Neural Correlates of visual perception and behaviour: Analysis of multiple single-neuron recordings in humans

Lead Research Organisation: University of Leicester
Department Name: Engineering

Abstract

Patients suffering from severe epilepsy that do not improve with medication may be considered for a surgical intervention to remove the seizure originating area. Based on clinical criteria, these patients may be implanted with intracranial electrodes to accurately localize the focus of the seizures and evaluate the potential outcome of the surgery.

Since recently, a setup unique in Europe is in place at King?s College London that from the intracranial electrodes allows not only the recording of EEG but also of multiple single-neurons. From the activity of these neurons, we plan to study whether it is possible to predict the onset of epileptic seizures. This has large clinical potential to develop seizure-warning devices or closed loop systems that can preclude the onset of the impending seizures (e.g. using a fast-acting drug or microstimulation). Previous studies at this respect have been inconclusive because they used EEG recordings, which have inherent major limitations due to their poor spatial resolution and high complexity. This will be the first time that such study is done using the activity of single cells.

Besides its clinical importance, the recording setup at King?s College London allows the unique opportunity to record directly the activity of single neurons in awake and behaving human subjects, who can report and give details of their perception and behaviour in different tasks and brain states.
Using simple experimental paradigms, we plan to address one of the most fascinating and puzzling questions in neuroscience: how do neurons in the brain represent conscious visual perception? For this, we will study the activity of neurons while the subjects see different pictures. Then we will evaluate whether the neurons increase their firing in response to particular pictures and whether these responses change if the pictures are recognized or not.

Technical Summary

For clinical reasons we can record directly the activity of single neurons in humans. These recordings are performed in epileptic patients refractory to medication, who are implanted with intracranial electrodes to evaluate the feasibility of curative surgery. Besides its clinical importance, this procedure allows the unique opportunity to record directly the activity of single neurons in awake and behaving human subjects, who can report and give details of their perception and behaviour in different tasks and brain states.

Our overall aims are: i) to study how visual information and behaviour are represented by populations of neurons in the human brain, and ii) to study the mechanisms of epileptic seizures and the possibility of seizure forecasts for clinical applications.

For the first aim, a large set of pictures will be presented several times on a laptop computer while recording the neuronal activity. Pictures will be shown in conditions of difficult recognition (using short presentation times and noise) so that they will be recognized in some of the trials and not recognized in some other. Then, we will assess whether the firing of the responsive neurons is stronger when the pictures are recognized, thus reflecting conscious perception, or whether they keep the same firing for recognized and not-recognized trials, thus reflecting unconscious visual processing. The information obtained from the firing of single-cells will be compared to the one obtained from local field potentials using a decoding approach.

For the second aim, we will first characterize changes in the firing of the neurons and their connectivity patterns during seizures and pre-seizures states, in comparison with the activity during inter-ictal states. Based on this information we will then evaluate the possibility of predicting the seizure onsets. We will focus on forecasts of at least minutes in advance, which should give an adequate time window for realistic clinical applications. Predictions obtained with the multiple single-neurons will be compared to those obtained with the intracranial EEGs.

Finally, we plan to develop and optimize further advanced methods to analyze the single-cell data. The general goal is to record as many neurons as possible from each electrode in an unsupervised way and eventually on-line. These developments will be tested using extensive computer simulations mimicking the activity of large neural populations.

Publications

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Alarcón G (2012) In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation. in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

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Berger TW (2010) Signal processing for neural spike trains. in Computational intelligence and neuroscience

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Campi, J (2015) Neuronal encoding of memory in the human and mouse hippocampus. in European Journal of Neurodegenerative Disease

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Eichele T (2008) Unmixing concurrent EEG-fMRI with parallel independent component analysis. in International journal of psychophysiology : official journal of the International Organization of Psychophysiology

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Ison MJ (2008) Selectivity and invariance for visual object perception. in Frontiers in bioscience : a journal and virtual library

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Jongsma ML (2012) Event related potentials to digit learning: tracking neurophysiologic changes accompanying recall performance. in International journal of psychophysiology : official journal of the International Organization of Psychophysiology

 
Description BBSRC
Amount £779,102 (GBP)
Funding ID BB/H014047/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2010 
End 12/2013
 
Description EP/H051651/1 Ultra Low Power Implantable Platform for Next Generation Neural Interfaces
Amount £321,028 (GBP)
Funding ID EP/H051651/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 02/2010 
End 02/2014
 
Description Intracraneal Recordings in humans: Study of memory processes and applications to neural prostheses
Amount £297,583 (GBP)
Funding ID G0902089 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 12/2010 
End 11/2013
 
Description MRC G1002100 From single units to local field potentials: Study of the timing of medial temporal lobe responses in humans
Amount £295,333 (GBP)
Funding ID G1002100 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 10/2015
 
Title Wave_clus software 
Description Wave_clus, a new method for processing neural data (spike sorting) is available online in a dedicated webpage with all the codes, tutorials, help files, etc. 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact Currently this software is the most used method for spike sorting. The dedicated webpage (for spike sorting) has the largest number of hits in google. The paper describing the method is the most cited spike sorting paper according to ISI 
URL https://www2.le.ac.uk/centres/csn/research-2/spike-sorting
 
Description Kings College London 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Kings College London are our collaborators in this MRC grant. Together we are setting up a new single cell recording system for humans and we are performing experiment to study responses to perception and behavious.
Collaborator Contribution Provide access to patients for performing recordings.
Impact The system is set in London and we are currently performing experiments and collecting data.
Start Year 2008
 
Description UCLA 
Organisation University of California, Los Angeles (UCLA)
Department Department of Neurosurgery
Country United States 
Sector Academic/University 
PI Contribution Recordings and analysis of data
Collaborator Contribution Provision of patients, recording facilities
Impact Papers. Common projects.
 
Description Contact with the media (newspapers, radio interviews, tv interviews etc) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact My papers led to large number of press releases. For details see http://www2.le.ac.uk/departments/engineering/research/bioengineering/neuroengineering-lab/news-events

Research in my lab having wide disemination to general public
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description National and International conferences 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Attendance and presentations at both national and international conferences, including SFN 2013, 2014, 2015 and FENS 2012, 2016.
Year(s) Of Engagement Activity 2012,2013,2014,2015,2016