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.

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 brainas.

Publications

10 25 50
 
Description Santander Travel Award
Amount £570 (GBP)
Organisation Santander UK Ltd. 
Sector Private
Country United Kingdom
Start 07/2015 
End 07/2016
 
Title A new tool to analyse continuous electrophysiological data 
Description A new tool to analyse continuous electrophysiological data by extracting information to discriminate different experimental conditions 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact Just became publicly available so impact cannot yet be assessed 
URL https://doi.org/10.1016/j.jneumeth.2017.12.014
 
Title A new version of Wave Clus 
Description A new version of Wave Clus has been developed. It is not only fully automatic but it also outperforms the old version with manual supervision 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact A manuscript has been recently submitted for publication so impact cannot yet be assessed 
 
Title A new version of Wave Clus, a widely used spike sorting tool 
Description A new version of Wave Clus, a widely used spike sorting tool 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact A new version of Wave Clus, a widely used spike sorting tool. Several improvements were done and bugs were fixed 
URL https://github.com/csn-le/wave_clus
 
Title A large set of simulated recordings from single channels with different number of neurons 
Description A large set of simulated recordings from single channels with different number of neurons that can be used to evaluate spike sorting methods 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact The database has already been used by colleagues to evaluate novel spike sorting methods 
URL http://bioweb.me/CPGJNM2012-dataset
 
Title A large set of simulated tetrode recordings with different number of neurons 
Description A large set of simulated tetrode recordings with different number of neurons that can be used to evaluate spike sorting methods 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact The set has been recently created and it willl soon be placed in a public repository. The impact cannot be yet assessed 
 
Description Presentation at "Lates" in the Science Museum (London, UK) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Together with Dr Matias Ison, we presented our work at the Lates event in April 2016. We implemented an interactive activity where the public could perform the same task our patients normally perform and they received feedback from real neural activity recorded during that task. We showed how single neurons in the brain were able to encode new associations between arbitrary stimuli
Year(s) Of Engagement Activity 2016
 
Description Presentation at the Blackrock booth during the 2016 Annual Meeting of the Society of Neuroscience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I presented at the Blackrock booth to show my experience using the Blackrock system to record single neurons in patients undergoing 24/7 invasive recordings for epilepsy diagnosis.
Year(s) Of Engagement Activity 2016
 
Description Press interview about the work published in 2014 in Current Biology 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Science 2.0 covered the work I published in 2014 showing a timing mechanism in the medial temporal lobe in humans to trigger concept neuron responses
Year(s) Of Engagement Activity 2014
URL http://www.science20.com/news_articles/time_memories-128315