Evgenia Sitnikova

Wavelets in Neuroscience

MathematicalMethods of Signal Processing in Neuroscience.- Brief Tour of Wavelet Theory.- Analysis of Single Neuron Recordings.- Classification of Neuronal Spikes from Extracellular Recordings.- Wavelet Approach to the Study of Rhythmic Neuronal Activity.- Time-Frequency Analysis of EEG: From Theory to Practice.- Automatic Diagnostics and Processing of EEG.- Conclusion.- Index.

Granger causality: Cortico-thalamic interdependencies during absence seizures in WAG/Rij rats

Linear Granger causality was used to identify the coupling strength and directionality of information transport between frontal cortex and thalamus during spontaneous absence seizures in a genetic model, the WAG/Rij rats. Electroencephalograms were recorded at the cortical surface and from the specific thalamus. Granger coupling strength was measured before, during and after the occurrence of spike-wave discharges (SWD). Before the onset of SWD, coupling strength was low, but associations from thalamus-to-cortex were stronger than vice versa. The onset of SWD was associated with a rapid and significant increase of coupling strength in both directions. There were no changes in Granger causalities before the onset of SWD. The strength of thalamus-to-cortex coupling remained constantly high during the seizures. The strength of cortex-to-thalamus coupling gradually diminished shortly after the onset of SWD and returned to the pre-SWD level when SWD stopped. In contrast, the strength of thalamus-to-cortex coupling remained elevated even after cessation of SWD. The strong and sustained influence of thalamus-to-cortex may facilitate propagation and maintenance of seizure activity, while rapid reduction of cortex-to-thalamus coupling strength may prompt the cessation of SWD. However, the linear estimation of Granger coupling strength does not seem to be sufficient for predicting episodes with absence epilepsy.

On the Origin and Suddenness of Absences in Genetic Absence Models

The origin of spike-wave discharges (SWDs), typical for absences, has been debated for at least half a century. While most classical views adhere to a thalamic oscillatory machinery and an active role of the cortex in modifying normal oscillations into pathological SWDs, recent studies in genetic models such as WAG/Rij and GAERS rats have challenged this proposal. It seems now well established that SWDs originate from the deep layers of the somatosensory cortex, that the activity quickly spreads over the cortex and invades the thalamus. The reticular thalamic nucleus and other thalamic nuclei provide a resonance circuitry for the amplification, spreading and entrainment of the SWDs. Conclusive evidence has been found that the changed functionality of HCN1 channels is a causative factor for the changes in local excitability and age-dependent increase in SWD. Furthermore, upregulation of two subtypes of Na+ channels, reduction of GABAB and mGlu 2/3 receptors might also play a role in the local increased excitability in WAG/Rij rats. Signal analytical studies have also challenged the view that SWDs occur suddenly from a normal background EEG. SWDs are recruited cortical responses and they develop from increasing associations within and between cortical layers and subsequently subcortical regions, triggered by the simultaneous occurrence of theta and delta precursor activity in the cortex and thalamus in case both structures are in a favorable condition, and increased directional coupling between cortex and thalamus. It is hypothesized that the cortex is the driving force throughout the whole SWD and is also responsible for its end.

Time-frequency characteristics and dynamics of sleep spindles in WAG/Rij rats with absence epilepsy.

In rat models of absence epilepsy, epileptic spike-wave discharges appeared in EEG spontaneously, and the incidence of epileptic activity increases with age. Spike-wave discharges and sleep spindles are known to share common thalamo-cortical mechanism, suggesting that absence seizures might affect some intrinsic properties of sleep spindles. This paper examines time-frequency EEG characteristics of anterior sleep spindles in non-epileptic Wistar and epileptic WAG/Rij rats at the age of 7 and 9 months. Considering non-stationary features of sleep spindles, EEG analysis was performed using Morlet-based continuous wavelet transform. It was found, first, that the average frequency of sleep spindles in non-epileptic Wistar rats was higher than in WAG/Rij (13.2 vs 11.2 Hz). Second, the instantaneous frequency ascended during a spindle event in Wistar rats, but it was constant in WAG/Rij. Third, in WAG/Rij rats, the number and duration of epileptic discharges increased in a period between 7 and 9 months of age, but duration and mean value of intra-spindle frequency did not change. In general, age-dependent aggravation of absence seizures in WAG/Rij rats did not affect EEG properties of sleep spindles; it was suggested that pro-epileptic changes in thalamo-cortical network in WAG/Rij rats might prevent dynamic changes of sleep spindles that were detected in Wistar.

Thalamo-cortical mechanisms of sleep spindles and spike—wave discharges in rat model of absence epilepsy (a review)

According to the most generally accepted cortico-reticular theory of absence epilepsy, sleep spindles and spike-wave discharges (SWD, characteristic hallmarks of absence epilepsy) are closely related. The present review critically evaluates this theory based on the original data obtained in WAG/Rij rat model of absence epilepsy. It is demonstrated that (1) sleep spindles and spike-wave discharges are distinguished in time-frequency domain. (2) EEG waveforms of sleep spindles and SWD are underlain by different synaptic processes, as determined with the aid of computational neuronal model of cortical field potentials. (3) Sleep spindles do not precede SWD. EEG analysis of SWD-precursor activity provides us with a clue to possible prediction of absence epilepsy episodes. Furthermore, by studying Granger causality and EEG coherence at the onset of SWD we gain more insight into the dynamics of the thalamo-cortical neuronal network associations that underlie occurrence of absence seizures. In general, spindle activity and SWD display different time-frequency characteristics as measured in cortex and thalamus, they are accompanied by different neuronal processes and require different involvement of neurotransmitters. Sleep spindles and SWD are considered as autonomous EEG phenomena, and straightforward relationship between them is doubtful.

Electroencephalographic precursors of spike-wave discharges in a genetic rat model of absence epilepsy: Power spectrum and coherence EEG analyses

Periods in the electroencephalogram (EEG) that immediately precede the onset of spontaneous spike-wave discharges (SWD) were examined in WAG/Rij rat model of absence epilepsy. Precursors of SWD (preSWD) were classified based on the distribution of EEG power in delta-theta-alpha frequency bands as measured in the frontal cortex. In 95% of preSWD, an elevation of EEG power was detected in delta band (1-4Hz). 73% of preSWD showed high power in theta frequencies (4.5-8Hz); these preSWD might correspond to 5-9Hz oscillations that were found in GAERS before SWD onset [Pinault, D., Vergnes, M., Marescaux, C., 2001. Medium-voltage 5-9Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons. Neuroscience 105, 181-201], however, theta component of preSWD in our WAG/Rij rats was not shaped into a single rhythm. It is concluded that a coalescence of delta and theta in the cortex is favorable for the occurrence of SWD. The onset of SWD was associated with strengthening of intracortical and thalamo-cortical coherence in 9.5-14Hz and in double beta frequencies. No features of EEG coherence can be considered as unique for any of preSWD subtype. Reticular and ventroposteromedial thalamic nuclei were strongly coupled even before the onset of SWD. All this suggests that SWD derive from an intermixed delta-theta EEG background; seizure onset associates with reinforcement of intracortical and cortico-thalamic associations.

Application of adaptive nonlinear Granger causality: disclosing network changes before and after absence seizure onset in a genetic rat model.

BACKGROUND Advanced methods of signal analysis of the preictal and ictal activity dynamics characterizing absence epilepsy in humans with absences and in genetic animal models have revealed new and unknown electroencephalographic characteristics, that has led to new insights and theories. NEW METHOD Taking into account that some network associations can be considered as nonlinear, an adaptive nonlinear Granger causality approach was developed and applied to analyze cortico-cortical, cortico-thalamic and intrathalamic network interactions from local field potentials (LFPs). The outcomes of adaptive nonlinear models, constructed based on the properties of electroencephalographic signal and on statistical criteria to optimize the number of coefficients in the models, were compared with the outcomes of linear Granger causality. RESULTS The nonlinear adaptive method showed statistically significant preictal changes in Granger causality in almost all pairs of channels, as well as ictal changes in cortico-cortical, cortico-thalamic and intrathalamic networks. Current results suggest rearrangement of interactions in the thalamo-cortical network accompanied the transition from preictal to ictal phase. COMPARISON WITH EXISTING METHOD(S) The linear method revealed no preictal and less ictal changes in causality. CONCLUSIONS Achieved results suggest that this proposed adaptive nonlinear method is more sensitive than the linear one to dynamics of network properties. Since changes in coupling were found before the seizure-related increase of LFP signal amplitude and also based on some additional tests it seems likely that they were not spurious and could not result from signal to noise ratio change.

Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

Coexistence of intermittencies in the neuronal network of the epileptic brain.

Intermittent behavior occurs widely in nature. At present, several types of intermittencies are known and well-studied. However, consideration of intermittency has usually been limited to the analysis of cases when only one certain type of intermittency takes place. In this paper, we report on the temporal behavior of the complex neuronal network in the epileptic brain, when two types of intermittent behavior coexist and alternate with each other. We prove the presence of this phenomenon in physiological experiments with WAG/Rij rats being the model living system of absence epilepsy. In our paper, the deduced theoretical law for distributions of the lengths of laminar phases prescribing the power law with a degree of -2 agrees well with the experimental neurophysiological data.

Reduction of epileptic spike-wave activity in WAG/Rij rats fostered by Wistar dams

In WAG/Rij rat genetic model of absence epilepsy, the first spike-wave discharges (EEG hallmark of absence epilepsy) are known to appear after puberty, and their incidence increases with age. WAG/Rij rats are known to have a genetic predisposition to absence epilepsy, and further development of epilepsy might be influenced by epigenetic factors. This preliminary study examined the effect of early postnatal factors on the incidence of epileptic spike-wave discharges in adulthood. The newborn WAG/Rij rats were fostered by Wistar dams (from birth throughout the weaning age), and their EEG was examined continuously from 5 to 13 months of age. It was found that the number and duration of absence seizures was reduced in WAG/Rij rats adopted by Wistar dams as compared with the age-matched control WAG/Rij rats nursed by their own mothers. These data indicate that natural (epigenetic) factors, such as maternal care during suckling period, affect development of seizure activity in genetically prone subjects. It is suggested that improvement of primarily care-giving environment in subjects with genetic predisposition to absence epilepsy is a way to reduce epileptic activity in later life.