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In the neocortex, ~90 Hz ripples couple to ~12 Hz sleep spindles on the ~1 Hz Down-to-Up state transition during non-rapid eye movement sleep. This conjunction of sleep waves is critical for the consolidation of memories into long-term storage. The widespread co-occurrences of ripples ("co-ripples") may integrate information across the neocortex and hippocampus to facilitate consolidation. While the thalamus synchronizes spindles and Up states in the cortex for memory, it is not known whether it may also organize co-ripples. Using human intracranial recordings during NREM sleep, we investigated whether cortico-cortical co-ripples and hippocampo-cortical co-ripples are either: (1) driven by directly projected thalamic ripples; or (2) coordinated by propagating thalamic spindles or Up states. We found ripples in the anterior and posterior thalamus, with similar characteristics as hippocampal and cortical ripples, including having a center frequency of ~90 Hz and coupling to local spindles on the Down-to-Up state transition. However, thalamic ripples rarely co-occur or phase-lock with cortical or hippocampal ripples. By contrast, spindles and Up states that propagate from the thalamus strongly coordinate co-ripples in the cortex and hippocampus. Thus, thalamo-cortical spindles and Up states, rather than thalamic ripples, may provide input facilitating spatially distributed co-rippling that integrates information for memory consolidation during sleep in humans. The thalamus synchronizes spindles and Up states in the cortex for memory, but does it also organize co-ripples in the hippocampus and neocortex? This study shows that during human sleep, thalamic spindles and Up states synchronize networks that regulate memory consolidation during sleep. [ABSTRACT FROM AUTHOR]

Objective: Sudden unexpected death in epilepsy (SUDEP) is a serious threat to individuals with intractable epilepsies, contributing to premature mortality. Understanding the elusive pathophysiological mechanisms of SUDEP, especially in cases without observable terminal events, remains a crucial area for investigation. This study aimed to shed light on the burden of epileptiform activity preceding SUDEP by utilizing an automated electronic seizure diary derived from a sensing‐enabled thalamic deep brain stimulator (DBS). Methods: Herein, we present the case of a 57‐year‐old man afflicted with intractable multifocal epilepsy secondary to cortical dysplasia and encephalomalacia resulting from severe traumatic brain injury. Despite an initial successful resection and subsequent resurgence of seizures necessitating DBS treatment, the patient tragically succumbed to SUDEP. Results: In‐depth analysis of the patient's electronic seizure diary, complemented by data from the sensing‐enabled DBS, unveiled a terminal electrographic seizure. Notably, we observed a significant increase in power within specific frequency bands recorded from the thalamus preceding the terminal event. Furthermore, these heightened band power events displayed a discernible temporal clustering pattern, primarily manifesting during specific morning and evening hours. An autopsy conclusively confirmed the diagnosis of definite SUDEP. Interpretation: This unique case report underscores the feasibility of harnessing thalamic DBS sensing capabilities to monitor seizure burden and, potentially, to tailor interventions aimed at reducing seizure frequency and associated mortality risks. [ABSTRACT FROM AUTHOR]

Objective: Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco‐resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo‐electroencephalography (SEEG) ‐informed magnetic resonance‐guided laser interstitial thermal therapy (MRgLITT). Methods: A retrospective review of consecutive cases from a single high‐volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes. Results: Thirty‐nine patients underwent SEEG‐guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow‐up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p < 0.001). Interpretation: PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH‐associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024;96:1174–1184 [ABSTRACT FROM AUTHOR]

BACKGROUND Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. MATERIAL AND METHODS A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). RESULTS After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=-0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=-0.357; p=0.103) and left posterior limb of the internal capsule (R=-0.319; p=0.148). CONCLUSIONS Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity.

Objective: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. Methods: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact‐free respiratory signal were analyzed. Results: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3–11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high‐frequency broadband gamma (60–150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4‐fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset‐synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. Interpretation: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998–1008 [ABSTRACT FROM AUTHOR]

Objective: Stereo‐electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure‐onset zone (SOZ) in drug‐resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre‐implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two‐step SEEG – 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two‐step intracranial EEG (iEEG). Methods: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two‐step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two‐step iEEG benefit and clinical outcome was then analyzed. Results: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons—precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non‐localizable seizure onsets (43% of cases). Sixty‐four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p =.02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. Significance: The two‐step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal‐onset zones and eloquent cortex. [ABSTRACT FROM AUTHOR]

Objective: We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing. Methods: Twenty‐nine patients with medically intractable epilepsy were prospectively recruited in an epilepsy monitoring unit while undergoing stereoelectroencephalographic evaluation. Direct electrical stimulation in cortical and thalamic regions was carried out using low (<1 Hz) and high (≥10 Hz) frequencies, and low (<5 mA) and high (≥5 mA) current intensities, with pulse width of.1 ms. Electrocardiography, arterial oxygen saturation (SpO2), end‐tidal carbon dioxide (ETCO2), oronasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. Airflow signal was used to estimate breathing rate, tidal volume, and minute ventilation (MV) changes during stimulation, compared to baseline. Results: Electrical stimulation increased MV in the amygdala, anterior cingulate, anterior insula, temporal pole, and thalamus, with an average increase in MV of 20.8% ± 28.9% (range = 0.2%–165.6%) in 19 patients. MV changes were associated with SpO2 and ETCO2 changes (p <.001). Effects on respiration were parameter and site dependent. Within amygdala, low‐frequency stimulation of the medial region produced 78.49% greater MV change (p <.001) compared to high‐frequency stimulation. Longer stimulation produced greater MV changes (an increase of 4.47% in MV for every additional 10 s, p =.04). Significance: Stimulation of amygdala, anterior cingulate gyrus, anterior insula, temporal pole, and thalamus, using certain stimulation paradigms, enhances respiration. Among tested paradigms, low‐frequency, low‐intensity, long‐duration stimulation of the medial amygdala is the most effective breathing enhancement stimulation strategy. Such approaches may pave the way for the future development of neuromodulatory techniques that aid rescue from seizure‐related apnea, potentially as a targeted sudden unexpected death in epilepsy prevention method. [ABSTRACT FROM AUTHOR]

Loss of complexity and chaos of heart rate variability (HRV) of an individual increases the risk of mortality from cardiovascular diseases. Abnormalities in HRV associated with intractable epilepsy may even lead to "sudden death in epilepsy" (SUDEP). By activating the parasympathetic division of the autonomic nervous system, Vagus Nerve Stimulation (VNS) has the potential to restore the natural chaotic behavior of the heart which can be measured by the increase in complexity of HRV as indicated by complexity measures such as Effort-To-Compress (ETC) and Lempel-Ziv Complexity (LZC). In this study, we formulate and test two hypothesis – (A) chaotic time series exhibit lower temporal correlation of complexity measures such as LZ and ETC than uniformly random time series, and (B) Vagus Nerve Stimulation (VNS ON) results in chaotic cardiovascular dynamics. Hypothesis-A is verified by a simulated study on chaotic time series from the Logistic map where we see a clear decrease in temporal correlation between ETC and LZC values as the degree of chaos increases. Hypothesis-B is supported by an experimental study on a VNS implanted patient and not implanted controls. A temporal correlation analysis between complexity measures (ETC and LZC) on HRV data samples shows that VNS during sleep increases chaotic behavior in contrast to lack of VNS and in control subjects. Surrogate analysis further confirmed that VNS activation led to deterministic chaos and not stochastic randomness. Our approach proposes a clear methodology to determine the efficacy of VNS intervention in restoring the chaoticity of cardiovascular dynamics. [ABSTRACT FROM AUTHOR]