In patients with medically refractory epilepsy, resective surgery is the mainstay of therapy to achieve seizure freedom. However, ∼20-50% of cases have intractable seizures post-surgery due to the ...imprecise determination of epileptogenic zone. Recent intracranial studies suggest that high frequency oscillations between 80 and 200 Hz could serve as one of the consistent epileptogenicity biomarkers for localization of the epileptogenic zone. However, these high frequency oscillations are not adopted in the clinical setting because of difficult non-invasive detection. Here, we investigated non-invasive detection and localization of high frequency oscillations and its clinical utility in accurate pre-surgical assessment and post-surgical outcome prediction. We prospectively recruited 52 patients with medically refractory epilepsy who underwent standard pre-surgical workup including magnetoencephalography (MEG) followed by resective surgery after determination of the epileptogenic zone. The post-surgical outcome was assessed after 22.14 ± 10.05 months. Interictal epileptic spikes were expertly identified, and interictal epileptic oscillations across the neural activity frequency spectrum from 8 to 200 Hz were localized using adaptive spatial filtering methods. Localization results were compared with epileptogenic zone and resected cortex for congruence assessment and validated against the clinical outcome. The concordance rate of high frequency oscillations sources (80-200 Hz) with the presumed epileptogenic zone and the resected cortex were 75.0% and 78.8%, respectively, which is superior to that of other frequency bands and standard dipole fitting methods. High frequency oscillation sources corresponding with the resected cortex, had the best sensitivity of 78.0%, positive predictive value of 100% and an accuracy of 78.84% to predict the patient's surgical outcome, among all other frequency bands. If high frequency oscillation sources were spatially congruent with resected cortex, patients had an odds ratio of 5.67 and 82.4% probability of achieving a favourable surgical outcome. If high frequency oscillations sources were discordant with the epileptogenic zone or resection area, patient has an odds ratio of 0.18 and only 14.3% probability of achieving good outcome, and mostly tended to have an unfavourable outcome (χ2 = 5.22; P = 0.02; φ = -0.317). In receiver operating characteristic curve analyses, only sources of high-frequency oscillations demonstrated the best sensitivity and specificity profile in determining the patient's surgical outcome with area under the curve of 0.76, whereas other frequency bands indicate a poor predictive performance. Our study is the first non-invasive study to detect high frequency oscillations, address the efficacy of high frequency oscillations over the different neural oscillatory frequencies, localize them and clinically validate them with the post-surgical outcome in patients with medically refractory epilepsy. The evidence presented in the current study supports the fact that HFOs might significantly improve the presurgical assessment, and post-surgical outcome prediction, where it could widely be used in a clinical setting as a non-invasive biomarker.
Highlights • EEG of 9 patients with absence epilepsy were evaluated for occurrence of HFO. • HFOs were associated with inter-ictal generalized (241/454). • HFOs were associated with ictal generalized ...(634/884). • HFOs were associated with sporadic spike-wave discharges (51/100). • ICA with spectral analysis showed the mean frequency of HFOs was 96.4 ± 10.4 Hz.
Highlights • Source localization of MEG epileptiform discharges in 20 patients with JME was done. • Source analysis was performed at onset, peak and offset of discharges. • Localization at onset was ...sublobar region, at peak from frontal lobe and at offset from the sublobar region. • It indicated restricted cortical-subcortical involvement during the generation and propagation of EDs in JME.
•Patients with eating epilepsy show a disrupted network during resting state. During eating, they tend towards a hyperconnected state with deviations from small worldness.•Patients with spontaneous ...seizures show a deviation from small worldness even in a resting state compared to those with pure reflex seizures.•Connectivity changes in resting state networks Default Mode Network, Attention network, sensorimotor networks were observed in resting state records of patients with eating epilepsy compared to controls.•Connectivity changes during eating involved the default mode network nodes, limbic cortex, and nodes participating in the physiological process of eating.
Eating epilepsy presents various imaging and electrophysiological features along with various seizure triggers. As such, network changes in eating epilepsy have not been comprehensively explored. This study was conducted to illustrate resting state network changes in eating epilepsy and to study the changes in network configurations during eating.
Magnetoencephalography recordings of nineteen patients with drug-resistant eating epilepsy were compared with healthy controls during resting state. A subgroup of nine patients and 12 controls had MEG recordings during eating. Network changes were analyzed using phase lag index across 5 frequency bands delta, theta, alpha, beta, and gamma using clustering coefficient (CC), betweenness centrality (BC), path length (PL), modularity (Q), and small worldness (SW).
During the resting state, PL was decreased in patients with epilepsy in the delta, theta, and gamma band. Q was lower in patients with epilepsy in the beta and gamma bands. During eating, in patients with epilepsy, PL and SW were increased in all frequency bands, and Q was decreased in the beta band and increased in the rest of the frequency bands. Patients with mixed types of seizures showed higher PL in all bands except alpha, higher Q in all bands, and higher SW in the alpha and beta bands. Node-wise changes in CC and BC implicated changes in DMN and ‘eating’ networks.
Reflex Eating epilepsy presents with a hyperconnected network that exacerbates during eating. The cause of seizure onset and loss of consciousness in eating epilepsy might be due to aberrant network interaction between the regions of the brain involved with eating, such as the sensorimotor cortex, lateral parietal cortex, and insula with the limbic cortex and default mode network across multiple frequency bands.
Background
Transcranial direct current stimulation (tDCS) is a safe non‐invasive brain stimulation (NIBS) procedure which helps to stimulate a particular region of interest by modulating the neuronal ...firing rate, thereby modulating the cognitive functioning. The tDCS intervention is known to show improvement on memory recall and recognition in patients with mild cognitive impairment (MCI) and mild Alzheimer’s Disease (mild AD)
Method
We investigated the effect of anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation at the right supra‐orbital area in patients with MCI (n = 18) and mild AD (n = 20) (Refer Table 1), after due approval from Institute Ethics Committee NIMHANS. Both baseline and post‐intervention assessments for a single patient were administered by the different assessors allocated randomly using NIMHANS neuropsychological battery for elderly (NNB‐E). Two resting state functional magnetic resonance imaging (rsfMRI) acquisitions, before and after the ten sessions of tDCS, each session lasting 20 minutes. A spherical mask of 5 mm diameter was chosen a priori on the left middle frontal gyrus (LMFG) as a seed for performing seed based functional connectivity (sbFC) analysis using default preprocessing pipeline and pre‐post analysis setup in CONN 18b toolbox.
Result
The combined sample of patients with MCI and mild AD showed significant improvement in word list learning trial 3 (pre tDCS 5.85 (1.59); post tDCS 6.63 (1.67); Z = 3.586, p<0.0001) and delayed recall (pre tDCS 1.50 (1.88); post tDCS 2.45 (2.33); Z = 3.656, p<0.0001) scores using NNB‐E. The sbFC analysis showed significantly reduced functional connectivity between left MFG (the region of anodal stimulation) and posterior cingulate cortex (PCC) as well as precuneus cortex (cluster‐level extent threshold p‐FDR <0.05) after tDCS. Post‐hoc tests showed that these reductions after tDCS intervention were also found to be significantly associated with attention and auditory verbal learning memory scores (Refer Figure 1 and Table 2).
Conclusion
The tDCS intervention helped reducing the functional connectivity at rest, which was responsible for compensatory neuronal processes found in early AD. These findings unravel the therapeutic role of tDCS by enhancing auditory verbal memory performance and altering the functional connectivity at PCC and precuneus cortex in earlier stages of AD.
Study assessed the role of MSI in predicting the post-operative seizure outcome.
This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of ...postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed.
A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up.
The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool.
Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls.
We performed a ...retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated.
During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range IQR = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency.
Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks.
Summary
Objective
Specificity of ictal high‐frequency oscillations (HFOs) in identifying epileptogenic abnormality is significant, compared to the spikes and interictal HFOs. The objectives of the ...study were to detect and to localize ictal HFOs by magnetoencephalography (MEG) for identifying the seizure onset zone (SOZ), evaluate the cortical excitability from preictal to ictal transition, and establish HFO concordance rates with other modalities and postsurgical resection.
Methods
Sixty‐seven patients with drug‐resistant epilepsy had at least 1 spontaneous seizure each during MEG acquisition, and analysis was carried out on 20 seizures from 20 patients. Ictal MEG data were bandpass filtered (80‐200 Hz) to visualize, review, and analyze the HFOs co‐occurring with ictal spikes. Source montages were generated on both hemispheres, mean fast Fourier transform was computed on virtual time series for determining the preictal to ictal spectral power transition, and source reconstruction was performed with sLORETA and beamformers. The concordance rates of ictal MEG HFOs (SOZ) was estimated with 4 reference epileptogenic regions.
Results
In each subject, transient bursts of high‐frequency oscillatory cycles, distinct from the background activity, were observed in the periictal continuum. Time‐frequency analysis showed significant spectral power surge (85‐160 Hz) during ictal state (P < .05) compared to preictal state, but there was no variation in the peak HFO frequencies (P > .05) for each subgroup and at each source montage. HFO source localization was consistent between algorithms (k = 0.857 ± 0.138), with presumed epileptogenic zone (EZ) comparable to other modalities. In patients who underwent surgery (n = 6), MEG HFO SOZ was concordant with the presumed EZ and the surgical resection site (100%), and all were seizure‐free during follow‐up.
Significance
HFOs could be detected in the MEG periictal state, and its sources were accurately localized. During preictal to ictal transition, HFOs exhibited dynamic augmentation in intrinsic epileptogenicity. Spatial overlap of ictal HFO sources was consistent with EZ determinants and the surgical resection area.
Background
Working memory and executive function deficits are the characteristic features of Mild Cognitive Impairment and mild Alzheimer’s Disease (mild AD). Studies exploring the alterations in ...working memory and executive functions show disrupted functional connectivity in Dorsolateral Pre Frontal Cortices (DLPFC) and Angular Gyrus (AG). Transcranial direct current stimulation (tDCS), by stimulating these brain regions, can alter resting‐state functional connectivity (rs‐FC) and has emerged as a safe and non‐invasive technique that has the potential to enhance neuroplasticity and cognitive improvement.
Method
We investigated the effect of anodal stimulation at the left DLPFC and cathode placed at the right supra‐orbital area to observe the rsFC changes in patients with MCI and mild AD (n=12; Age=67.58 ± 8.59 years, Gender ratio 1:1, formal years of education= 14.58±3.55 years, Hindi mental Status examination=26.91±3.1), who attended the outpatient services of Geriatric Clinic and Services, after due approval from institute ethics committee NIMHANS. The resting‐state functional magnetic resonance imaging (rsfMRI) acquisitions were performed before and after the ten sessions of tDCS, each session lasting 20 minutes. Investigations were performed on subregions of DLPFC (left Superior Frontal Gyrus (LSFG), Right SFG, left Middle Frontal Gyrus (LMFG) and Right MFG) and Angular Gyrus (Right Angular Gyrus (RAG) and Left AG), chosen a priori as seeds for the seed based FC (sbFC) analysis after correcting for the influences of age and gender using CONN 18b toolbox. Spherical masks of size 5 mm diameter were also created for the above‐mentioned seeds.
Result
The pre‐post tDCS comparisons of sbFC showed significant (FDR; p<0.05) reduction of rsFC in patients with MCI and mild AD at right supramarginal gyrus, right angular gyrus, right frontal pole (for Seed‐RAG, Voxel‐ whole brain), supramarginal gyrus (for Seed‐RAG, Voxel‐ RAG), and Middle Temporal gyrus, left Temporo‐Occipital part (for Seed‐ RSFG, Voxel‐ whole brain) as shown in Figure 1 a, b, and c respectively (Refer Table 1).
Conclusion
The results support that anodal stimulation using tDCS at left DLPFC may lead to the reduction of aberrantly increased functional connectivity between brain regions involved in working memory and executive functions in MCI and mild AD.
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