Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy.

BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation.

BACKGROUND: Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers. METHODS: In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women. RESULTS: Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004). CONCLUSIONS: This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.

Asymmetry of sleep electrophysiological markers in patients with focal epilepsy.

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17-61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5-4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak's multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.

Early timing of anesthesia in status epilepticus is associated with complete recovery: A 7-year retrospective two-center study.

OBJECTIVE: This study was undertaken to investigate the efficacy, tolerability, and outcome of different timing of anesthesia in adult patients with status epilepticus (SE). METHODS: Patients with anesthesia for SE from 2015 to 2021 at two Swiss academic medical centers were categorized as anesthetized as recommended third-line treatment, earlier (as first- or second-line treatment), and delayed (later as third-line treatment). Associations between timing of anesthesia and in-hospital outcomes were estimated by logistic regression. RESULTS: Of 762 patients, 246 received anesthesia; 21% were anesthetized as recommended, 55% earlier, and 24% delayed. Propofol was preferably used for earlier (86% vs. 55.5% for recommended/delayed anesthesia) and midazolam for later anesthesia (17.2% vs. 15.9% for earlier anesthesia). Earlier anesthesia was statistically significantly associated with fewer infections (17% vs. 32.7%), shorter median SE duration (.5 vs. 1.5 days), and more returns to premorbid neurologic function (52.9% vs. 35.5%). Multivariable analyses revealed decreasing odds for return to premorbid function with every additional nonanesthetic antiseizure medication given prior to anesthesia (odds ratio [OR] = .71, 95% confidence interval [CI] = .53-.94) independent of confounders. Subgroup analyses revealed decreased odds for return to premorbid function with increasing delay of anesthesia independent of the Status Epilepticus Severity Score (STESS; STESS = 1-2: OR = .45, 95% CI = .27-.74; STESS > 2: OR = .53, 95% CI = .34-.85), especially in patients without potentially fatal etiology (OR = .5, 95% CI = .35-.73) and in patients experiencing motor symptoms (OR = .67, 95% CI = .48-.93). SIGNIFICANCE: In this SE cohort, anesthetics were administered as recommended third-line therapy in only every fifth patient and earlier in every second. Increasing delay of anesthesia was associated with decreased odds for return to premorbid function, especially in patients with motor symptoms and no potentially fatal etiology.

Is the right way to go in between? : Rimegepant as needed provides preventive benefit. A comment on: monthly migraine days, tablet utilization, and quality of life associated with rimegepant-post hoc results from an open label safety study (BHV3000-201).

In the study by Johnston et al., gepants were meant to be taken to treat emergent migraine. It is tempting to speculate what the effect would be if patients were instructed to take a gepant as needed (PRN) or even prior to headache onset. While the latter sounds irrational at first glance, several studies have shown that a significant proportion of patients are quite proficient in predicting (or simply due to premonitory symptoms noting) their migraine attacks prior to the onset of actual headache. The study by Johnston et al. provides food for thought along these lines and should encourage us to further investigate flexible patient-controlled CGRP blocking as a third, intermediate and potentially cost-effective avenue between acute/rescue treatment and prevention/prophylaxis.

[New developments in headache management in 2022]. / Nouveautés dans la prise en charge des céphalées.

Headaches are one of the most common causes of consultation in primary care. Due to their polymorphic character and sometimes severe etiologies, it is very important to properly classify these symptoms and to look for possible associated signs of severity. It is with this objective that the international classification of headache delivered its 3rd version in 2018 with the ICHD-3. In addition, revised and validated severity criteria were also published in 2018 under the name SNNOOP10. At the same time, the concept of green flags which could allow to diagnose a primary headache without further investigations has emerged. In terms of treatment, the development of CGRP neuropeptide antagonists has allowed a major advance in the treatment of the severe forms of migraine. Finally, integrative medicine is taking on a central role.

Les céphalées sont l'un des motifs de consultation les plus courants en médecine de premier recours. En raison de leur caractère polymorphe et des étiologies potentiellement graves, il est essentiel de bien les classifier et de rechercher les signes de sévérité associés. C'est dans cet objectif que la classification internationale des céphalées a livré sa troisième version en 2018 (ICHD-3). Des critères de sévérité révisés et validés ont également été publiés en 2018 sous le nom de SNNOOP10. En parallèle, le concept de drapeaux verts, qui permettrait de retenir un diagnostic de céphalées primaires sans autres examens, a émergé. En termes de traitement, le développement d'antagonistes du neuropeptide CGRP (Calcitonin Gene-Related Peptide) a permis une avancée majeure dans le traitement des formes de migraine sévères. La médecine intégrative y prend par ailleurs une place centrale.

Acute symptomatic seizures and hippocampal sclerosis: the major contributor for post-stroke epilepsy?

OBJECTIVE: Hippocampal sclerosis (HS) is a prominent biomarker of epilepsy. If acquired later in life, it usually occurs in the context of degenerative or acute inflammatory-infectious disease. Conversely, acute symptomatic seizures (ASS) are considered a risk factor for developing post-stroke epilepsy, but other factors remain unrecognized. Here, we hypothesize that silent hippocampal injury contributes to the development of post-stroke epilepsy. METHODS: We performed a retrospective observational study of patients hospitalized between 1/2007 and 12/2018 with an acute stroke in the Stroke Center of the Geneva University Hospital. Patients were included if they had a documented normal hippocampal complex at onset and a control MRI at ≥ 2 year interval without new lesion in the meantime. RESULTS: 162 patients fulfilled our inclusion criteria. ASS during the first week (p < 0.0001) and epileptiform abnormalities in electroencephalography (EEG; p = 0.02) were more frequently associated with the development of epilepsy. Hemorrhagic stroke was strongly associated to both ASS and future focal epilepsy (p = 0.00097). Three patients (1.8%) developed hippocampal sclerosis ipsilateral to the cerebrovascular event between 2 and 5 years, all with ASS and hemorrhagic stroke. INTERPRETATION: ASS and epileptiform EEG abnormalities are strong predictors of post-stroke epilepsy. HS develops in a minority of patients after hemorrhagic lesions, leading to focal epilepsy. Prospective studies are required, including follow-up with EEG and if characterized by epileptiform discharges, with MRI, to determine the true frequency of HS and to better understand predictors of post-stroke epilepsy (AAS, stroke type, and HS), and their impact on stroke recovery.

The neural correlates of intermanual transfer.

Intermanual transfer of motor learning is a form of learning generalization that leads to behavioral advantages in various tasks of daily life. It might also be useful for rehabilitation of patients with unilateral motor deficits. Little is known about neural structures and cognitive processes that mediate intermanual transfer. Previous studies have suggested a role for primary motor cortex (M1) and the supplementary motor area (SMA). Here, we investigated the functional neuroanatomy of intermanual transfer with a special emphasis on functional connectivity within the motor network and between motor regions and attentional networks, including the fronto-parietal executive control network and visual attention networks. We designed a finger tapping task, in which young, heathy subjects trained the non-dominant left hand in the MRI scanner. Behaviorally, transfer of sequence learning was observed in most cases, independently of the trained hand's performance. Pre- and post-training functional connectivity patterns of cortical motor seeds were investigated using generalized psychophysiological interaction analyses. Transfer was correlated with the strength of connectivity between the left premotor cortex and structures within the dorsal attention network (superior parietal cortex, left middle temporal gyrus) and executive control network (right prefrontal regions) during pre-training, relative to post-training. Changes in connectivity within the motor network, and more particularly between trained and untrained M1, as well as between the SMA and untrained M1, correlated with transfer after training. Together, these results suggest that the interplay between attentional, executive and motor networks may support processes leading to transfer, whereas, following training, transfer translates into increased connectivity within the motor network.

Slow oscillations open susceptible time windows for epileptic discharges.

OBJECTIVE: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression. METHODS: We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities. RESULTS: Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges. SIGNIFICANCE: Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.

[Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations]. / Smarter Medicine in Diagnose und Behandlung von Kopfschmerzen.

Smarter Medicine in Headache Care - presentation and discussion of 5 recommendations Abstract. An unequivocal headache diagnosis cannot always be made. The lack of diagnostic tests able to prove primary headaches often prompts physicians to perform unnecessary examinations to reduce their uncertainty. When setting out the therapeutic strategy, again, insecurity often leads to mendable choices. In this Delphi study, members of the therapy commission of the Swiss Headache Society collected, rated, and re-rated doubtful and questionable procedures. Five recommendations that resulted from this survey are presented and reviewed in this article. The recommendations are: (A) no repeated cerebral imaging in headaches with unchanged phenotype; (B) no computed tomography in the work-up of non-acute headaches; (C) no tooth extraction to treat persistent idiopathic facial pain, (D) no migraine surgery; (E) no removal of amalgam fillings to treat headache disorders.

Periinfarct rewiring supports recovery after primary motor cortex stroke.

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.

Integrating regional perfusion CT information to improve prediction of infarction after stroke.

Physiological evidence suggests that neighboring brain regions have similar perfusion characteristics (vascular supply, collateral blood flow). It is largely unknown whether integrating perfusion CT (pCT) information from the area surrounding a given voxel (i.e. the receptive field (RF)) improves the prediction of infarction of this voxel. Based on general linear regression models (GLMs) and using acute pCT-derived maps, we compared the added value of cuboid RF to predict the final infarct. To this aim, we included 144 stroke patients with acute pCT and follow-up MRI, used to delineate the final infarct. Overall, the performance of GLMs to predict the final infarct improved when using RF for all pCT maps (cerebral blood flow, cerebral blood volume, mean transit time and time-to-maximum of the tissue residual function (Tmax)). The highest performance was obtained with Tmax (glm(Tmax); AUC = 0.89 ± 0.03 with RF vs. 0.78 ± 0.02 without RF; p < 0.001) and with a model combining all perfusion parameters (glm(multi); AUC 0.89 ± 0.02 with RF vs. 0.79 ± 0.02 without RF; p < 0.001). These results suggest that prediction of infarction improves by integrating perfusion information from adjacent tissue. This approach may be applied in future studies to better identify ischemic core and penumbra thresholds and improve patient selection for acute stroke treatment.

Spontaneous Network Coupling Enables Efficient Task Performance without Local Task-Induced Activations.

Neurobehavioral studies in humans have long concentrated on changes in local activity levels during repetitive executions of a task. Spontaneous neural coupling within extended networks has latterly been found to also influence performance. Here, we intend to uncover the underlying mechanisms, the relative importance, and the interaction between spontaneous coupling and task-induced activations. To do so, we recorded two groups of healthy participants (male and female) during rest and while they performed either a visual perception or a motor sequence task. We demonstrate that, for both tasks, stronger activations during the task as well as greater network coupling through spontaneous α rhythms at rest predict performance. However, high performers present an absence of classical task-induced activations and, instead, stronger spontaneous network coupling. Activations were thus a compensation mechanism needed only in subjects with lower spontaneous network interactions. This challenges classical models of neural processing and calls for new strategies in attempts to train and enhance performance.SIGNIFICANCE STATEMENT Our findings challenge the widely accepted notion that task-induced activations are of paramount importance for behavior. This will have an important impact on interpretations of human neurobehavioral research. They further link the widely used techniques of quantifying network communication in the brain with classical neuroscience methods and demonstrate possible ways of how network communication influences human behavior. Traditional training methods attempt to enhance neural activations through task repetitions. Our findings suggest a more efficient neural target for learning: enhancing spontaneous neural interactions. This will be of major interest for a large variety of scientific fields with very broad applications in schools, work, and others.

The rough sound of salience enhances aversion through neural synchronisation.

Being able to produce sounds that capture attention and elicit rapid reactions is the prime goal of communication. One strategy, exploited by alarm signals, consists in emitting fast but perceptible amplitude modulations in the roughness range (30-150 Hz). Here, we investigate the perceptual and neural mechanisms underlying aversion to such temporally salient sounds. By measuring subjective aversion to repetitive acoustic transients, we identify a nonlinear pattern of aversion restricted to the roughness range. Using human intracranial recordings, we show that rough sounds do not merely affect local auditory processes but instead synchronise large-scale, supramodal, salience-related networks in a steady-state, sustained manner. Rough sounds synchronise activity throughout superior temporal regions, subcortical and cortical limbic areas, and the frontal cortex, a network classically involved in aversion processing. This pattern correlates with subjective aversion in all these regions, consistent with the hypothesis that roughness enhances auditory aversion through spreading of neural synchronisation.

Discriminability of numerosity-evoked fMRI activity patterns in human intra-parietal cortex reflects behavioral numerical acuity.

Areas of the primate intraparietal cortex have been identified as an important substrate of numerical cognition. In human fMRI studies, activity patterns in these and other areas have allowed researchers to read out the numerosity a subject is viewing, but the relation of such decodable information with behavioral numerical proficiency remains unknown. Here, we estimated the precision of behavioral numerosity discrimination (internal Weber fraction) in twelve adult subjects based on psychophysical testing in a delayed numerosity comparison task outside the scanner. FMRI data were then recorded during a similar task, to obtain the accuracy with which the same sample numerosities could be read out from evoked brain activity patterns, as a measure of the precision of the neuronal representation. Sample numerosities were decodable in both early visual and intra-parietal cortex with approximately equal accuracy on average. In parietal cortex, smaller numerosities were better discriminated than larger numerosities of the same ratio, paralleling smaller behavioral Weber fractions for smaller numerosities. Furthermore, in parietal but not early visual cortex, fMRI decoding performance was correlated with behavioral number discrimination acuity across subjects (subjects with a more precise behavioral Weber fraction measured prior to scanning showed greater discriminability of fMRI activity patterns in intraparietal cortex, and more specifically, the right LIP region). These results suggest a crucial role for intra-parietal cortex in supporting a numerical representation which is explicitly read out for numerical decisions and behavior.

Alpha Oscillations Reduce Temporal Long-Range Dependence in Spontaneous Human Brain Activity.

Ongoing neural dynamics comprise both frequency-specific oscillations and broadband-features, such as long-range dependence (LRD). Despite both being behaviorally relevant, little is known about their potential interactions. In humans, 8-12 Hz α oscillations constitute the strongest deviation from 1/f power-law scaling, the signature of LRD. We postulated that α oscillations, believed to exert active inhibitory gating, downmodulate the temporal width of LRD in slower ongoing brain activity. In two independent "resting-state" datasets (electroencephalography surface recordings and magnetoencephalography source reconstructions), both across space and dynamically over time, power of α activity covaried with the power slope <5 Hz (i.e., greater α activity shortened LRD). Causality of α activity dynamics was implied by its temporal precedence over changes of slope. A model where power-law fluctuations of the α envelope inhibit baseline activity closely replicated our results. Thus, α oscillations may provide an active control mechanism to adaptively regulate LRD of brain activity at slow temporal scales, thereby shaping internal states and cognitive processes.SIGNIFICANCE STATEMENT The two prominent features of ongoing brain activity are oscillations and temporal long-range dependence. Both shape behavioral performance, but little is known about their interaction. Here, we demonstrate such an interaction in EEG and MEG recordings of task-free human brain activity. Specifically, we show that spontaneous dynamics in alpha activity explain ensuing variations of dependence in the low and ultra-low-frequency range. In modeling, two features of alpha oscillations are critical to account for the observed effects on long-range dependence, scale-free properties of alpha oscillations themselves, and a modulation of baseline levels, presumably inhibitory. Both these properties have been observed empirically, and our study hence establishes alpha oscillations as a regulatory mechanism governing long-range dependence or "memory" in slow ongoing brain activity.