Single neuron characteristics in epilepsy surgery candidates.

Rationale:
The present project proposes to investigate medial temporal lobe (MTL) structures that are often implicated in human epilepsy by studying network behaviour in epileptic patients using recordings from implanted depth macro- and microelectrodes. Additionally, we aim to use these recordings to study the MTL functions regarding memory and attention at the cellular level in the human brain.

Recent research advances concerning functional connectivity and network properties of the brain have indicated that these techniques may be used for epileptic source localization and to investigate factors that determine the frequency of epileptic seizures. Application of these methods in candidates for epilepsy surgery may lead to more effective treatment and improvement of surgical outcome.

Moreover, the medial temporal lobe (MTL) structures are critically involved in the functions of learning and memory. Significant research at the cellular level in animals, and with fMRI, PET and clinical cases in humans has revealed the fundamental role these structures play during memory formation and retrieval. However, studies of the mechanisms underlying these processes at the single neuron level in conscious humans are all too scarce.
The present study aims to clarify these mechanisms by measuring single neuron activity using microelectrodes in candidates for epilepsy surgery. A subset of these patients require placement of depth macroelectrodes into temporal lobe structures for chronic invasive extraoperative video-EEG monitoring. These electrodes contain microwires for recording in vivo field potentials and single cell activity under a variety of conditions.

Objective:
The first goal of the present study is to elucidate the network topology of the MTL on both large-scale and micro-scale levels with the aim of further understanding epilepsy related changes to the network structure. Additionally we will also use the inserted microwires to also investigate the cellular basis for MTL functions in humans, specifically, the neuronal basis for learning associations between different stimuli, the role of the MTL in unconscious learning, its role in spatial navigation in humans, and the effects of visual attention on MTL neurons in these human participants.

Study design:
This is a prospective observational study. We will record from both macro- and microelectrodes implanted in the brains of ten epileptic patients. The macroelectrodes will record continuously, thus recordings will take place during task performance and during resting state. Visual stimuli will be presented to patients on the screen of a laptop computer and require them to make simple behavioral responses. The neuronal data will be analyzed according to standard procedures employed in both human and non-human primates.

Study population:
The human subjects for this study are adult (>18 yrs) patients with medically refractory complex partial seizures who are being evaluated for resective surgical treatment.

Main study parameters/endpoints:
The main study parameters are the macro- and microelectrode recordings, memory testing results, attention testing results, assessing functional connectivity (SL and PLI) and neuronal brain networks (cluster coefficient and path length), seizure frequency and epilepsy burden.

We hypothesize that that single neuron recordings from depth micro-electrodes in candidates for epilepsy surgery can be used to reconstruct brain networks, and to determine the impact of epilepsy on these networks. This setup will allow us to address the following questions:

1. Are interictal networks in patients with refractory epilepsy closer to random than to small-world networks?

2. Does network structure change before onset of epileptic seizures?

3. Is there a relation between interictal network characteristics and seizure characteristics (number / duration of seizures)?

4. What is the relation between networks constructed from single cell versus local field potential recordings?

5. Are local networks from epileptogenic brain areas more random than local networks in non epileptogenic areas?



Furthermore, we hypothesize that these measurements can be used to to investigate the cellular basis for MTL functions in humans, specifically its involvement in unconscious learning, its role in spatial navigation in humans, the neuronal basis for learning associations between different stimuli, and the effects of attention on the firing rates and temporal firing patterns of these neurons.

The duration of depth electrode implantation.

N/A