Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.DOI: http://dx.doi.org/10.7554/eLife.22001.001

EEG-correlated fMRI can provide localisation information on the generators of epileptiform discharges in patients with focal epilepsy. To increase the technique's clinical potential, it is important to consider ways of optimising the yield of each experiment while minimizing the risk of false positive activation. Head motion can lead to severe image degradation and result in false positive activation, and is usually worse in patients than in healthy subjects. We performed General Linear Model (GLM) fMRI data analysis on simultaneous EEG-fMRI data acquired in 34 cases with focal epilepsy. Signal changes associated with large inter-scan motion events (head jerks) were modelled using modified design matrices that include 'scan nulling' regressors. We evaluated the efficacy of this approach by mapping the proportion of the brain for which F-tests across the additional regressors were significant. In 95% of cases, there was a significant effect of motion in 50% of the brain or greater; for the scan nulling effect, the proportion was 36%; this effect was predominantly in the neocortex. We conclude that careful consideration of the motionrelated effects in fMRI studies of patients with epilepsy is essential and that the proposed approach can be effective. Lemieux et al.Large motion in fMRI 3

ObjectiveSurgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome.MethodsTwenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year.ResultsTwelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery.InterpretationComparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome. ANN NEUROL 2011

There is a growing body of evidence pointing toward large-scale networks underlying the core phenomena in epilepsy, from seizure generation to cognitive dysfunction or response to treatment. The investigation of networks in epilepsy has become a key concept to unlock a deeper understanding of the disease. Functional imaging can provide valuable information to characterize network dysfunction; in particular resting state fMRI (RS-fMRI), which is increasingly being applied to study brain networks in a number of diseases. In patients with epilepsy, network connectivity derived from RS-fMRI has found connectivity abnormalities in a number of networks; these include the epileptogenic, cognitive and sensory processing networks. However, in majority of these studies, the effect of epileptic transients in the connectivity of networks has been neglected. EEG–fMRI has frequently shown networks related to epileptic transients that in many cases are concordant with the abnormalities shown in RS studies. This points toward a relevant role of epileptic transients in the network abnormalities detected in RS-fMRI studies. In this review, we summarize the network abnormalities reported by these two techniques side by side, provide evidence of their overlapping findings, and discuss their significance in the context of the methodology of each technique. A number of clinically relevant factors that have been associated with connectivity changes are in turn associated with changes in the frequency of epileptic transients. These factors include different aspects of epilepsy ranging from treatment effects, cognitive processes, or transition between different alertness states (i.e., awake–sleep transition). For RS-fMRI to become a more effective tool to investigate clinically relevant aspects of epilepsy it is necessary to understand connectivity changes associated with epileptic transients, those associated with other clinically relevant factors and the interaction between them, which represents a gap in the current literature. We propose a framework for the investigation of network connectivity in patients with epilepsy that can integrate epileptic processes that occur across different time scales such as epileptic transients and disease duration and the implications of this approach are discussed.