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.

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.

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.

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.

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 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.

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.

Ongoing dynamics in large-scale functional connectivity predict perception.

Most brain activity occurs in an ongoing manner not directly locked to external events or stimuli. Regional ongoing activity fluctuates in unison with some brain regions but not others, and the degree of long-range coupling is called functional connectivity, often measured with correlation. Strength and spatial distributions of functional connectivity dynamically change in an ongoing manner over seconds to minutes, even when the external environment is held constant. Direct evidence for any behavioral relevance of these continuous large-scale dynamics has been limited. Here, we investigated whether ongoing changes in baseline functional connectivity correlate with perception. In a continuous auditory detection task, participants perceived the target sound in roughly one-half of the trials. Very long (22-40 s) interstimulus intervals permitted investigation of baseline connectivity unaffected by preceding evoked responses. Using multivariate classification, we observed that functional connectivity before the target predicted whether it was heard or missed. Using graph theoretical measures, we characterized the difference in functional connectivity between states that lead to hits vs. misses. Before misses compared with hits and task-free rest, connectivity showed reduced modularity, a measure of integrity of modular network structure. This effect was strongest in the default mode and visual networks and caused by both reduced within-network connectivity and enhanced across-network connections before misses. The relation of behavior to prestimulus connectivity was dissociable from that of prestimulus activity amplitudes. In conclusion, moment to moment dynamic changes in baseline functional connectivity may shape subsequent behavioral performance. A highly modular network structure seems beneficial to perceptual efficiency.

An exploratory cohort study of sensory extinction in acute stroke: prevalence, risk factors, and time course.

Most studies on sensory extinction have focused on selected patients with subacute and chronic right hemisphere lesions. In studies conducted on acute stroke patients, risk factors and time course were not evaluated. Our aim was to determine the prevalence, risk factors, and time course of sensory extinction in the acute stroke setting. Consecutive patients with acute stroke were tested for tactile, visual, auditory, and auditory-tactile cross-modal extinction, as well as for peripersonal visuospatial neglect (PVN). Tests were repeated at 2, 7, 15, 30, and 90 days after initial examination. A multivariable logistic regression analysis was performed to test the association between sensory extinction and demographic and clinical risk factors. Seventy-three patients (38.4% women) were recruited: 64 with ischemic stroke and nine with haemorrhagic stroke. Mean age was 62.3 years (95% CI 58.8-65.7), mean NIHSS score was 1.6 (95% CI 1.2-2.1), and mean time to first examination was 4.1 days (95% CI 3.5-4.8). The overall prevalence of all subtypes of sensory extinction was 13.7% (95% CI 6.8-23.8). Tactile extinction was the most frequent subtype with a prevalence of 8.2% (95% CI 3.1-17.0). No extinction was found beyond 15 days after the first examination. After adjustment for age, sex, lesion side, type of stroke, time to first examination and stroke severity, a lesion volume ≥2 mL (adjusted OR = 38.88, p = 0.04), and presence of PVN (adjusted OR = 24.27, p = 0.04) were independent predictors of sensory extinction. The insula, the putamen, and the pallidum were the brain regions most frequently involved in patients with sensory extinction. Extinction is a rare and transient phenomenon in patients with minor stroke. The presence of PVN and lesion volume ≥2 mL are independent predictors of sensory extinction in acute stroke.

Cingulo-opercular network activity maintains alertness.

Previous investigations of alertness have confounded it with selective attention because targets were highly predictable. To truly isolate alertness we devised a sparse event-related design with many different randomly appearing and interleaved auditory and visual targets, thereby rendering prediction inefficient. Using functional magnetic resonance imaging, we then analyzed the influence of local brain activity variations prior to task appearance on reaction times, thus avoiding signal contributions from stimulus-driven attention. Higher pre-stimulus activity in a cingulo-opercular network, and the default mode network, resulted in faster response speed but only the former network showed task-positive responses. Conversely, dorsal attention network pre-stimulus activity was overall irrelevant and on auditory trials even detrimental to performance. Thus, in a paradigm where no information predicted timing, modality or properties of a subsequent stimulus, our results dissociate alertness, both anatomically and functionally, from attention and establish the central role of the cingulo-opercular network for sustaining alertness.

[Migraine: from generic recommendations to practical taking in charge]. / Migraine: des recommandations générales a la prise en charge pratique.

Although with an 11% prevalence migraine is a major public health problem, many patients are not satisfied with its handling by medical professionals. Migraine is a clinical diagnosis based on typically lateralized throbbing headache with nausea and/or photo- and phonophobia. It can in some be preceded by an aura with transient focal neurological symptoms. There are several "red flags" of clinical presentation, however, that should induce further examination with brain imaging studies. Treatment is based on identifying and avoiding provoking factors, on treating attacks with rescue medication (simple pain killers or triptans), on identifying conditions for a prophylactic treatment by one of several possible substance classes, and most importantly, on establishing a solid therapeutic relationship with the patient.

Temporal tuning properties along the human ventral visual stream.

Both our environment and our behavior contain many spatiotemporal regularities. Preferential and differential tuning of neural populations to these regularities can be demonstrated by assessing rate dependence of neural responses evoked during continuous periodic stimulation. Here, we used functional magnetic resonance imaging to measure regional variations of temporal sensitivity along the human ventral visual stream. By alternating one face and one house stimulus, we combined sufficient low-level signal modulation with changes in semantic meaning and could therefore drive all tiers of visual cortex strongly enough to assess rate dependence. We found several dissociations between early visual cortex and middle- and higher-tier regions. First, there was a progressive slowing down of stimulation rates yielding peak responses along the ventral visual stream. This finding shows the width of temporal integration windows to increase at higher hierarchical levels. Next, for fixed rates, early but not higher visual cortex responses additionally depended on the length of stimulus exposure, which may indicate increased persistence of responses to short stimuli at higher hierarchical levels. Finally, attention, which was recruited by an incidental task, interacted with stimulation rate and shifted tuning peaks toward lower frequencies. Together, these findings quantify neural response properties that are likely to be operational during natural vision and that provide putative neurofunctional substrates of mechanisms that are relevant in several psychophysical phenomena as masking and the attentional blink. Moreover, they illustrate temporal constraints for translating the deployment of attention into enhanced neural responses and thereby account for lower limits of attentional dwell time.

α-band phase synchrony is related to activity in the fronto-parietal adaptive control network.

Neural oscillations in the alpha band (8-12 Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase synchronization of alpha oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the alpha band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of alpha band phase synchrony. We adapted the phase-locking value to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent EEG and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper alpha band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well known fronto-parietal (FP) network. Spectral correlations with this network's activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale alpha phase synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper alpha band synchrony is well suited to support these functions. Complementing our previous findings that related alpha oscillation power to neural structures serving tonic control, the current findings link alpha phase synchrony to neural structures underpinning phasic control of alertness and task requirements.

Functional interactions between intrinsic brain activity and behavior.

The brain continuously maintains a remarkably high level of intrinsic activity. This activity is non-stationary and its dynamics reveal highly structured patterns across several spatial scales, from fine-grained functional architecture in sensory cortices to large-scale networks. The mechanistic function of this activity is only poorly understood. The central goal of the current review is to provide an integrated summary of recent studies on structure, dynamics and behavioral consequences of spontaneous brain activity. In light of these empirical observations we propose that the structure of ongoing activity and its itinerant nature can be understood as an indispensible memory system modeling the statistical structure of the world. We review the dynamic properties of ongoing activity, and how they are malleable over short to long temporal scales that permit adapting over a range of short- to long-term cognitive challenges. We conclude by reviewing how the functional significance of ongoing activity manifests in its impact on human action, perception, and higher cognitive function.

Disconnecting cognition.

PURPOSE OF REVIEW: The aim is to assess whether the recent surge in brain 'connectivity' studies has improved our understanding of neurological deficits and in particular so-called disconnection syndromes. RECENT FINDINGS: Across a large variety of brain diseases, functional connectivity measures obtained from 'resting state' studies show alterations in distributed neural networks that may be of explanatory value for disease severity. In parallel, studies of structural connectivity reveal how damage to identified fiber tracts can yield specific clinical symptoms. These methods are not only permitting testing of the disconnection mechanism in the few syndromes where it has classically been suspected, but also starting to propose disconnection accounts for other syndromes that have not been conceptualized this way before. Finally, both structural and functional connectivity studies contribute to improve the mechanistic understanding of cognitive deficits in disseminated white matter disease. SUMMARY: In many respects, studies of structural and functional connectivity using MRI are providing critical novel empirical evidence for--and also against--disconnection as the relevant pathomechanism in neurological syndromes. At the same time, the observation of altered long-range correlation of activity in a wide variety of brain diseases may also be overinterpreted as disconnection, which dilutes an originally rather specific understanding of this concept.