Learning, Memory and Networks in the Human Brain: Single Neuron Recordings in Depth-electrode Candidates for Epilepsy Surgery

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.

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.

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.

The burden for patients in this study consists of three neuropsychological
tests per day during their stay at the Epilepsy Monitoring Unit. To our
knowledge, no health risks are involved due to the implementation of
microelectrodes, as depth macroelectrodes are already being used for clinical
purposes.