EEG

The use of electroencephalography (EEG) is a central part of current investigations of the normal and pathological brain activity, and has been in use for over 80 years.

3.1 EEG acquisition and scalp field maps

Extracellular currents originate from post-synaptic activity in the dendrites of aligned pyramidal neurons, and the generation of the synchronized post-synaptic activity causes electric fields that are measurable on the scalp surface.

To record the electric signal, EEG electrodes are placed on the scalp following an internationally accepted standard position: the 10-20 or 10-10 system (Klem et al. 1999).

Each electrode has a conventional anatomical label and number: ‘F’ for Frontal, ’T’ for temporal, ‘P’

for parietal, ’O’ for Occipital, ’C’ for central, ‘A’ for Auricular regions; even numbers are on the right, odd numbers on the left hemisphere, ‘z’ stands for midline electrodes. Different numbers of electrodes are used to register the brain activity, each of them is used in different research and clinical set-up. For example, in clinical set-up, normally 27 or 32 electrodes are used and up to 256 electrodes are used in research (normally called high-density-EEG). EEG is recorded with a sampling frequency between 250 Hz and 2000 Hz, reaching a temporal resolution in the millisecond range (Michel and Murray 2012).

EEG consists of a two-dimensional array: at each time point EEG potentials can be represented as scalp field maps, also called topographies (Murray et al. 2008). EEG recordings can be recorded with a single reference: the measured voltages from the reference electrode channel are subtracted from the other electrode channels for each time sample. The choice of the reference electrode channel can differ depending on the purpose of the EEG recording: a quite common reference is Cz (placed in the center of the head). When dealing with high density EEG analysis offline, another used reference is the common average reference, in which the average over all electrodes is subtracted from the potentials of all electrodes.

Figure 1: Example of epileptic spike recorded on hd-EEG and corresponding scalp topography.

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3.2 Brain activity recorded with EEG

Since the beginning of the EEG, in 1939, scientists were talking about “alphas” and “betas” to describe the neuronal activity. The clearest activity seen at the time were periodic oscillations around 10 Hz (indeed the most common rate for neuronal activity in an awake human), Berger called these periods Alpha Waves, everything else was called beta activity. In 1936, Delta waves [< 4 Hz]

were reported by Hoagland, Rubin, and Cameron, and Gamma waves [around 30Hz] were reported by Jesper and Andrews.

Since then, the EEG rhythms have been divided in mainly 5 frequency bands (Niedermeyer 2005):

Delta [<4Hz] often seen during deep sleep, Theta [4-7Hz], Alpha [8-12 Hz] often seen during eyes-closed wakefulness, Beta [13-30 Hz], Gamma [>30 Hz] often seen during information processing, and HFOs [>200 Hz] mainly seen in intracranial recordings.

3.3 EEG in epilepsy

In 12-50% of patients with epilepsy, EEG may be normal (Van Donselaar et al. 1992; Goodin and Aminoff 1984). Long-term and repeated EEG recordings increase the chance of recording different patterns that are considered epileptiform (Noachtar and Rémi 2009).

The epileptic activity can appear clinically and /or via neurophysiological measures. While seizures usually manifest clinically, interictal epileptic discharges (IEDs) are clinically mute but appear in EEG or magnetoencephalography (MEG) recordings. In addition, there are interictal periods without any EEG- or MEG-visible epileptic activity.

According to the ILAE, "an epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain" (Fisher et al. 2017), while an interictal event, also called spike or IED, is an intermittent, between two seizures, abnormal EEG patterns without a manifested symptomatology (Bancaud et al. 1981).

The so-called high frequency oscillations (HFO), EEG activity above 70 Hz, might be as well EEG and MEG biomarkers for epileptogenicity (Jacobs et al. 2012, 2009).

These can occur in association with IEDs but also may precede seizures. The majority of the time, HFO are localized and remain restricted to small areas of neocortex, but sometimes they can occur over larger areas which may be more indicative of epileptogenic cortex (Lemieux et al. 2011).

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Finally, periods without visible epileptic activity are considered when the clinician does not see any pathological activity both on behavioral and EEG levels.

3.3.1 Seizures

Based on the International League against Epilepsy (ILAE) classification of 2017, seizures are defined as either focal or generalized or with unknown onset. Seizures are focal (old term: “partial”) when resulting from a network limited to one hemisphere and are generalized when originating in, and rapidly engaging, bilaterally distributed network (Fisher et al. 2017).

Seizures with clinical symptoms are often only a small proportion of all abnormal electrical activity in the brain, which includes subclinical EEG/MEG seizure patterns, interictal spikes, bursts and high-frequency oscillations. It remains unclear precisely how seizures are related to this broader range of abnormal electrical activity (Karoly et al. 2016).

3.3.2 Interictal discharges

Interictal discharges arise from the synchronous firing of a hyperexcitable population of neurons and are considered an abnormal electrical phenomenon. Their configuration is short and sharp, thus, they have been termed spikes (duration 20-80ms) or sharp waves (80-200ms). Historically it is known that they are associated with epilepsy (Ayala et al. 1973; Schulze-Bonhage et al. 2011; Ward 1959), however, over the years, there has been conflicting evidence regarding the complex relationship between spiking process and ictogenesis (Avoli et al. 2006; de Curtis and Avanzini 2001).

On the one hand, increased neural excitability promotes epileptic spikes, which may reach a critical spatial or temporal density and lead to a seizure (de Curtis and Avanzini 2001; Jensen and Yaari 1988) and predictive or causal relationships between interictal spikes and ictogenesis have been reported. There is relatively little experimental evidence supporting the conjecture that spikes precede ictal onset, in particular from studies based on human tissue recordings (Avoli et al. 2006;

de Curtis and Avanzini 2001).

On the other hand, it has been reported that the spike rate is largely unchanged or even reduced prior to seizures (Engel and Ackermann 1980; Gotman and Marciani 1985; Librizzi and De Curtis 2003). This suggests that spikes may provide some protective beneficial mechanism against seizures.

The spike is often followed by a period of hyper-polarization, which may contribute to limiting the frequency of periodic interictal activity. Alternatively, spontaneous interictal discharge may provide regulatory, low-level excitation to forestall the transition to seizure (Avoli et al. 2006; de Curtis and

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Avanzini 2001). There may also be a secondary mechanism that influences patterns of both spikes and seizures.