), but not with the type of lesion (F = .372, p = .773) or the delay since last seizure (F = 1.592, p = .235). SIGNIFICANCE: We provide a novel model-based method for estimating brain conductivity from SEEG low-intensity pulse stimulations. The brain tissue conductivity is lower in EZ as compared to non-EZ. Conductivity also varies significantly across anatomical brain regions. Involved pathophysiological processes may include changes in the extracellular space (especially volume or tortuosity) in epileptic tissue.

Stereo-EEG-based ictal functional connectivity in patients with periventricular nodular heterotopia-related epilepsy.

Nodular heterotopia (NH)-related drug-resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo-electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH-related drug-resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT-strength than the channels within the gray matter (p = .03), with higher node OUT-strength than node IN-strength (p = .03). These results are in favor of a "leading" role of NH during seizure onset when involved in the epileptogenic- or propagation-zone network (50% of patients). However, when looking at the individual level, no significant difference between NH and gray matter was found, except for one patient (in two of three seizures). This result confirms the heterogeneity and the complexity of the epileptogenic network organization in NH and the need for SEEG exploration to characterize more precisely patient-specific epileptogenic network organization.

Permutation entropy-derived parameters to estimate the epileptogenic zone network.

OBJECTIVE: Quantification of the epileptogenic zone network (EZN) most frequently implies analysis of seizure onset. However, important information can also be obtained from the postictal period, characterized by prominent changes in the EZN. We used permutation entropy (PE), a measure of signal complexity, to analyze the peri-ictal stereoelectroencephalography (SEEG) signal changes with emphasis on the postictal state. We sought to determine the best PE-derived parameter (PEDP) for identifying the EZN. METHODS: Several PEDPs were computed retrospectively on SEEG-recorded seizures of 86 patients operated on for drug-resistant epilepsy: mean baseline preictal entropy, minimum ictal entropy, maximum postictal entropy, the ratio between the maximum postictal and the minimum ictal entropy, and the ratio between the maximum postictal and the baseline preictal entropy. The performance of each biomarker was assessed by comparing the identified epileptogenic contacts or brain regions against the EZN defined by clinical analysis incorporating the Epileptogenicity Index and the connectivity epileptogenicity index methods (EZNc), using the receiver-operating characteristic and precision-recall. RESULTS: The ratio between the maximum postictal and the minimum ictal entropy (defined as the Permutation Entropy Index [PEI]) proved to be the best-performing PEDP to identify the EZNC . It demonstrated the highest area under the curve (AUC) and F1 score at the contact level (AUC 0.72; F1 0.39) and at the region level (AUC 0.78; F1 0.47). PEI values gradually decreased between the EZN, the propagation network, and the non-involved regions. PEI showed higher performance in patients with slow seizure-onset patterns than in those with fast seizure-onset patterns. The percentage of resected epileptogenic regions defined by PEI was significantly correlated with surgical outcome. SIGNIFICANCE: PEI is a promising tool to improve the delineation of the EZN. PEI combines ease and robustness in a routine clinical setting with high sensitivity for seizures without fast activity at seizure onset.

3D and Multimodal X-Ray Microscopy Reveals the Impact of Voids in CIGS Solar Cells.

Small voids in the absorber layer of thin-film solar cells are generally suspected to impair photovoltaic performance. They have been studied on Cu(In,Ga)Se2 cells with conventional laboratory techniques, albeit limited to surface characterization and often affected by sample-preparation artifacts. Here, synchrotron imaging is performed on a fully operational as-deposited solar cell containing a few tens of voids. By measuring operando current and X-ray excited optical luminescence, the local electrical and optical performance in the proximity of the voids are estimated, and via ptychographic tomography, the depth in the absorber of the voids is quantified. Besides, the complex network of material-deficit structures between the absorber and the top electrode is highlighted. Despite certain local impairments, the massive presence of voids in the absorber suggests they only have a limited detrimental impact on performance.

Correspondence between scalp-EEG and stereoelectroencephalography seizure-onset patterns in patients with MRI-negative drug-resistant focal epilepsy.

OBJECTIVE: Our objective was to evaluate the relationship between scalp-EEG and stereoelectroencephalography (SEEG) seizure-onset patterns (SOP) in patients with MRI-negative drug-resistant focal epilepsy. METHODS: We analyzed retrospectively 41 patients without visible lesion on brain MRI who underwent video-EEG followed by SEEG. We defined five types of SOPs on scalp-EEG and eight types on SEEG. We examined how various clinical variables affected scalp-EEG SOPs. RESULTS: The most prevalent scalp SOPs were rhythmic sinusoidal activity (56.8%), repetitive epileptiform discharges (22.7%), and paroxysmal fast activity (15.9%). The presence of paroxysmal fast activity on scalp-EEG was always seen without delay from clinical onset and correlated with the presence of low-voltage fast activity in SEEG (sensitivity = 22.6%, specificity = 100%). The main factor explaining the discrepancy between the scalp and SEEG SOPs was the delay between clinical and scalp-EEG onset. There was a correlation between the scalp and SEEG SOPs when the scalp onset was simultaneous with the clinical onset (p = 0.026). A significant delay between clinical and scalp discharge onset was observed in 25% of patients and featured always with a rhythmic sinusoidal activity on scalp, corresponding to similar morphology of the discharge on SEEG. The presence of repetitive epileptiform discharges on scalp was associated with an underlying focal cortical dysplasia (sensitivity = 30%, specificity = 90%). There was no significant association between the scalp SOP and the epileptogenic zone location (deep or superficial), or surgical outcome. SIGNIFICANCE: In patients with MRI-negative focal epilepsy, scalp SOP could suggest the SEEG SOP and some etiology (focal cortical dysplasia) but has no correlation with surgical prognosis. Scalp SOP correlates with the SEEG SOP in cases of simultaneous EEG and clinical onset; otherwise, scalp SOP reflects the propagation of the SEEG discharge. PLAIN LANGUAGE SUMMARY: We looked at the correspondence between the electrical activity recorded during the start of focal seizure using scalp and intracerebral electrodes in patients with no visible lesion on MRI. If there is a fast activity on scalp, it reflects similar activity inside the brain. We found a good correspondence between scalp and intracerebral electrical activity for cases without significant delay between clinical and scalp electrical onset (seen in 75% of the cases we studied). Visualizing repetitive epileptic activity on scalp could suggest a particular cause of the epilepsy: a subtype of brain malformation called focal cortical dysplasia.

Controlled Li Alloying by Postsynthesis Electrochemical Treatment of Cu2ZnSn(S, Se)4 Absorbers for Solar Cells.

Li-alloying of Cu2ZnSn(S, Se)4 (CZTSSe) absorbers is widely accepted for its beneficial influence on the performance of CZTSSe-based thin film solar cells. Given the degraded morphology characteristic of absorbers synthesized in the presence of excess Li concentrations, it is speculated that Li may be best incorporated into the absorber after synthesis. Here, we report an innovative method to add Li to synthesized CZTSSe by an electrochemical treatment using a liquid electrolyte. Our approach decouples Li addition from absorber synthesis, allowing one to possibly overcome morphology issues associated with high Li concentration. We show that Li is thereby transferred to the absorber and is incorporated into the crystal lattice. The resulting Li concentration in the absorber can be easily controlled by the treatment parameters. Using liquid electrolytes allows a straightforward disassembly of the lithiation setup and hence the fabrication of solar cells after electrochemical treatment. Electrochemically lithiated solar cells reached power conversion efficiencies of up to 9.0%. Further optimization of this innovative method is required to reduce expected interface issues resulting from the electrochemical treatment to demonstrate a gain in the power conversion efficiency of the CZTSSe solar cells. Finally, our results indicate strong lateral Li diffusion, which deserves further investigation. Moreover, the method could be transferred to other material systems, such as Cu(In, Ga)Se2 (CIGS), and adapted to treat layers with other alkali elements such as Na.

Complications of Intracranial Multimodal Monitoring for Neurocritical Care: A Systematic Review and Meta-Analysis.

Intracranial multimodal monitoring (iMMM) is increasingly used for neurocritical care. However, concerns arise regarding iMMM invasiveness considering limited evidence in its clinical significance and safety profile. We conducted a synthesis of evidence regarding complications associated with iMMM to delineate its safety profile. We performed a systematic review and meta-analysis (PROSPERO Registration Number: CRD42021225951) according to the Preferred Reporting Items for Systematic Review and Meta-Analysis and Peer Review of Electronic Search Strategies guidelines to retrieve evidence from studies reporting iMMM use in humans that mention related complications. We assessed risk of bias using the Newcastle-Ottawa Scale and funnel plots. The primary outcomes were iMMM complications. The secondary outcomes were putative risk factors. Of the 366 screened articles, 60 met the initial criteria and were further assessed by full-text reading. We included 22 studies involving 1206 patients and 1434 iMMM placements. Most investigators used a bolt system (85.9%) and a three-lumen device (68.8%), mainly inserting iMMM into the most injured hemisphere (77.9%). A total of 54 postoperative intracranial hemorrhages (pooled rate of 4%; 95% confidence interval [CI] 0-10%; I2 86%, p < 0.01 [random-effects model]) was reported, along with 46 misplacements (pooled rate of 6%; 95% CI 1-12%; I2 78%, p < 0.01) and 16 central nervous system infections (pooled rate of 0.43%; 95% CI 0-2%; I2 64%, p < 0.01). We found 6 system breakings, 18 intracranial bone fragments, and 5 cases of pneumocephalus. Currently, iMMM systems present a similar safety profile as intracranial devices commonly used in neurocritical care. Long-term outcomes of prospective studies will complete the benefit-risk assessment of iMMM in neurocritical care. Consensus-based reporting guidelines on iMMM use are needed to bolster future collaborative efforts.

Human thalamic low-frequency oscillations correlate with expected value and outcomes during reinforcement learning.

Reinforcement-based adaptive decision-making is believed to recruit fronto-striatal circuits. A critical node of the fronto-striatal circuit is the thalamus. However, direct evidence of its involvement in human reinforcement learning is lacking. We address this gap by analyzing intra-thalamic electrophysiological recordings from eight participants while they performed a reinforcement learning task. We found that in both the anterior thalamus (ATN) and dorsomedial thalamus (DMTN), low frequency oscillations (LFO, 4-12 Hz) correlated positively with expected value estimated from computational modeling during reward-based learning (after outcome delivery) or punishment-based learning (during the choice process). Furthermore, LFO recorded from ATN/DMTN were also negatively correlated with outcomes so that both components of reward prediction errors were signaled in the human thalamus. The observed differences in the prediction signals between rewarding and punishing conditions shed light on the neural mechanisms underlying action inhibition in punishment avoidance learning. Our results provide insight into the role of thalamus in reinforcement-based decision-making in humans.

Non-invasive temporal interference electrical stimulation of the human hippocampus.

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders. However, its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modeling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging and behavioral experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.

The role of quantitative markers in surgical prognostication after stereoelectroencephalography.

OBJECTIVE: Stereoelectroencephalography (SEEG) is the reference method in the presurgical exploration of drug-resistant focal epilepsy. However, prognosticating surgery on an individual level is difficult. A quantified estimation of the most epileptogenic regions by searching for relevant biomarkers can be proposed for this purpose. We investigated the performances of ictal (Epileptogenicity Index, EI; Connectivity EI, cEI), interictal (spikes, high-frequency oscillations, HFO [80-300 Hz]; Spikes × HFO), and combined (Spikes × EI; Spikes × cEI) biomarkers in predicting surgical outcome and searched for prognostic factors based on SEEG-signal quantification. METHODS: Fifty-three patients operated on following SEEG were included. We compared, using precision-recall, the epileptogenic zone quantified using different biomarkers (EZq ) against the visual analysis (EZC ). Correlations between the EZ resection rates or the EZ extent and surgical prognosis were analyzed. RESULTS: EI and Spikes × EI showed the best precision against EZc (0.74; 0.70), followed by Spikes × cEI and cEI, whereas interictal markers showed lower precision. The EZ resection rates were greater in seizure-free than in non-seizure-free patients for the EZ defined by ictal biomarkers and were correlated with the outcome for EI and Spikes × EI. No such correlation was found for interictal markers. The extent of the quantified EZ did not correlate with the prognosis. INTERPRETATION: Ictal or combined ictal-interictal markers overperformed the interictal markers both for detecting the EZ and predicting seizure freedom. Combining ictal and interictal epileptogenicity markers improves detection accuracy. Resection rates of the quantified EZ using ictal markers were the only statistically significant determinants for surgical prognosis.

Ictal Fear during parietal seizures.

Ictal fear is characterized by subjective fear sensation and consistent clinical manifestations during seizures. This phenomenon is rarely observed in parietal seizures. We report anatomical electroclinical correlations of an SEEG-recorded seizure with prominent fear semiology. Seizure onset zone was quantified using the Connectivity Epileptogenicity Index method (cEI). Occurrence of fear during seizures was related to the involvement of the left inferior parietal cortex and the superior temporal gyrus without amygdala involvement. Our case confirms that parietal seizure can produce ictal fear without concomitant involvement of the limbic temporal network.

The origin of pleasant sensations: Insight from direct electrical brain stimulation.

Research into the neuroanatomical basis of emotions has resulted in a plethora of studies over the last twenty years. However, studies about positive emotions and pleasant sensations remain rare and their anatomical-functional bases are less understood than that of negative emotions. Pleasant sensations can be evoked by electrical brain stimulations (EBS) during stereotactic electroencephalography (SEEG) performed for pre-surgical exploration in patients with drug-resistant epilepsy. We conducted a retrospective analysis of 10 106 EBS performed in 329 patients implanted with SEEG in our epileptology department. We found that 13 EBS in 9 different patients evoked pleasant sensations (.60% of all responses). By contrast we collected 111 emotional responses of negative valence (i.e., 5.13% of all responses). EBS evoking pleasant sensations were applied at 50 Hz with an average intensity of 1.4 ± .55 mA (range .5-2 mA). Pleasant sensations were reported by nine patients of which three patients presented responses to several EBS. We found a male predominance among the patients reporting pleasant sensations and a prominent role of the right cerebral hemisphere. Results show the preponderant role of the dorsal anterior insula and amygdala in the occurrence of pleasant sensations.

Dimensionality and Ramping: Signatures of Sentence Integration in the Dynamics of Brains and Deep Language Models.

A sentence is more than the sum of its words: its meaning depends on how they combine with one another. The brain mechanisms underlying such semantic composition remain poorly understood. To shed light on the neural vector code underlying semantic composition, we introduce two hypotheses: (1) the intrinsic dimensionality of the space of neural representations should increase as a sentence unfolds, paralleling the growing complexity of its semantic representation; and (2) this progressive integration should be reflected in ramping and sentence-final signals. To test these predictions, we designed a dataset of closely matched normal and jabberwocky sentences (composed of meaningless pseudo words) and displayed them to deep language models and to 11 human participants (5 men and 6 women) monitored with simultaneous MEG and intracranial EEG. In both deep language models and electrophysiological data, we found that representational dimensionality was higher for meaningful sentences than jabberwocky. Furthermore, multivariate decoding of normal versus jabberwocky confirmed three dynamic patterns: (1) a phasic pattern following each word, peaking in temporal and parietal areas; (2) a ramping pattern, characteristic of bilateral inferior and middle frontal gyri; and (3) a sentence-final pattern in left superior frontal gyrus and right orbitofrontal cortex. These results provide a first glimpse into the neural geometry of semantic integration and constrain the search for a neural code of linguistic composition.SIGNIFICANCE STATEMENT Starting from general linguistic concepts, we make two sets of predictions in neural signals evoked by reading multiword sentences. First, the intrinsic dimensionality of the representation should grow with additional meaningful words. Second, the neural dynamics should exhibit signatures of encoding, maintaining, and resolving semantic composition. We successfully validated these hypotheses in deep neural language models, artificial neural networks trained on text and performing very well on many natural language processing tasks. Then, using a unique combination of MEG and intracranial electrodes, we recorded high-resolution brain data from human participants while they read a controlled set of sentences. Time-resolved dimensionality analysis showed increasing dimensionality with meaning, and multivariate decoding allowed us to isolate the three dynamical patterns we had hypothesized.

The anterior and pulvinar thalamic nuclei interactions in mesial temporal lobe seizure networks.

OBJECTIVE: To evaluate the respective roles of the anterior thalamic nucleus (ANT) and the medial pulvinar (PuM) during mesial temporal lobe seizures recorded by stereoelectroencephalography (SEEG). METHODS: We assessed functional connectivity (FC) in 15 SEEG recorded seizures from 6 patients using a non-linear correlation method. Functional interactions were explored between the mesial temporal region, the temporal neocortex, ANT and PuM. The node total-strength (the summed connectivity of the node with all other nodes) as well as the directionality of the links (IN and OUT strengths) were calculated to estimate drivers and receivers during the cortico-thalamic interactions. RESULTS: Significant increased thalamo-cortical FC during seizures was observed, with the node total-strength reaching a maximum at seizure end. There was no significant difference in global connectivity values between ANT and PuM. Regarding directionality, significantly higher thalamic IN strength values were observed. However, compared to ANT, PuM appeared to be the driver at the end of seizures with synchronous termination. CONCLUSIONS: This work demonstrates that during temporal seizures, both thalamic nuclei are highly connected with the mesial temporal region and that PuM could play a role in seizure termination. SIGNIFICANCE: Understanding functional connectivity between the mesial temporal and thalamic nuclei could contribute to the development of target-specific deep brain stimulation strategies for drug-resistant epilepsy.

"Plok-plok" syndrome: Posttraumatic stress disorder following an SEEG thermocoagulation and direct electrical stimulation procedure.

The psychological impact of intracerebral electroencephalography (stereoelectroencephalography [SEEG]) including the thermocoagulation procedure has not yet been clearly studied. We present a case of a patient who, following an SEEG procedure for presurgical evaluation of intractable focal epilepsy, developed severe symptoms of posttraumatic stress disorder. Such an occurrence may be under-estimated. Perceived traumatic exposure during SEEG and the development of posttraumatic psychological symptoms should be further studied in order to define risk factors and to improve the monitoring and psychological management of patients during their hospitalization. A careful and systematic procedure of prevention and support before, during, and after SEEG could decrease the risk of development or worsening of symptoms of anxiety, depression, and posttraumatic stress disorder.