EEG–fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG–fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG–fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG–fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG–fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures

Bilateral 5 Hz transcranial alternating current stimulation on fronto-temporal areas modulates resting-state EEG

Rhythmic non-invasive brain stimulations are promising tools to modulate brain activity by entraining neural oscillations in specific cortical networks. The aim of the study was to assess the possibility to influence the neural circuits of the wake-sleep transition in awake subjects via a bilateral transcranial alternating current stimulation at 5 Hz (theta-tACS) on fronto-temporal areas. 25 healthy volunteers participated in two within-subject sessions (theta-tACS and sham), one week apart and in counterbalanced order. We assessed the stimulation effects on cortical EEG activity (28 derivations) and self-reported sleepiness (Karolinska Sleepiness Scale). theta-tACS induced significant increases of the theta activity in temporo-parieto-occipital areas and centro-frontal increases in the alpha activity compared to sham but failed to induce any online effect on sleepiness. Since the total energy delivered in the sham condition was much less than in the active theta-tACS, the current data are unable to isolate the specific effect of entrained theta oscillatory activity per se on sleepiness scores. On this basis, we concluded that theta-tACS modulated theta and alpha EEG activity with a topography consistent with high sleep pressure conditions. However, no causal relation can be traced on the basis of the current results between these rhythms and changes on sleepines

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

The spatiotemporal pattern of the human electroencephalogram at sleep onset after a period of prolonged wakefulness

During the sleep onset (SO) process, the human electroencephalogram (EEG) is characterized by an orchestrated pattern of spatiotemporal changes. Sleep deprivation (SD) strongly affects both wake and sleep EEG, but a description of the topographical EEG power spectra and oscillatory activity during the wake-sleep transition after a period of prolonged wakefulness is still missing. The increased homeostatic sleep pressure should induce an earlier onset of sleep-related EEG oscillations. The aim of the present study was to assess the spatiotemporal EEG pattern at SO following SD. A dataset of a previous study was analyzed. We assessed the spatiotemporal EEG changes (19 cortical derivations) during the SO (5 min before vs. 5 min after the first epoch of Stage 2) of a recovery night after 40 h of SD in 39 healthy subjects, analyzing the EEG power spectra (fast Fourier transform) and the oscillatory activity [better oscillation (BOSC) detection method]. The spatiotemporal pattern of the EEG power spectra mostly confirmed the changes previously observed during the wake-sleep transition at baseline. The comparison between baseline and recovery showed a wide increase of the post- vs. pre-SO ratio during the recovery night in the frequency bins 10 Hz. We found a predominant alpha oscillatory rhythm in the pre-SO period, while after SO the theta oscillatory activity was prevalent. The oscillatory peaks showed a generalized increase in all frequency bands from delta to sigma with different predominance, while beta activity increased only in the fronto-central midline derivations. Overall, the analysis of the EEG power replicated the topographical pattern observed during a baseline night of sleep but with a stronger intensity of the SO-induced changes in the frequencies 10 Hz, and the detection of the rhythmic activity showed the rise of several oscillations at SO after SD that was not observed during the wake-sleep transition at baseline (e.g., alpha and frontal theta in correspondence of their frequency peaks). Beyond confirming the local nature of the EEG pattern at SO, our results show that SD has an impact on the spatiotemporal modulation of cortical activity during the falling-asleep process, inducing the earlier emergence of sleep-related EEG oscillations

The Involvement of Noradrenaline in Rapid Eye Movement Sleep Mentation

Noradrenaline, one of the main brain monoamines, has powerful central influences on forebrain neurobiological processes which support the mental activities occurring during the sleep–waking cycle. Noradrenergic neurons are activated during waking, decrease their firing rate during slow wave sleep, and become silent during rapid eye movement (REM) sleep. Although a low level of noradrenaline is still maintained during REM sleep because of diffuse extrasynaptic release without rapid withdrawal, the decrease observed during REM sleep contributes to the mentation disturbances that occur during dreaming, which principally resemble symptoms of schizophrenia but seemingly also of attention deficit hyperactivity disorder

Towards dynamical network biomarkers in neuromodulation of episodic migraine

Computational methods have complemented experimental and clinical neursciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.Comment: 13 pages, 5 figure

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

An unaware agenda: interictal consciousness impairments in epileptic patients.

Consciousness impairments have been described as a cornerstone of epilepsy. Generalized seizures are usually characterized by a complete loss of consciousness, whereas focal seizures have more variable degrees of responsiveness. In addition to these impairments that occur during ictal episodes, alterations of consciousness have also been repeatedly observed between seizures (i.e. during interictal periods). In this opinion article, we review evidence supporting the novel hypothesis that epilepsy produces consciousness impairments which remain present interictally. Then, we discuss therapies aimed to reduce seizure frequency, which may modulate consciousness between epileptic seizures. We conclude with a consideration of relevant pathophysiological mechanisms. In particular, the thalamocortical network seems to be involved in both seizure generation and interictal consciousness impairments, which could inaugurate a promising translational agenda for epilepsy studies

Cortical glucose metabolism correlates negatively with delta-slowing and spike-frequency in epilepsy associated with tuberous sclerosis

The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5–16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike-frequency measured in the given electrode site. The regression slopes as well as R -square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was −0.0025 (95% CI: −0.0045 to −0.0004; P = 0.02 based on one-sample t -test) and that for spike frequency was −0.023 (95% CI: −0.042 to −0.0038; P = 0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta, and gamma activities) were not significantly different from zero. The mean R -square value was 0.39. These results suggest that increased delta-slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow-wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61224/1/20461_ftp.pd