Giulia Varotto

Enhanced frontocentral EEG connectivity in photosensitive generalized epilepsies: a partial directed coherence study.

Purpose:  Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy presenting with electroencephalography (EEG) paroxysms elicited by intermittent photic stimulation (IPS). To investigate whether the neuronal network undergoes dynamic changes before and during the transition to an EEG epileptic discharge, we estimated EEG connectivity patterns in photosensitive (PS) patients with idiopathic generalized epilepsy.

Identification of the Epileptogenic Zone from Stereo-EEG Signals: A Connectivity-Graph Theory Approach

In the context of focal drug-resistant epilepsies, the surgical resection of the epileptogenic zone (EZ), the cortical region responsible for the onset, early seizures organization, and propagation, may be the only therapeutic option for reducing or suppressing seizures. The rather high rate of failure in epilepsy surgery of extra-temporal epilepsies highlights that the precise identification of the EZ, mandatory objective to achieve seizure freedom, is still an unsolved problem that requires more sophisticated methods of investigation. Despite the wide range of non-invasive investigations, intracranial stereo-EEG (SEEG) recordings still represent, in many patients, the gold standard for the EZ identification. In this contest, the EZ localization is still based on visual analysis of SEEG, inevitably affected by the drawback of subjectivity and strongly time-consuming. Over the last years, considerable efforts have been made to develop advanced signal analysis techniques able to improve the identification of the EZ. Particular attention has been paid to those methods aimed at quantifying and characterizing the interactions and causal relationships between neuronal populations, since is nowadays well assumed that epileptic phenomena are associated with abnormal changes in brain synchronization mechanisms, and initial evidence has shown the suitability of this approach for the EZ localization. The aim of this review is to provide an overview of the different EEG signal processing methods applied to study connectivity between distinct brain cortical regions, namely in focal epilepsies. In addition, with the aim of localizing the EZ, the approach based on graph theory will be described, since the study of the topological properties of the networks has strongly improved the study of brain connectivity mechanisms.

Abnormal ERD/ERS but unaffected BOLD response in patients with Unverricht-Lundborg disease during index extension: a simultaneous EEG-fMRI study.

Electrophysiological studies indicate that Unverricht–Lundborg’s disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.

From brain topography to brain topology: relevance of graph theory to functional neuroscience

Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer’s disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians.

Music and emotion: An EEG connectivity study in patients with disorders of consciousness

Human emotion perception is a topic of great interest for both cognitive and clinical neuroscience, but its electrophysiological correlates are still poorly understood. The present study is aimed at evaluating if measures of synchronization and indexes based on graph-theory are a tool suitable to study and quantify electrophysiological changes due to emotional stimuli perception. In particular, our study is aimed at evaluating if different EEG connectivity patterns can be induced by pleasant (consonant) or unpleasant (dissonant) music, in a population of healthy subjects, and in patients with severe disorders of consciousness (DOCs), namely vegetative state (VS) patients.

Partial Directed Coherence estimated on Stereo-EEG signals in patients with Taylor's type focal cortical dysplasia

The study was aimed at evaluating the changes in dynamical connectivity, between interictal, preictal and ictal condition, among signals derived from StereoEEG recordings in patients with Taylors type focal cortical dysplasia (FCD type-II), by means of Partial Directed Coherence and indexes derived from graph theory. Results showed that seizures are characterized by an increased synchronization, mainly within the regions involved in the generation of the epileptogenic activity. Our findings reveal that the proposed procedure can be considered a suitable techinque to properly identify the pathological synchronization mechanisms underlying seizure generation and to support the identification of the epileptogenic zone.

Simultaneous EEG-fMRI in patients with unverricht-lundborg disease: event-related desynchronization/synchronization and hemodynamic response analysis

We performed simultaneous acquisition of EEG-fMRI in seven patients with Unverricht-Lundborg disease (ULD) and in six healthy controls using self-paced finger extension as a motor task. The event-related desynchronization/synchronization (ERD/ERS) analysis showed a greater and more diffuse alpha desynchronization in central regions and a strongly reduced post-movement beta-ERS in patients compared with controls, suggesting a significant dysfunction of the mechanisms regulating active movement and movement end. The event-related hemodynamic response obtained from fMRI showed delayed BOLD peak latency in the contralateral primary motor area suggesting a less efficient activity of the neuronal populations driving fine movements, which are specifically impaired in ULD.

EEG-EMG coherence estimated using time-varying autoregressive models in movement-activated myoclonus in patients with progressive myoclonic epilepsies.

We aimed this study at verifying the appropriateness of bivariate time-varying autoregressive models in detecting EEG-EMG relationships and identifying the characteristics of myoclonus-related EEG changes in patients with two forms of progressive myoclonus epilepsy (PME). Our results indicate that TVAR analysis was able to detect the presence of prominent peaks of EEG-EMG coherence between the EMG and contralateral frontocentral EEG derivation in all patients, revealing differences in time-frequency spectral profiles associated to the two different forms of PMEs, possibly correlated with the severity of myoclonus.

Network characteristics in benign epilepsy with centro-temporal spikes patients indicating defective connectivity during spindle sleep: A partial directed coherence study of EEG signals

OBJECTIVE To investigate the changes in EEG connectivity in children with the typical presentation of benign epilepsy with centro-temporal spikes (BECTS). METHODS We compared awake and spindle-sleep EEG recordings obtained by a standard electrode array in patients with lateralised (10 Right, 9 Left-BECTS) or bilateral spikes (10 MF-BECTS) and in 17 age-matched controls. We analysed EEG activity using partial directed coherence, an estimator of connectivity based on the multivariate autoregressive models and calculated in- and out-degrees, strength, clustering coefficient and betweenness centrality. RESULTS In comparison with the controls, the awake EEG recordings of the patients with lateralised BECTS showed a minimal increase in out-degrees on F4 and F3. The greater differences, found during sleep, included significant reductions in both in- and out-degrees and strength in all of the patient groups, but in T4 or T3 showing increased out-degrees and strength in Right and Left-BECTS. Betweenness centrality was significantly reduced on C3 and C4 in the patients with MF-BECTS. CONCLUSIONS Our observations suggest that the main finding in BECTS patients is widely reduced local connectivity. SIGNIFICANCE The network changes in BECTS can be interpreted as a permissive condition occurring in a developmental window that predisposes to seizure generation during spindle-sleep.

P23-14 Action myoclonus in sialidosis: a comparative study with Unverricht-Lundborg disease

clinical diagnosis of this condition (7 men and 9 women, mean age of 51±18 years). For normal control, 19 aged-matched healthy subjects (11 men and 8 women, mean age of 49±18 years) were studied. Results: Fourteen out of 16 patients showed giant SEPs. P25 and N35 amplitudes in the patient group were 11.5±6.4mV and 18.9±11.6mV, respectively, and both were significantly larger compared with normal controls (P< 0.05). There was a significant positive correlation between age at SEP examination and N20, P25 and N35 amplitudes both in the patient and normal groups (P< 0.05). The linear regression gradient of N35 amplitude with respect to the age was significantly larger in the patient group than in the normal control groups (P< 0.05). Furthermore, older patients showed significantly severer myoclonus than younger patients (P< 0.05). Conclusions: Therefore, SEP amplitude increases with age in patients with BAFME to a greater extent than in normal controls, and it may suggest a progressive increase in cortical excitability based on progressive pathophysiology in BAFME.