How does upper extremity Fugl-Meyer motor score relate to resting-state EEG in chronic stroke? A power spectral density analysis

ObjectiveWe investigated the potential added value of high-density resting-state EEG by addressing differences with healthy individuals and associations with Fugl-Meyer motor assessment of the upper extremity (FM-UE) scores in chronic stroke.MethodsTwenty-one chronic stroke survivors with initial upper limb paresis and eleven matched controls were included. Group differences regarding resting-state EEG parameters (Delta Alpha ratio (DAR) and pairwise-derived Brain Symmetry Index (BSI)) and associations with FM-UE were investigated, as well as lateralization of BSI and the value of different frequency bands.ResultsChronic stroke survivors showed higher BSI compared to controls (p < 0.001), most pronounced in delta and theta frequency bands (p < 0.0001; p < 0.001). In the delta and theta band, BSI was significantly negatively associated with FM-UE (both p = 0.008) corrected for confounding factors. DAR showed no differences between groups nor association with FM-UE. Directional BSI showed increased power in the affected versus the unaffected hemisphere.ConclusionsAsymmetry in spectral power between hemispheres was present in chronic stroke, most pronounced in low frequencies and related to upper extremity motor function deficit.SignificanceBSI is related to motor impairment and higher in chronic stroke patients compared to healthy controls, suggesting that BSI may be a marker of selective motor control.     

Family nurture intervention alters relationships between preterm infant EEG delta brush characteristics and term age EEG power

ObjectiveFamily Nurture Intervention (FNI) facilitates mother/infant emotional connection, improves neurodevelopmental outcomes and increases electroencephalogram (EEG) power at term age. Here we explored whether delta brushes (DB), early EEG bursts that shape brain development, are altered by FNI and mediate later effects of FNI on EEG.MethodsWe assessed DB characteristics in EEG data from a randomized controlled trial comparing infants with standard care (SC, n = 31) versus SC + FNI (n = 33) at ~35 and ~40 weeks GA.ResultsCompared to SC infants, FNI infant DB amplitude increased more from ~35 to ~40 weeks, and FNI infants had longer duration DBs. DB parameters (rate, amplitude, brush frequency) at ~35 weeks were correlated with power at ~40 weeks, but only in SC infants. FNI effects on DB parameters do not mediate FNI effects on EEG power or coherence at term.ConclusionsDBs are related to subsequent brain activity and FNI alters DB parameters. However, FNI’s effects on electrocortical activity at term age are not dependent on its earlier effects on DBs.SignificanceWhile early DBs can have important effects on later brain activity in preterm infants, facilitating emotional connection with FNI may allow brain maturation to be less dependent on early bursts.     

Unaltered EEG spectral power and functional connectivity in REM microstates in frequent nightmare recallers: are nightmares really a REM parasomnia?

BackgroundFrequent nightmares show signs of hyperarousal in NREM sleep. Nevertheless, idiopathic nightmare disorder is considered a REM parasomnia, but the pathophysiology of REM sleep in relation to frequent nightmares is controversial. Cortical oscillatory activity in REM sleep is largely modulated by phasic and tonic REM periods and seems to be linked to different functions and dysfunctions of REM sleep. Here, we examined cortical activity and functional synchronization in frequent nightmare recallers and healthy controls, during phasic and tonic REM.MethodsFrequent nightmare recallers (N = 22) and healthy controls (N = 22) matched for high dream recall spent two nights in the laboratory. Phasic and tonic REM periods from the second nights' recordings were selected to examine differences in EEG spectral power and weighted phase lag index (WPLI) across groups and REM states.ResultsPhasic REM showed increased power and synchronization in delta and gamma frequency bands, whereas tonic REM featured increased power and synchronization in the alpha and beta bands. In the theta band, power was higher during tonic, and synchronization was higher during phasic REM sleep. No differences across nightmare and control participants or patterns representing interactions between the groups and REM microstates emerged.ConclusionsOur findings do not support the idea that abnormal REM sleep power and synchronization play a role in the pathophysiology of frequent nightmares. Altered REM sleep in nightmare disorder could have been confounded with comorbid pathologies and increased dream recall, or might be linked to more specific state factors (nightmare episodes).     

High-amplitude fast activity in EEG: An early diagnostic marker in children with beta-propeller protein-associated neurodegeneration (BPAN)

ObjectiveThe early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 μV) fast activity (HAFA) on electroencephalography (EEG).MethodsWe conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11). Trained electroencephalographers reviewed all of the EEGs. When excessive fast activity was observed, the amplitude, frequency, and locality were assessed.ResultsAll five patients with BPAN underwent initial EEGs at 12–21 months old, and diffuse continuous HAFA (range 20–50 Hz) was observed on both awake and sleep EEGs. In the awake records, there was no clear posterior dominant rhythm in 4 of the 5 patients. Although 28% of the 143 EEGs had continuous excessive fast activity, mainly in the sleep records, only two (1.4%) exhibited HAFA when asleep, and their awake EEGs had clear posterior dominant rhythm.ConclusionsThe EEGs of children with BPAN showed diffuse HAFA continuously when both awake and asleep, which is uncommon in children with other etiologies.SignificanceThis study provides an important clue for the early diagnosis of BPAN.     

Electroencephalography complexity in infantile spasms and its association with treatment response

ObjectiveTo investigate the potential of EEG multiscale entropy and complexity as biomarkers in infantile spasms.MethodsWe collected EEG data retrospectively from 16 newly diagnosed patients, 16 age- and gender-matched healthy controls, and 15 drug-resistant patients. The multiscale entropy (MSE) and total EEG complexity before anti-epileptic drug (AED) treatment, before adrenocorticotropic hormone (ACTH) treatment, 14 days after ACTH therapy, and after 6 months of follow-up were calculated.ResultsThe total EEG complexity of 16 newly diagnosed infantile spasms patients was lower than the 16 healthy controls (median [IQR]: 351.5 [323.1–388.1] vs 461.6 [407.7–583.4]). The total EEG complexity before treatment was higher in the six patients with good response to AED than the 10 patients without response (median [IQR]: 410.0 [388.1–475.0] vs 344.5 [319.6–352.0]). The total EEG complexity before and after 14-days of ACTH therapy was not different between 13 ACTH therapy responders and nine non-responders. After 6-months follow-up, the total EEG complexity of ACTH therapy responders were higher than non-responders (median [IQR]: 598.5 [517.4–623.3] vs 448.6 [347.1–536.3]).ConclusionsThe total EEG complexity before AED and 6 months after ACTH are associated with spasm-freedom.SignificanceThe total EEG complexity is a potential biomarker to predict and monitor the treatment effect in infantile spasms.     

Automated electrical source imaging with scalp EEG to define the insular irritative zone: Comparison with simultaneous intracranial EEG

Objective To evaluate the accuracy of automated interictal low-density electrical source imaging (LD-ESI) to define the insular irritative zone (IZ) by comparing the simultaneous interictal ESI localization with the SEEG interictal activity.Methods Long-term simultaneous scalp electroencephalography (EEG) and stereo-EEG (SEEG) with at least one depth electrode exploring the operculo-insular region(s) were analyzed. Automated interictal ESI was performed on the scalp EEG using standardized low-resolution brain electromagnetic tomography (sLORETA) and individual head models. A two-step analysis was performed: i) sublobar concordance between cluster-based ESI localization and SEEG-based IZ; ii) time-locked ESI-/SEEG analysis. Diagnostic accuracy values were calculated using SEEG as reference standard. Subgroup analysis was carried out, based on the involvement of insular contacts in the seizure onset and patterns of insular interictal activity.Results Thirty patients were included in the study. ESI showed an overall accuracy of 53% (C.I. 29–76%). Sensitivity and specificity were calculated as 53% (C.I. 29–76%), 55% (C.I. 23–83%) respectively. Higher accuracy was found in patients with frequent and dominant interictal insular spikes.Conclusions LD-ESI defines with good accuracy the insular implication in the IZ, which is not possible with classical interictal scalp EEG interpretation.SignificanceAutomated LD-ESI may be a valuable additional tool to characterize the epileptogenic zone in epilepsies with suspected insular involvement.     

A standardized nomenclature for spectrogram EEG patterns: Inter-rater agreement and correspondence with common intensive care unit EEG patterns

ObjectiveTo determine the inter-rater agreement (IRA) of a standardized nomenclature for EEG spectrogram patterns, and to estimate the probability distribution of ictal-interictal continuum (IIC) patterns vs. other EEG patterns within each category in this nomenclature.MethodsWe defined seven spectrogram categories: “Solid Flames”, “Irregular Flames”, “Broadband-monotonous”, “Narrowband-monotonous”, “Stripes”, “Low power”, and “Artifact”. Ten electroencephalographers scored 115 spectrograms and the corresponding raw EEG samples. Gwet's agreement coefficient was used to calculate IRA.ResultsSolid Flames represented seizures or IIC patterns 69.4% of the time. Irregular Flames represented seizures or IIC patterns 38.7% of the time. Broadband-monotonous primarily corresponded with seizures or IIC (54.3%) and Narrowband-monotonous with focal or generalized slowing (43.8%). Stripes were associated with burst-suppression (37.2%) and generalized suppression (34.4%). Low Power category was associated with generalized suppression (94%). There was “near perfect” agreement for Solid Flames (κ = 94.36), Low power (κ = 92.61), and Artifact (κ = 93.72). There was “substantial agreement” for all other categories (κ = 74.65–79.49).ConclusionsThis EEG spectrogram nomenclature has high IRA among electroencephalographers.SignificanceThe nomenclature can be a useful tool for EEG screening. Future studies are needed to determine if using this nomenclature shortens time to IIC identification, and how best to use it in practice to reduce time to intervention.     

Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES)

ObjectiveTo investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants.MethodsDetailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES.ResultsNeurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2–6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60–96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood.ConclusionsNovel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia.SignificanceOur findings expand the phenotypic spectrum of CNKSR2-related ESES.     

Reduced EEG montage has a high accuracy in the post cardiac arrest setting

ObjectiveTo study if comatose cardiac arrest patients can be assessed with a reduced number of EEG electrodes.Methods110 routine EEGs from 67 consecutive patients, including both hypothermic and normothermic EEGs were retrospectively assessed by three blinded EEG-experts using two different electrode montages. A standard 19-electrode-montage was compared to the reduced version of the same EEGs, down-sampled to six electrodes (F3, T3, P3, F4, T4, P4). We used intra-rater and inter-observer statistics to assess the reliability of the reduced montage for background features and discharges.ResultsThe reduced montage had almost perfect performance for background continuity (κ 0.80–0.88), including identification of highly malignant backgrounds (burst-suppression/suppression) (κ 0.85–0.94) and benign backgrounds (continuous/nearly continuous) (κ 0.85–0.91). We found substantial performance for identifying rhythmic/periodic discharges (κ 0.79–0.86). The reduced montage had high accuracy for assessment of both highly malignant (sensitivity 91–95%, specificity 94–99%) and benign (sensitivity 89–98%, specificity 91–96%) backgrounds, and periodic/rhythmic patterns (sensitivity 79–100%, specificity 89–99%), compared to the full montage. The inter-observer variability was not increased by the reduced montage.ConclusionReduced EEG had high performance for classifying important background and discharge patterns in this post cardiac arrest cohort.SignificanceOur results support the use of reduced EEG-montage for monitoring comatose cardiac arrest patients.     

EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy

ObjectiveTo analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE).MethodsRetrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR).ResultsShort-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality.ConclusionThe presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients.SignificanceThe present findings may help to improve the challenging prognosis estimation in HE patients.     

Impaired awareness in mesial temporal lobe epilepsy: Network analysis of foramen ovale and scalp EEG

ObjectiveWe use co-registration of foramen-ovale and scalp-EEG to investigate network alterations in temporal-lobe epilepsy during focal seizures without (aura) or with impairment of awareness (SIA).MethodsOne aura and one SIA were selected from six patients. Temporal dynamic among 4 epochs, as well as the differences between aura and SIA, were analyzed through partial directed coherence and graph theory-based indices of centrality.ResultsRegarding the auras temporal evolution, fronto-parietal (FP) regions showed decreased connectivity with respect to the interictal period, in both epileptogenic (EH) and non-epileptogenic hemisphere (nEH). During SIAs, temporal dynamic showed more changes than auras: centrality of mesial temporal (mT) regions changes during all conditions, and nEH FP centrality showed the same dynamic trend of the aura (decreased centrality), until the last epoch, close to the impaired awareness, when showed increased centrality. Comparing SIA with aura, in proximity of impaired awareness, increased centrality was found in all the regions, except in nEH mT.ConclusionsOur findings suggested that the impairment of awareness is related to network alterations occurring first in neocortical regions and when awareness is still retained.SignificanceThe analysis of ‘hub’ alteration can represent a suitable biomarker for scalp EEG-based prediction of awareness impairment.     

Fixation-related potentials in naming speed: A combined EEG and eye-tracking study on children with dyslexia

ObjectiveWe combined electroencephalography (EEG) and eye-tracking recordings to examine the underlying factors elicited during the serial Rapid-Automatized Naming (RAN) task that may differentiate between children with dyslexia (DYS) and chronological age controls (CAC).MethodsThirty children with DYS and 30 CAC (M_age = 9.79 years; age range 7.6 through 12.1 years) performed a set of serial RAN tasks. We extracted fixation-related potentials (FRPs) under phonologically similar (rime-confound) or visually similar (resembling lowercase letters) and dissimilar (non-confounding and discrete uppercase letters, respectively) control tasks.ResultsResults revealed significant differences in FRP amplitudes between DYS and CAC groups under the phonologically similar and phonologically non-confounding conditions. No differences were observed in the case of the visual conditions. Moreover, regression analysis showed that the average amplitude of the extracted components significantly predicted RAN performance.ConclusionFRPs capture neural components during the serial RAN task informative of differences between DYS and CAC and establish a relationship between neurocognitive processes during serial RAN and dyslexia.SignificanceWe suggest our approach as a methodological model for the concurrent analysis of neurophysiological and eye-gaze data to decipher the role of RAN in reading.     

EEG functional connectivity contributes to outcome prediction of postanoxic coma

ObjectiveTo investigate the additional value of EEG functional connectivity features, in addition to non-coupling EEG features, for outcome prediction of comatose patients after cardiac arrest.MethodsProspective, multicenter cohort study. Coherence, phase locking value, and mutual information were calculated in 19-channel EEGs at 12 h, 24 h and 48 h after cardiac arrest. Three sets of machine learning classification models were trained and validated with functional connectivity, EEG non-coupling features, and a combination of these. Neurological outcome was assessed at six months and categorized as “good” (Cerebral Performance Category [CPC] 1–2) or “poor” (CPC 3–5).ResultsWe included 594 patients (46% good outcome). A sensitivity of 51% (95% CI: 34–56%) at 100% specificity in predicting poor outcome was achieved by the best functional connectivity-based classifier at 12 h after cardiac arrest, while the best non-coupling-based model reached a sensitivity of 32% (0–54%) at 100% specificity using data at 12 h and 48 h. Combination of both sets of features achieved a sensitivity of 73% (50–77%) at 100% specificity.ConclusionFunctional connectivity measures improve EEG based prediction models for poor outcome of postanoxic coma.SignificanceFunctional connectivity features derived from early EEG hold potential to improve outcome prediction of coma after cardiac arrest.     

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BackgroundFebrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy.Case reportA previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit.ConclusionsTo our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.     

EEG and behavioural correlates of mild sleep deprivation and vigilance

ObjectiveThe current study investigated the behavioral, cognitive, and electrophysiological impact of mild (only a few hours) and acute (one night) sleep loss via simultaneously recorded behavioural and physiological measures of vigilance.MethodsParticipants (N = 23) came into the lab for two testing days where their brain activity and vigilance were recorded and assessed. The night before the testing session, participants either slept from 12am to 9am (Normally Rested), or from 1am to 6am (Sleep Restriction).ResultsVigilance was reduced and sleepiness was increased in the Sleep Restricted vs. Normally Rested condition, and this was exacerbated over the course of performing the vigilance task. As well, sleep restriction resulted in more intense alpha bursts. Lastly, EEG spectral power differed in Sleep Restricted vs. Normally Rested conditions as sleep onset progressed, particularly for frequencies reflecting arousal (e.g., delta, alpha, beta).ConclusionsThe findings of this study suggest that only one night of mild sleep loss significantly increases sleepiness and, importantly, reduces vigilance. In addition, this sleep loss has a clear impact on the physiology of the brain in ways that reflect reduced arousal.SignificanceUnderstanding the neural correlates and cognitive processes associated with loss of sleep may lead to important advancements in identifying and preventing deleterious or potentially dangerous, sleep-related lapses in vigilance.     

Cognitive deficits and rehabilitation mechanisms in mild traumatic brain injury patients revealed by EEG connectivity markers

ObjectiveTo explore the multiple specific biomarkers and cognitive compensatory mechanisms of mild traumatic brain injury (mTBI) patients at recovery stage.MethodsThe experiment was performed in two sections. In Section I, using event-related potential, event-related oscillation and spatial phase-synchronization, we explored neural dynamics in 24 volunteered healthy controls (HC) and 38 patients at least 6 months post-mTBI (19 with epidural hematoma, EDH; 19 with subdural hematoma, SDH) during a Go/NoGo task. In Section II, according to the neuropsychological scales, patients were divided into sub-groups to assess these electroencephalography (EEG) indicators in identifying different rehabilitation outcomes of mTBI.ResultsIn Section I, mean amplitudes of NoGo-P3 and P3d were decreased in mTBI patients relative to HC, and NoGo-theta power in the non-injured hemisphere was decreased in SDH patients only. In Section II, patients with chronic neuropsychological defects exhibited more serious impairments of intra-hemispheric connectivity, whereas inter-hemispheric centro-parietal and frontal connectivity were enhanced in response to lesions.ConclusionsEEG distinguished mTBI patients from healthy controls, and estimated different rehabilitation outcomes of mTBI. The centro-parietal and frontal connectivity are the main compensatory mechanism for the recovery of mTBI patients.SignificanceEEG measurements and network connectivity can track recovery process and mechanism of mTBI.     

Contribution of altered corticospinal microstructure to gait impairment in children with cerebral palsy

ObjectiveCorticospinal tract (CST) injury may lead to motor disorders in children with Cerebral Palsy (CP). However, the precise underlying mechanisms are still ambiguous. We aimed to characterize the CST structure and function in children with CP and determine their contributions to balance and gait impairments.MethodTwenty-six children with spastic CP participated. Transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) were utilized to characterize CST structure and function. Common clinical measures were used to assess gait speed, endurance and balance, and mobility.ResultsCST structure and function were significantly altered in children with CP. Different abnormal patterns of CST structure were identified as either abnormal appearance of brain hemispheres (Group-1) or semi-normal CST appearance (Group-2). We found significant correlations between the DTI parameters of the more affected CST and gait features only in Group-1.ConclusionCST structure and function are abnormal in children with CP and these abnormalities may contribute to balance and gait impairment in some children with CP.SignificanceOur findings may lead to the development of further investigations on the mechanisms underlying gait impairment in children with CP and on decision-making for more effective rehabilitation.     

Quantitative EEG improves prediction of Sturge-Weber syndrome in infants with port-wine birthmark

ObjectivePort-wine birthmark (PWB) is a common occurrence in the newborn, and general pediatricians, dermatologists, and ophthalmologists are often called on to make an assessment of risk for Sturge-Weber syndrome (SWS) due to workforce shortages in pediatric neurologists and MRI’s low sensitivity for SWS brain involvement in infants. We therefore aimed to develop a quantitative EEG (qEEG) approach to safely screen young infants with PWB for SWS risk and optimal timing of diagnostic MRI.MethodsForty-eight infants (prior to first birthday) underwent EEG recording. Signal processing methods compared voltage between left and right sides using a previously defined pipeline and diagnostic threshold. In this test sample, we compared sensitivity/specificity of the qEEG metric against MRI performed after the first birthday. We also used likelihood ratio testing to determine whether qEEG adds incremental information beyond topographical extent of PWB, another risk marker of brain involvement.ResultsqEEG helped predict SWS risk in the first year of life (p = 0.031), with a sensitivity of 50% and a specificity of 81%. It added about 40% incremental information beyond PWB extent alone (p = 0.042).ConclusionqEEG adds information to risk prediction in infants with facial PWB.SignificanceqEEG can be used to help determine whether to obtain an MRI in the first year of life. The data collected can assist in developing a predictive model risk calculator that incorporates both PWB extent and qEEG results, which can be validated and then employed in the community.     

In pursuit of a sensitive EEG functional connectivity outcome measure for clinical trials in Alzheimer’s disease

ObjectiveIn clinical trials in Alzheimer’s Disease (AD), an improvement of impaired functional connectivity (FC) could provide biological support for the potential efficacy of the drug. Electroencephalography (EEG) analysis of the SAPHIR-trial showed a treatment induced improvement of global relative theta power but not of FC measured by the phase lag index (PLI). We compared the PLI with the amplitude envelope correlation with leakage correction (AEC-c), a presumably more sensitive FC measure.MethodsPatients with early AD underwent 12 weeks of placebo or treatment with PQ912, a glutaminylcyclase inhibitor. Eyes-closed task free EEG was measured at baseline and follow-up (PQ912 n = 47, placebo n = 56). AEC-c and PLI were measured in multiple frequency bands. Change in FC was compared between treatment groups by using two models of covariates.ResultsA significant increase in global AEC-c in the alpha frequency band was found with PQ912 treatment compared to placebo (p = 0.004, Cohen’s d = 0.58). The effect remained significant when corrected for sex, country, ApoE ε4 carriage, age, baseline value (model 1; p = 0.006) and change in relative alpha power (model 2; p = 0.004).ConclusionsFunctional connectivity in early AD, measured with AEC-c in the alpha frequency band, improved after PQ912 treatment.SignificanceAEC-c may be a robust and sensitive FC measure for detecting treatment effects.     

Dynamic functional connectivity of the EEG in relation to outcome of postanoxic coma

ObjectiveEarly EEG contains reliable information for outcome prediction of comatose patients after cardiac arrest. We introduce dynamic functional connectivity measures and estimate additional predictive values.MethodsWe performed a prospective multicenter cohort study on continuous EEG for outcome prediction of comatose patients after cardiac arrest. We calculated Link Rates (LR) and Link Durations (LD) in the α, δ, and θ band, based on similarity of instantaneous frequencies in five-minute EEG epochs, hourly, during 3 days after cardiac arrest. We studied associations of LR and LD with good (Cerebral Performance Category (CPC) 1–2) or poor outcome (CPC 3–5) with univariate analyses. With random forest classification, we established EEG-based predictive models. We used receiver operating characteristics to estimate additional values of dynamic connectivity measures for outcome prediction.ResultsOf 683 patients, 369 (54%) had poor outcome. Patients with poor outcome had significantly lower LR and longer LD, with largest differences 12 h after cardiac arrest (LR_θ 1.87 vs. 1.95 Hz and LD_α 91 vs. 82 ms). Adding these measures to a model with classical EEG features increased sensitivity for reliable prediction of poor outcome from 34% to 38% at 12 h after cardiac arrest.ConclusionPoor outcome is associated with lower dynamics of connectivity after cardiac arrest.SignificanceDynamic functional connectivity analysis may improve EEG based outcome prediction.