The normal physiological intracranial EEG has not been fully characterised. Frauscher et al. develop a 3D atlas that describes the normal intracranial EEG during wakefulness. The atlas provides a ...normative baseline against which clinical EEGs and experimental results can be compared. It is available as an open web resource.
Abstract
In contrast to scalp EEG, our knowledge of the normal physiological intracranial EEG activity is scarce. This multicentre study provides an atlas of normal intracranial EEG of the human brain during wakefulness. Here we present the results of power spectra analysis during wakefulness. Intracranial electrodes are placed in or on the brain of epilepsy patients when candidates for surgical treatment and non-invasive approaches failed to sufficiently localize the epileptic focus. Electrode contacts are usually in cortical regions showing epileptic activity, but some are placed in normal regions, at distance from the epileptogenic zone or lesion. Intracranial EEG channels defined using strict criteria as very likely to be in healthy brain regions were selected from three tertiary epilepsy centres. All contacts were localized in a common stereotactic space allowing the accumulation and superposition of results from many subjects. Sixty-second artefact-free sections during wakefulness were selected. Power spectra were calculated for 38 brain regions, and compared to a set of channels with no spectral peaks in order to identify significant peaks in the different regions. A total of 1785 channels with normal brain activity from 106 patients were identified. There were on average 2.7 channels per cm3 of cortical grey matter. The number of contacts per brain region averaged 47 (range 6-178). We found significant differences in the spectral density distributions across the different brain lobes, with beta activity in the frontal lobe (20-24 Hz), a clear alpha peak in the occipital lobe (9.25-10.25 Hz), intermediate alpha (8.25-9.25 Hz) and beta (17-20 Hz) frequencies in the parietal lobe, and lower alpha (7.75-8.25 Hz) and delta (0.75-2.25 Hz) peaks in the temporal lobe. Some cortical regions showed a specific electrophysiological signature: peaks present in >60% of channels were found in the precentral gyrus (lateral: peak frequency range, 20-24 Hz; mesial: 24-30 Hz), opercular part of the inferior frontal gyrus (20-24 Hz), cuneus (7.75-8.75 Hz), and hippocampus (0.75-1.25 Hz). Eight per cent of all analysed channels had more than one spectral peak; these channels were mostly recording from sensory and motor regions. Alpha activity was not present throughout the occipital lobe, and some cortical regions showed peaks in delta activity during wakefulness. This is the first atlas of normal intracranial EEG activity; it includes dense coverage of all cortical regions in a common stereotactic space, enabling direct comparisons of EEG across subjects. This atlas provides a normative baseline against which clinical EEGs and experimental results can be compared. It is provided as an open web resource (https://mni-open-ieegatlas.research.mcgill.ca).
Summary
Purpose
Simultaneous electroencephalography/functional magnetic resonance imaging (EEG/fMRI) recording can noninvasively map in the whole brain the hemodynamic response following an ...interictal epileptic discharge. EEG/fMRI is gaining interest as a presurgical evaluation tool. This study aims to determine how hemodynamic responses related to epileptic activity can help predict surgical outcome in patients considered for epilepsy surgery.
Methods
Thirty‐five consecutive patients with focal epilepsy who had significant hemodynamic responses and eventually surgical resection, were studied. The statistical map of hemodynamic responses were generated and coregistered to postoperative anatomic imaging. Patients were classified into four groups defined by the relative relationship between the location of the maximum hemodynamic response and the resection: group 1, fully concordant; group 2, partially concordant; group 3, partially discordant; and group 4, fully discordant. These findings were correlated with surgical outcome with at least 12‐month follow‐up.
Key Findings
Ten patients in group 1 had the maximum t value (t‐max) inside the resection; nine in group 2 had the t‐max outside but close to the resection and the cluster with t‐max overlapped the resection; five in group 3 had the t‐max remote from resection, but with another less significant cluster in the resection; and 11 in group 4 had no response in the resection. The degree of concordance correlated largely with surgical outcome: a good surgical outcome (Engel's class I) was found in 7 of 10 patients of group 1, 4 of 9 of group 2, 3 of 5 of group 3, and only 1 of 11 of group 4. These results indicate that the partially concordant and partially discordant groups are best considered as inconclusive. In contrast, in the fully concordant and fully discordant groups, the sensitivity, specificity, positive predictive value, and negative predictive value were high, 87.5%, 76.9%, 70%, and 90.9%, respectively.
Significance
This study demonstrates that hemodynamic responses related to epileptic activity can help delineate the epileptogenic region. Full concordance between maximum response and surgical resection is indicative of seizure freedom, whereas a resection leaving the maximum response intact is likely to lead to a poor outcome. EEG/fMRI is noninvasive but is limited to patients in whom interictal epileptic discharges can be recorded during the 60–90 min scan.
High frequency oscillations (HFOs) called ripples (80–250 Hz) and fast ripples (FR, 250–500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs ...occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80–250 Hz) and Fast Ripples (250–500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.
The increasing use of plant defense stimulators (PDS) and biostimulants (BS) to make agriculture more sustainable has led to questions about their action on plants. A new PhysBioGen approach is ...proposed with complementary tools: PHYSiological (root weight); BIOchemical and BIOlogical (secondary metabolite quantification and Plasmopara viticola development) and expressions of 161 GENes involved in metabolic plant functions. The proposed approach investigated the effects of three phytostimulants on Vitis vinifera: one PDS (ASM) and one BS chelated (CH) and another enriched with seaweed (SW). Distinct responses were obtained between the PDS and the two BS. In particular, we observed the persistence of anti-mildew efficacy over time, correlated with differentiated expressions of defense genes (VvROMT, VvSAMT, VvPR8). As expected, the two BS displayed more similarities to each other than to the PDS (flavonols, anthocyanins, free salicylic acid). However, the two BS revealed differences in the modulation of genes involved in defense and primary metabolism and some genes were identified as potential markers of their action (VvWRKY1, VvLOX9, VvPOD, VvPDV1, VvXIP1, VVDnaJ). Our results highlight the common and the specific effects of the two BS and the PDS. These new tools could help in understanding the mode of action of phytostimulants in order to achieve better quality and production yield and/or as a way to limit chemical inputs in the vineyard.
• Molecular signals released by microbes at the surface of plant roots and leaves largely determine host responses, notably by triggering either immunity or symbiosis. How these signalling pathways ...cross-talk upon coincident perception of pathogens and symbionts is poorly described in plants forming symbiosis.
• Nitrogen fixing symbiotic Rhizobia spp. and arbuscular mycorrhizal fungi produce lipochitooligosaccharides (LCOs) to initiate host symbiotic programmes. In Medicago truncatula roots, the perception of LCOs leads to reduced efflux of reactive oxygen species (ROS). By contrast, pathogen perception generally triggers a strong ROS burst and activates defence gene expression.
• Here we show that incubation of M. truncatula seedlings with culture filtrate (CF) of the legume pathogen Aphanomyces euteiches alone or simultaneously with Sinorhizobium meliloti LCOs, resulted in a strong ROS release. However, this response was completely inhibited if CF was added after pre-incubation of seedlings with LCOs. By contrast, expression of immunity-associated genes in response to CF and disease resistance to A. euteiches remained unaffected by LCO treatment of M. truncatula roots.
• Our findings suggest that symbiotic plants evolved ROS inhibition response to LCOs to facilitate early steps of symbiosis whilst maintaining a parallel defence mechanisms toward pathogens.
Summary
Purpose
Removal of areas generating high‐frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been ...found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO‐generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome.
Methods
We studied 30 patients with drug‐resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow‐up was extended. All patients underwent iEEG investigations (500 Hz high‐pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure‐onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome.
Key Findings
HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome.
Significance
In TLE, removal of HFO‐generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.
The authors sought to determine which neurophysiological seizure-onset features seen during scalp electroencephalography (EEG) and intracerebral EEG (iEEG) monitoring are predictors of postoperative ...outcome in a large series of patients with drug-resistant focal epilepsy who underwent resective surgery.
The authors retrospectively analyzed the records of 75 consecutive patients with focal epilepsy, who first underwent scalp EEG and then iEEG (stereo-EEG) for presurgical assessment and who went on to undergo resective surgery between 2004 and 2015. To determine the independent prognostic factors from the neurophysiological scalp EEG and iEEG seizure-onset information, univariate and standard multivariable logistic regression analyses were used. Since scalp EEG and iEEG data were recorded at different times, the authors matched scalp seizures with intracerebral seizures for each patient using strict criteria.
A total of 3057 seizures were assessed. Forty-eight percent (36/75) of patients had a favorable outcome (Engel class I-II) after a minimum follow-up of at least 1 year. According to univariate analysis, a localized scalp EEG seizure onset (p < 0.001), a multilobar intracerebral seizure-onset zone (SOZ) (p < 0.001), and an extended SOZ (p = 0.001) were significantly associated with surgical outcome. According to multivariable analysis, the following two independent factors were found: 1) the ability of scalp EEG to localize the seizure onset was a predictor of a favorable postoperative outcome (OR 6.073, 95% CI 2.011-18.339, p = 0.001), and 2) a multilobar SOZ was a predictor of an unfavorable outcome (OR 0.076, 95% CI 0.009-0.663, p = 0.020).
The study findings show that localization at scalp seizure onset and a multilobar SOZ were strong predictors of surgical outcome. These predictors can help to select the better candidates for resective surgery.
Summary
Objective
Intracranial electroencephalography (EEG), performed presurgically in patients with drug‐resistant and difficult‐to‐localize focal epilepsy, samples only a small fraction of brain ...tissue and thus requires strong hypotheses regarding the possible localization of the epileptogenic zone. EEG/fMRI (functional magnetic resonance imaging), a noninvasive tool resulting in hemodynamic responses, could contribute to the generation of these hypotheses. This study assessed how these responses, despite their interictal origin, predict the seizure‐onset zone (SOZ).
Methods
We retrospectively studied 37 consecutive patients who underwent stereo‐EEG (SEEG) and EEG/fMRI that resulted in significant hemodynamic responses. Hemodynamic response maps were co‐registered to postimplantation anatomic imaging, allowing inspection of these responses in relation to SEEG electrode's location. The area containing the most significant t‐value (primary cluster) explored with an electrode was assessed for concordance with SEEG‐defined SOZ. Discriminant analysis was performed to distinguish the primary clusters having a high probability of localizing the SOZ.
Results
Thirty‐one patients had at least one study with primary cluster explored with an electrode, and 24 (77%) had at least one study with primary cluster concordant with the SOZ. Each patient could have multiple types of interictal discharge and therefore multiple studies. Among 59 studies from the 37 patients, 44 had a primary cluster explored with an electrode and 30 (68%) were concordant with the SOZ. Discriminant analysis showed that the SOZ is predictable with high confidence (>90%) if the primary cluster is highly significant and if the next significant cluster is much less significant or absent.
Significance
The most significant hemodynamic response to interictal discharges delineates the subset of the irritative zone that generates seizures in a high proportion of patients with difficult‐to‐localize focal epilepsy. EEG/fMRI generates responses that are valuable targets for electrode implantation and may reduce the need for implantation in patients in whom the most significant response satisfies the condition of our discriminant analysis.
Arbuscular mycorrhizal (AM) symbiosis associates most plants with fungi of the phylum Glomeromycota. The fungus penetrates into roots and forms within cortical cell branched structures called ...arbuscules for nutrient exchange. We discovered that miR171b has a mismatched cleavage site and is unable to downregulate the miR171 family target gene, LOM1 (LOST MERISTEMS 1). This mismatched cleavage site is conserved among plants that establish AM symbiosis, but not in non-mycotrophic plants. Unlike other members of the miR171 family, miR171b stimulates AM symbiosis and is expressed specifically in root cells that contain arbuscules. MiR171b protects LOM1 from negative regulation by other miR171 family members. These findings uncover a unique mechanism of positive post-transcriptional regulation of gene expression by miRNAs and demonstrate its relevance for the establishment of AM symbiosis.
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•miR171b is specific to mycotrophic species and has a target gene cleavage site mismatch•miR171b accumulation activated target gene LOM1 expression and enhanced mycorrhization•miR171b is preferentially expressed in arbuscule-containing cells•miR171b expression protects LOM1 from silencing by other miR171 family members
Arbuscular mycorrhizal symbiosis, a plant-fungal mutualistic relationship, is regulated by the miR171 family. Couzigou et al. discover that miR171b has evolved a target site mismatch such that instead of silencing, miR171b protects its target gene LOM1 from cleavage by other miR171 family members and thereby enables AM symbiosis.
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