From single units to local field potentials: Study of the timing of medial temporal lobe responses in humans
Lead Research Organisation:
University of Leicester
Department Name: Engineering
Abstract
It has been shown that neurons in the human ‘hippocampus‘, an area at the end of the pathway for processing sensory information, respond significantly later than in monkeys. A possible explanation is that this is due to the fact that humans process sensory stimuli much further to create abstract concepts and associations. But how does the brain keep the timing of these responses? How do these neurons know when to fire?
To address this question, I will use recordings with intracranial electrodes placed in the brain of epileptic patients for clinical reasons. I will thoroughly study the temporal dynamics of the neural responses both in terms of the firing of individual neurons and the average activity of a large number of neurons, leading to the so called Local Field Potentials (LFPs). Particularly, I will explore whether the LFPs provide the timing information in the areas under study. Using different experimental manipulations, I will explore the consequences in the neural responses of variations of the timing for recognition and given that these areas are critical for memory storage, these finding may have long term relevance for improving our understanding on memory formation and memory disorders, such as Alzheimer‘s disease.
To address this question, I will use recordings with intracranial electrodes placed in the brain of epileptic patients for clinical reasons. I will thoroughly study the temporal dynamics of the neural responses both in terms of the firing of individual neurons and the average activity of a large number of neurons, leading to the so called Local Field Potentials (LFPs). Particularly, I will explore whether the LFPs provide the timing information in the areas under study. Using different experimental manipulations, I will explore the consequences in the neural responses of variations of the timing for recognition and given that these areas are critical for memory storage, these finding may have long term relevance for improving our understanding on memory formation and memory disorders, such as Alzheimer‘s disease.
Technical Summary
The focus of this project is to study the temporal dynamics of the responses of Medial Temporal Lobe (MTL) neurons in humans. The neuronal responses are recorded by means of deep electrodes implanted in epileptic patients for clinical reasons. These electrodes can record the activity of single cells (spikes) or the average activity generated by a large number of neurons, leading to the so called Local Field Potentials (LFPs). It has been shown that neurons in MTL provide an abstract representation of the stimulus (e.g. picture presentations) since they respond to a given concept in disregarding the details of the particular picture shown. These responses consistently appear 300 ms after stimulus presentation, but how the brain manages to keep track for the post-stimulus timing and elicit such time-locked responses is still largely unknown and will be the main research question of this project.
The initial hypothesis is that LFPs may act as a gating mechanism for the single cell responses to appear. I will first characterize LFP latencies and their relation to spikes (multi and single unit) in human MTL in response to picture presentations. In addition, I plan to analyse the contributions of spikes, LFPs, and the information carried by both together using the information theory formalism.
I will also study the effect of stimulus recognition on the temporal dynamics of spiking and LFP activity. For this, the experimental paradigm will be modified to make recognition more difficult, i.e., delaying the onset of recognition by the subjects. The results of the analysis of these latencies will be compared with the ones from the first paradigm. The key question is whether a change in the behavioral response time will be correlated with a delay in the spikes and the ‘gating responses‘ of the LFPs. These results would be of large relevance because they can provide conclusive evidence about the roles of the LFPs for providing timing information in high order human brain areas.
The initial hypothesis is that LFPs may act as a gating mechanism for the single cell responses to appear. I will first characterize LFP latencies and their relation to spikes (multi and single unit) in human MTL in response to picture presentations. In addition, I plan to analyse the contributions of spikes, LFPs, and the information carried by both together using the information theory formalism.
I will also study the effect of stimulus recognition on the temporal dynamics of spiking and LFP activity. For this, the experimental paradigm will be modified to make recognition more difficult, i.e., delaying the onset of recognition by the subjects. The results of the analysis of these latencies will be compared with the ones from the first paradigm. The key question is whether a change in the behavioral response time will be correlated with a delay in the spikes and the ‘gating responses‘ of the LFPs. These results would be of large relevance because they can provide conclusive evidence about the roles of the LFPs for providing timing information in high order human brain areas.