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Neurophysiology and Behavior: Spike Trains and Fields
David Moorman
Psychological and Brain Sciences
Neuroscience and Behavior Graduate Program
University of Massachusetts Amherst
CCNS: Challenges in Functional Connectivity Modeling and Analysis 2016
How to Read Character: A New
Illustrated Hand-Book of Phrenology
and Physiognomy, for Students and
Examiners; with a Descriptive Chart.
(New York, Fowler & Wells Co.,
Pubs., 1891)
Neural circuitry presents a complex view of the brain
MGH Human connectome project acquisition team,
Sanes, Lichtman, et al., Brainbow/Brainstorm Consortium
Cellular neural circuitry is even more complex
Singh 2012
Presentation Outline
• Brief background
• Biological basis of neural signals and how data are collected
• Different types of neural signals• Synaptic potentials/currents (briefly)
• Spikes/action potentials
• Local Field Potentials (LFP)
• EEG (briefly)
• Association of neural signals with behavior
• Relationship to BOLD signal
• Analysis of neural signals
• Future directions and challenges going forward
Some caveats
• Pace of presentation (slow)
• My research focus (minimized)
• My areas of expertise (and lack thereof)
• Happy to look into anything that I can’t address here
The problem
Information (sensory,
etc.)
Neural processing
Information transformation
Cognition
Action, behavior
Which level of analysis?
Rosie Cowell
Gazzaniga 2009
General THM
• Information is conveyed through neuronal activity• Contributions of non-neuronal cells (glia, etc.)?
• Neuron ensemble activity encodes information• Within brain areas• Across brain areas
• Neural code is complex• Spikes?• Fields?
• Neural data sets can be enormous and heterogeneous
• Neurons/ensembles themselves are highly heterogeneous• Periodic “check-ins” with biology
fMRI
Gazzaniga 2009
“…it’s like looking down at the US from a satellite seeing the grid of lights at night. You can infer certain things: Here’s a city, here’s a city. But to really understand the interactions between those cities you need to get down to the level of individual people moving around in cars. It’s a matter of scale and resolution.” -- Bill Newsome, Wired, 2013
“It makes no sense to read a newspaper with a microscope.” -- Valentino Braitenburg (quoted in Logothetis 2008)
Switfyscience.blogspot.com
Lent et al., 2012
• Approximately 1000 Trillion synapses
• Approximately 10^5 “switches” per synapse (channels, receptors, transporters)
• So approximately 10^20 “switches” per brain
Stephen Smith
How many neurons per voxel?
https://cfn.upenn.edu/aguirre/wiki/public:neurons_in_a_voxel
Lent et al., 2012
• Approximately 1000 Trillion synapses
• Approximately 10^5 “switches” per synapse (channels, receptors, transporters)
• So approximately 10^20 “switches” per brain
Stephen Smith
Each medium spiny neuron receives input from several thousand excitatory cortical neurons
Striatal medium spiny neuron
Lynn Raymond, UBC
Logothetis 2008
Logothetis 2008
Presentation Outline
• Brief background
• Biological basis of neural signals and how data are collected
• Different types of neural signals• Synaptic potentials/currents (briefly)
• Spikes/action potentials
• Local Field Potentials (LFP)
• EEG (briefly)
• Association of neural signals with behavior
• Relationship to BOLD signal
• Analysis of neural signals
• Future directions and challenges going forward
theremino.com
http://www.mtchs.org/BIO/text/chapter28
http://www.mtchs.org/BIO/text/chapter28
http://www.mtchs.org/BIO/text/chapter28
https://www.studyblue.com/notes/note/n/chapter-48-nervous-system/deck/4169450
techlab.bu.edu
http://www.interactive-biology.com/99/the-isoelectric-point-and-how-it-leads-to-an-action-potential/
Action potential (spikes) are the output from cell bodies/axons
http://www.qbi.uq.edu.au/brain-facts/neuroscience-basics-action-potentials-and-synapses
www.ruhr-uni-bochum.de
syntheticneurobiology.org
Extracellular electrophysiological recording
Moorman and Aston-Jones, 2010
Dendrite (input)
Axon (output)
Soma (cell body)
newton.umsl.edu
Rolston et al., 2009
Raw electrical signals are filtered into different types of neural activity
http://lifesciences.ieee.org/publications/newsletter/april-2012 - M. Mollazadeh
Einevoll et al., 2012
Example of four neurons recorded from one electrode wire in rat prefrontal
cortex
Courtesy of Lex Kravitz
Recording the activity of more than one neuron or field location
Chapter 1, State-of-the-Art Microwire Array Design for Chronic Neural Recordings in Behaving Animals
Methods for Neural Ensemble Recordings. 2nd edition.
Nicolelis MAL, editor.
Electrodes are implanted in the brain and connected to amplifiers and
filters
Rolston et al., 2009
Wireless recording of multiple neurons
Szutz et al., 2011
From: Chapter 5, Chronic Recordings in Transgenic Mice
Methods for Neural Ensemble Recordings. 2nd edition.
Nicolelis MAL, editor.
Stuart Layton, Wikipedia
Tetrodes are used to precisely isolate multiple neurons
Voigts et al., 2013
Einevoll et al., 2013
Local field potentials are a summation of synaptic
input (dendrites) and neuronal population activity
Increases in LFP power at specific frequencies underlies different behavioral/cognitive functions
Wang 2010
Hopkinsmedicine.org
backyardbrains.org
backyardbrains.org
Adjamian 2014
Presentation Outline
• Brief background
• Biological basis of neural signals and how data are collected
• Different types of neural signals• Synaptic potentials/currents (briefly)
• Spikes/action potentials
• Local Field Potentials (LFP)
• EEG (briefly)
• Association of neural signals with behavior
• Relationship to BOLD signal
• Analysis of neural signals
• Future directions and challenges going forward
How does fMRI relate to electrical activity?
Logothetis et al., 2001
Using optogenetics to dissect BOLD signalsuggests spiking activity may contribute
Leopold – comment on Lee et al., 2010
Optogenetics as a tool to study neuronal function
http://neurobyn.blogspot.se/2011/01/controlling-brain-with-lasers.html Deisseroth Lab
Excitatory and inhibitory light-sensitive proteins
Deisseroth Lab
Optogenetic excitation and inhibition of neurons
Jones et al., 2015
Optogenetic control of behavior
Liang et al., 2015
Optogenetic circuit mapping in awake and
anesthetized animals
Presentation Outline
• Brief background
• Biological basis of neural signals and how data are collected
• Different types of neural signals• Synaptic potentials/currents (briefly)
• Spikes/action potentials
• Local Field Potentials (LFP)
• EEG (briefly)
• Association of neural signals with behavior
• Relationship to BOLD signal
• Analysis of neural signals
• Future directions and challenges going forward
Data analysis methods - spikes
• Action potentials = spikes
• Patterns of spikes = spike trains
• Spike trains are point processes• Though can be smoothed
• LFPs are continuous
• Most basic forms of analysis:• Peristimulus time histogram: PSTH
• Population averages
backyardbrains.org
Baranauskas 2015
Rate codes and temporal codes
Relationship of spikes to behavior: perievent histograms and rasters
Hernandez and Moorman, in prep
Multi-neuron population histograms
• Average together all the neurons that you recorded from to characterize what the brain area “does”
• This is unappealing for a number of reasons• Heterogeneity
Moorman and Aston-Jones, 2014
Moorman and Aston-Jones, 2015
Even when we characterize populations of single neurons, we look for trends
Moorman and Aston-Jones, 2014
Characterizing increased/decreased LFP power at specific frequencies during behavior
Ito et al., 2014
Issues with averaging/combining neural signals
• Neurons in a brain area don’t all do the same thing
• The same neuron may do multiple things
• Neuronal activity varies from trial to trial
• Neurons work together in populations
• Ensemble encoding may provide more information
Harris and Mrsic-Flogel 2013
What do we want to know?
• How do neurons encode information?• Reliably?• Flexibly?
• How do neurons interact with one another?
• How do ensembles of neurons interact with one another?
• Can we place a causal role on the relationships among neurons/ensembles?
More sophisticated ways of characterizing neural interactions
• Correlation• Cross correlogram, JPSTH
• Pattern analysis• E.g., triplets, more complex
patterns (e.g., synfirechains)
• Frequency analysis
• Principal/independent components analysis
Brown et al., 2004
Cross correlation
JPSTH
Maximum
likelihood
models
Cross coherence
Similarly LFPs can be analyzed for spatial and temporal correlation
Alain Destexhe and Claude Bedard (2013), Scholarpedia, 8(8):10713.
Population decoding
• Population vectors
• Reverse correlation
• Bayesian decoding
• Pattern classifier
Population vectors in the motor cortex
A. Georgopoulos
Population vector decoding of reward value in orbitofrontal cortex
Van Duuren et al., 2008
Pattern classifier decoding of prefrontal cortex information
Meyers et al., 2012
Higher level analyses over distance and time
• Granger causality
• Graph theory/rich club analysis
• Dynamic correlation
Coherence and Granger causality to show cross-structure relationships
Sirota et al., 2016
Evidence of rich club networks in neuronal activity
Nigam et al., 2016
Semiparametric models to dynamically characterize correlated activity across multiple
neurons
Shahbaba et al., 2014, Zhou et al., 2015
Scaling analyses to cope with the frontier of big data
Brain Activity Map
AKA BRAIN Initiative
Record from EVERY neuron in the brain
Neuron 2012
Science 2013
ACS Nano 2013
Neuroscience + Nanoscience
*all 86 billion of them
Can we record from every neuron?
Very large scale integration (VLSI) electrophysiology
Blanche et al., 2004Alivisatos et al., 2012
1000+ recording sites
LeafLabs/Boyden
Cellular optical imaging(2-photon calcium or voltage imaging)
http://biology.ucsd.edu/faculty/komiyama.html
Cellular optical imaging
Alivisatos et al., 2012
• Top: Conformational change
produced by Ca2+ binding.
• Middle: Diagram illustrating imaging
setup.
• Bottom: Blue lines plot movement of
an individual mouse in square and
circular arenas. Red dots mark the
animal’s position during Ca2+ events in
a specific CA1 neuron. Lower pairs of
figures show Gaussian-smoothed data.
Imaging “all” neurons from a zebrafish larva
Ahrens and Keller 2013
Nanomachines
• “Smart” wireless nanoscale transmitters
• Multiferroic antennas
• Ultrasmall nanoelectronicchips
• Nanoparticle labeling and reporting
Seo et al., 2013
Neurophysiological signals are used to control sensory and motor neural prosthetics in humans
http://www.stanford.edu/~shenoy/GroupResearchOverview.htm
Clinical applications of motor neural coding
Data analysis?
• Large Hadron Collider • ~10 petabytes/year
• One recording study of the type proposed • ~ 1 gigabyte/sec
• 4 terabytes/hour,
• 100 terabytes/day
• Compressed, this equals ~3 petabytes/year
Future Challenges
• Scale• understanding interactions among large numbers of
neurons simultaneously
• Coding• finding meaning in patterns of activity in single neurons
and ensembles of neurons
• note also modulatory signaling
• Plasticity• neuron function changes over time
• Heterogeneity• many types of neurons even within one brain area
Final thoughts
• Bridging the gap between biology/behavior-based neuroscience and computational neuroscience
• Train next generation of multidimensional quantitative neuroscientists
• However, there is a need for translation between statistical models and experimental data sets – what do the results “mean”?• In the context of biology
• This is going to get even more complicated as data sets get larger and larger