Alessandra Del Felice

The sleep-deprived brain in normals and patients with juvenile myoclonic epilepsy: A perturbational approach to measuring cortical reactivity

Simultaneous electroencephalography-transcranial magnetic stimulation (EEG-TMS) investigates cortical reactivity to external perturbations. TMS evoked potentials (TEPs) have been described in normals during sleep and wake but not after sleep deprivation or in pathologically enhanced excitability, i.e., epilepsy. The aim of our study was to identify TEPs and their modifications via EEG-TMS co-registration in healthy controls and patients with juvenile myoclonic epilepsy (JME) during wake, sleep deprivation and sleep conditions. Focal TMS was administered to the primary motor cortex in 12 healthy controls and 10 patients with JME. At least 150 TMS were delivered randomly every 8-15s during wake, sleep deprivation and sleep conditions. EEG was simultaneously acquired from 32 scalp electrodes. A significant increase in late peak amplitudes (P100 and N190) was observed in all subjects during the sleep-deprived condition, with a marked anterior increase and overall higher amplitude potentials in the JME patients. We demonstrated an overall higher cortical excitability in the JME patients, particularly over the anterior cortex after sleep deprivation and rebound sleep. This phenomenon could be related to the cortico-thalamic circuit dysfunctions believed to cause myoclonic epilepsy and a higher susceptibility of the frontal and prefrontal areas to the effects of sleep deprivation.

Combining ESI, ASL and PET for quantitative assessment of drug-resistant focal epilepsy

When localization of the epileptic focus is uncertain, the epileptic activity generator may be more accurately identified with non-invasive imaging techniques which could also serve to guide stereo-electroencephalography (sEEG) electrode implantation. The aim of this study was to assess the diagnostic value of perfusion magnetic resonance imaging with arterial spin labeling (ASL) in the identification of the epileptogenic zone, as compared to the more invasive positron-emission tomography (PET) and other established investigation methods for source imaging of electroencephalography (EEG) data. In 6 patients with drug-resistant focal epilepsy, standard video-EEG was performed to identify clinical seizure semeiology, and high-density EEG, ASL and FDG-PET to non-invasively localize the epileptic focus. A standardized source imaging procedure, low-resolution brain electromagnetic tomography constrained to the individual matter, was applied to the averaged spikes of high-density EEG. Quantification of current density, cerebral blood flow, and standardized uptake value were compared over the same anatomical areas. In most of the patients, source in the interictal phase was associated with an area of hypoperfusion and hypometabolism. Conversely, in the patients presenting with early post-ictal discharges, the brain area identified by electrical source imaging (ESI) as the generating zone appeared to be hyperperfused. In 2 patients in whom the focus remained uncertain, the postoperative follow-up showed the disappearance of epileptic activity. As an innovative and more comprehensive approach to the study of epilepsy, the combined use of ESI, perfusion MRI, and PET may play an increasingly important role in the non-invasive evaluation of patients with refractory focal epilepsy.

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool

BACKGROUND Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. OBJECTIVE/HYPOTHESIS To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. METHODS Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). RESULTS An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. CONCLUSIONS Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE.

Patient-Specific Detection of Cerebral Blood Flow Alterations as Assessed by Arterial Spin Labeling in Drug-Resistant Epileptic Patients

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients.

Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence

BACKGROUND Addiction is associated with dorso-lateral prefrontal cortex (DLPFC) dysfunction and altered brain-oscillations. High frequency repetitive transcranial magnetic stimulation (HFrTMS) over DLPFC reportedly reduces drug craving. Its effects on neuropsychological, behavioural and neurophysiological are unclear. METHODS We assessed psychological, behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification. Participants were randomized to active HFrTMS (10 Hz, 100% motor threshold) or sham. Immediately before the first and after the last session, 32-channels EEG was recorded and alcohol craving Visual Analogue Scale, Symptom Check List-90-R, Numeric Stroop task and Go/No-go task administered. Tests were repeated at 1-month follow-up. RESULTS 17 subjects (mean age 44.7 years, 4 F) were assessed. Active rTMS subjects performed better at Stroop test at end of treatment (p=0.036) and follow up (p=0.004) and at Go-NoGo at end of treatment (p=0.05) and follow up (p=0.015). Depressive symptoms decreased at end of active treatment (p=0.036). Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham (p=0.026). No significant modifications over time or group emerged for craving and number of drinks at follow up. CONCLUSION 4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms. An overall reduction of faster EEG frequencies was observed. Nonetheless, this schedule is ineffective in reducing craving and alcohol intake.

Time-frequency analysis of short-lasting modulation of EEG induced by TMS during wake, sleep deprivation and sleep

The occurrence of dynamic changes in spontaneous electroencephalogram (EEG) rhythms in the awake state or sleep is highly variable. These rhythms can be externally modulated during transcranial magnetic stimulation (TMS) with a perturbation method to trigger oscillatory brain activity. EEG-TMS co-registration was performed during standard wake, during wake after sleep deprivation and in sleep in six healthy subjects. Dynamic changes in the regional neural oscillatory activity of the cortical areas were characterized using time-frequency analysis based on the wavelet method, and the modulation of induced oscillations were related to different vigilance states. A reciprocal synchronizing/desynchronizing effect on slow and fast oscillatory activity was observed in response to focal TMS after sleep deprivation and sleep. We observed a sleep-related slight desynchronization of alpha mainly over the frontal areas, and a widespread increase in theta synchronization. These findings could be interpreted as proof of the interference external brain stimulation can exert on the cortex, and how this could be modulated by the vigilance state. Potential clinical applications may include evaluation of hyperexcitable states such as epilepsy or disturbed states of consciousness such as minimal consciousness.

Transient epileptic amnesia mistaken for mild cognitive impairment? A high-density EEG study

Mild cognitive impairment (MCI) converts to Alzheimers disease within a few years of diagnosis in up to 80% of patients. The identification among such a population of a rare form of epilepsy (transient epileptic amnesia [TEA]), characterized by mixed anterograde and retrograde amnesia with apparent preservation of other cognitive functions, excessively rapid decay of newly acquired memories, and loss of memories for salient personal events of the remote past, strongly affects prognosis and medical treatment. Our aim was to define the clinical utility of routine high-density electroencephalography (EEG) in patients with MCI for the detection of epilepsy, especially TEA. Using high-density EEG (256 channels), we were able to single out 3 cases of TEA previously misdiagnosed as MCI in this cohort of 76 consecutive patients with MCI diagnosed at our center. Antiepileptic treatment effectively stopped the acute episodes of memory loss. To our knowledge, this is the first report of an incidence of 4% of TEA recorded in such a cohort.

EEG-fMRI coregistration in non-ketotic hyperglycemic occipital seizures

We report the first case, to our knowledge, of non-ketotic hyperglycemic (NKH) related occipital seizures studied by continuous EEG-fMRI in an undiagnosed diabetic patient. Ictal EEG showed left posterior spikes and sharp-waves. Seizures subsided after insulin therapy was started. Continuous EEG-fMRI was performed and BOLD activation was identified in the left Brodmanns area 18 (visual association area). Activation of an epileptic focus related with the patients metabolic disturbance can be postulated.

Electrical Source Imaging of Sleep Spindles

To identify and compare cortical source generators of slow and fast sleep spindles in healthy subjects, electroencephalographic (EEG) signals were obtained from 256 channels, and sources on neuroanatomical Montreal Neurological Institute (MNI) space estimated with low-resolution brain electromagnetic tomography analysis (LORETA). Spindle activity was recorded in 18 healthy volunteers during daytime napping. Because of lack of sleep or excessive artifacts, data from 13 subjects were analyzed off-line. Spindles were visually scored, marked, and bandpass filtered (slow 10-12 Hz or fast 12-14 Hz). EEG was segmented on the marker, and segments separately averaged. LORETA projected cortical sources on the MNI brain. Maximal intra- and inter-individual intensities were compared using the Wilcoxon test (P< .05) and cortical sources distribution compared using a χ2 test. Two to three slow spindles generators were consistently identified in frontal lobes, with additional sources in parietal and limbic lobes in half cases. Fast spindles had multiple temporo-parietal sources, with an inconstant frontal source. Inter-individual (P = 0.44), and intra-individual (P = 0.09 slow and P = 0.10 fast spindles) source intensities were comparable. Slow spindles sources were preferentially concentrated over frontal cortices in comparison with fast spindles (P = 0.0009). Our results demonstrate multiple, synchronous, and equipotent spindles cortical generators in healthy subjects, with more anterior generators for slow spindles.

The gating role of the thalamus to protect sleep: An f-MRI report

abstract 2011 Elsevier B.V. All rights reserved. 1. Introduction to the caseA recent technique to visually depict brain activity is functionalmagnetic resonance imaging (fMRI). Up to now, its potentiality hasrarely been deployed to study the sleep/wake cycle [1,2]. fMRI is anon-invasive technique that allows functional mapping of thebrain and is performed using blood oxygenation level dependent(BOLD) contrast imaging based on the magnetic properties ofhemoglobin. The method relies on changes in the blood supply tothe brain. The change in venous blood volume induced by neuralactivity is one critical component of BOLD signal. In short, BOLDmodifications underscore ongoing metabolic activity in a specificbrain region.We report two cases of normal subjects who incidentally fellasleepduringanfMRIsessionwhilewewereinvestigatingtheeffectofelectricalstimulationatthemediannerveonthecontralateralso-mato-sensory cortex. Here, we describe the observed activations.2. Image analysisTwo healthy right-handed subjects (aged 31 and 35 years) wereelectrically stimulated at the right median nerve at the wrist at afrequency of 3 and 10 Hz with a block design. MRI data wereacquired on a 3 T scanner (MAGNETOM Allegra, Siemens, Erlangen,Germany). Functional data were analyzed using BrainVoyager (QX