Lecture 1 Single Unit Recording in Humans Flashcards
- Define Spatial Resolution
The accuracy with which one measures where it is occurring
- Define Temporal Resolution
The accuracy with which one measures when it is occurring
- EEG/ERP(Electroencephalography):
Method type:
Invasivness:
Signal Type:
Method EEG/ERP
Method Type: Recording
Invasiveness: Noninvasive
Signal Type: Electrical
- Single-cell (and multiunit recordings)
Method type:
Invasivness:
Signal Type:
Method Single-cell (and multiunit recordings)
Method Type: Recording
Invasiveness: Invasive
Signal Type: Electrical
- MEG(Magnetoencephalography)
Method type:
Invasivness:
Signal Type:
Method: MEG
Method Type: Recording
Invasiveness: Noninvasive
Signal Type: Magnetic
- TMS(Transcranial magnetic stimulation)
Method type:
Invasivness:
Signal Type:
Method: TMS
Method Type: Stimulation
Invasiveness: Noninvasive
Signal Type: Electromagnetic
- PET(Positron emission tomography)
Method type:
Invasivness:
Signal Type:
Method: PET
Method Type: Recording
Invasiveness: Invasive
Signal Type: Haemodynamic
- fMRI(Functional magnetic resonance imaging)
Method type:
Invasivness:
Signal Type:
Method: PET
Method Type: Recording
Invasiveness: Noninvasive
Signal Type: Haemodynamic
- Draw a visual representation of all the techniques used in neuroimaging with reference to the speed and locolization.
- There are two types of cells in CNS - Glial Cells and neurons: Describe Glial Cells
- More in Number (10-50 X Number of Neurons)
- Supporting neurons
- No direct role in information transmission (?)
- No role in electrical signalling
- There are 2 types of cells in the CNS Glial Cells and Nerve Cells:
Describe Nerve Cells (Neurons)
- Basic building block
- 1011 neurons
- More than 1000 varieties but with shared basic architecture
- Complexity of behavior depends less on the specialization of individual cells but more on the connectivity
- Generates electrical signals
- Communicates mainly via electrochemical fashion
- Neurons: name the four morphologically defined regions:
- Cell Body: Metabolic center, Contains nucleus, genes
- Dendrites: Receiving signals from other neurons
- Axons: Carrying signals to other neurons
- Synaptic Zone: Connection zone between neurons
- Draw the Four Componants of a Neuron:
- Describe the Action Potential:
- Constitute the signals by which the brain receives, analyzes and conveys ‘information’
- Same basic form
- Information is conveyed not by the form but by the pathways
- ~ 100 mV with 1 ms duration
- Propagated along the axon at a fixed and slow speed (m/sec)
- Action Potentials are __________ (same amplitude)
Action Potential are Nondecremental (same amplitude)
- All-or-nothing phenomenon means..
(either action potential fires at its full amplitude or doesn’t fire at all)
- Draw a digram of the action potential illustrating membrane potential on the y axis with 6 different steps labeled as well as a seperate diagram of sodium channels in 4 stages.
- Define Extracellular Recording
Assessment of the electrical activity of nerve, glial and muscle cells by means of electrodes positioned in the extracellular vicinity of the cells (outside the cell)
- Descibe the process of Extracellular Recording
- A small electrode
- Very high impedance (MΩ)
- Needs special pre-amplifier
- State some issues with extracellular recording
- Mixing of neurons / Unit isolation
- Lack of anatomical details
- Draw a diagram illustrating how extracellular spikes allow the neurons to be found by their amplitude signals.
- Describe Intracellular Recording
- Glass pipette electrode
- Pipette is filled with a solution with similar ionic composition to the intracellular fluid
- What is more useful about the Intracelluar recording compared to extracellular?
- Ideal for recording graded potential leading up to spike discharge or failure of spike discharge in a neuron
- Differentiates excitatory from inhibitory synaptic activity
- What are the issues with Intracellular recording?
Cell damage, Not very feasible in behaving animal
This is not used for humans as it damges cells.
- Draw a diagram of intracellular spikes.
- What are Complex Cells (CC)?
Complex cells receive inputs from a number of simple cells.
Like a simple cell, a complex cell will respond primarily to oriented edges and gratings, however it has a degree of spatial invariance. This means that itsreceptive field cannot be mapped into fixed excitatory and inhibitory zones. Rather, it will respond to patterns of light in a certain orientation within a large receptive field, regardless of the exact location. Some complex cells respond optimally only to movement in a certain direction.
- Draw a Directionally Selective CC illustrating how it is activated.
- Which of the following techniques offer the best spatial resolution?
A. fMRI
B. EEG
C. TMS
D. MEG
A. fMRI - can localise the brain regions much better than others.
- Choose the incorrect statement about Action Potential (AP)
A. AP is all-or-none
B. The profiles of APs of one neuron can vary depending on the state of the neuron
C. AP propagates in a nondecremental fashion
D. The duration of AP is approx. 1 ms
Wrong!
B The profiles of APs of one neuron can vary depending on the state of the neuron
Action potentials are very similar!!
- Sample Brief Question:
(a) What is an Action Potential (AP) of a neuron?
An action potential is a short-lasting event in which the electrical membranepotential of a cell rapidly rises and falls, following a consistent trajectory.
- Sample Brief Question
Briefly describe any four characteristics of AP.
- As an action potential travels down the axon, there is a change in polarity across the membrane
- Propagated along the axon at a fixed and slow speed (m/sec)
- Nondecremental (same amplitude)
- All-or-None phenomenon (either it fires at its full amplitude or doesn’t fire at all)
- Sample Brief Question
What are the major differences between an intracellular and an extracellular recording?
Intracelular can’t be performed in humans and is hard in animals.
Intracellualr allows for the action potential to be seen in far more detail.
Extracellular readings are taken from outside the cell
- Which recording is more suitable in humans?
Extracellular is far more appropriate as it does not damage the cell body.
- Single Unit recording in Humans:
Who are the subjects?
- Subjects are medical patients with pharmacologically resistant epilepsy
- Treatment Removal of brain tissues generating seizures
- Electrodes are surgically implanted to localize the focus of the seizures
- Single Unit Recording in Humans:
What is the primary target area of the brain?
MTL (mid temporal lobe) is the primary target area
– Hippoacmapus, Amygdala, Entorhinal cortex, Parahippocampal cortex
Average hospital stay = 7-14 days
- List advantages of single cell recording in humans.
- Signal source: Direct recording
- Spatial resolution: 1-2 mm (EEG ~ cm)
- Temporal resolution: ~ ms
- Signal-to-noise ratio: (less artefacts, i.e. no blink artefacts)
- High frequency brain activity
- List the three conditions for selecting a patient / participant for surgery?
- They must have failed to respond to medical management (antiepileptic drugs)
- Their quality of life would be markedly enhanced by achieving a seizure-free surgical outcome. The ideal surgical candidate is a young person whose educational and vocational opportunities promise to be enhanced substantially by eliminating seizures. These patients also are ideal subjects for invasive brain research.
- Third, their seizure focus must be localized to a circumscribed portion of the brain that can be safely removed surgically.
- Draw images of the following tools.
a) Microelectrode
b Hybrid Depth Electrodes
c) Strip Electrode
d) Research Grid electrode
e) Microgrid
- Describe Acute Recording
- No requirement of preoperative diagnostic testing
- Experiments inside the operating room
- Max duration of experiment = 30 min
- Noisy/challenging environment; no room for debugging faults Patient’s responses are limited (simple verbalization or button press) Patient is in supine position (minimal movement is allowed)
- Describe Chronic recording
- There is some residual uncertainty about the location of seizure foci
- Requirement of additional diagnostic testing (recording from electrode arrays chronically implanted)
- Experiments are carried out in a specially equipped hospital suite (less noisier than Acute recording)
- A lot of variability (devices, techniques, protocols) across epilepsy centers
- Patients are less restricted and more demanding tasks can be performed
- What is the procedure for chronic recording?
Cognitive and sensory functions are tested through testing
– Both pre- and post-operative testing are necessary in order to ensure that IQ, visual function and other factors won’t confound the data
Need to careful document the medication status of the patient
– Usually antileptic medication is lowered to increase the chance of epilepsy
– If no seizure is recorded, patient is often sleep deprived
- When are Chronic recording tests carried out?
Testing is done several days after electrode implantation
Testing window spans only for a few days when the patient is awake and alert, has minimal seizure, and not sleep- deprived
Pre- and post- MRI scans are necessary to localize electrodes
- Neuronal spike recording steps.
- Amplification (1000-5000)
- Notch Filtering (50 Hz ± 1 Hz) [60 Hz in USA]
- High-pass Filter (250-300 Hz)
- Storage on a PC
- Sampling Frequency ~ 20 kHz
Record either 1) Continuous Signal 2) Discrete signal (signal > threshold)
Note most use continuous recording now as data storage and memory is now very cheap.
- Neuronal Coding:
Define Rate Coding
- Information is in the mean firing rate of the neuron
- Most widely used and understood
- Robust for recognition and processing of static objects, – Less suitable for fast and dynamic action
- Neuronal Coding:
Define Temporal Coding
- Information is in the timing of the spike
- No precise definition, anything not based on rate can be based on timing (most important is neuronal synchronization)
- Draw an image of a threshold being applied to a neuron firing
- Describe the Spike detection - Neural Cocktail Party Problem
Imagine a room where several people are sitting and talking. The likely range of people number is known, but the precise number is not. Their language is unknown to us and sometimes several of them talk simultaneously. In our analogy these people correspond to neurons. We have placed one or several microphones in this room and now record the compound sound generated by the superposed discourses. Our task is to find out:
- How many people talk during the recording?
- What are some of the characteristics of the sounds emitted by each person (pitch of the voice, loudness, variability, statistics)?
• What is the discourse of each person?
- List some features of neurons that can help to sort the spikes.
Core features:
- Loudness - Spike amplitude (∝ 1/Electrode-distance)
- Pitch - Spike waveform
- Talkative - Firing rate
Additional features:
- Context - correlation
- Modulation of loudness by prosody
- List 4 steps for spike sorting method
- Peri-Stimulus Time Histogram (PSTH) is a simple way to show the neuronal firing pattern list the procedure.
- Align spike sequences with stimulus onset (or any event) which repeates n times
- Divide the stimulus period S into N bins of size ∆
- Count the number of spikes (ki) within individual bin for all trials
- Compute the histogram
- Do we need spike sorting?
It can be very useful as seen here where three definite neuronal patterns are sorted.
- What did Quian Quiroga et al (2005) Nature illustrate?
That even when a neuron fires only sporadically it could be down to a specific relationship to a stimulus. Eg. Certain animal visuals.
- The typical sampling frequency used for recording single neuron activity is
A. 2KHz
B. 20 KHz
C. 200 KHz
D. 200 Hz
B. 20KHz
- Which of the following features is not used in spike sorting?
A.Spike shape
B.Spike amplitude
C.Firing rate
D. Spike’s refractory period
D. Spike’s refractory period
This is universal across neurons - 1ms
- What is spike sorting?
Spike sorting is the grouping of spikes into clusters based on the similarity of their shapes. Given that, in principle, each neuron tends to fire spikes of a particular shape, the resulting clusters correspond to the activity of different putative neurons. The end result of spike sorting is the determination of which spike corresponds to which of these neurons.
- List any three features used in spike sorting.
Amplitude
Firing Rate
Pitch
- List some links between neurons and perception.
- Neurons should have discernible statistical differences in their firing patterns in response to the different external stimuli
- The firing patterns of the neurons should not be affected by the mere motor responses
- Fluctuations in the firing to the repeated presentation of identical stimuli should be predictive of the observer’ response
- Direct interference with the firing of neurons should lead to change in behavioural response
- Temporary or permanent removal of all of part of the candidate set of neurons should lead to a measurable perceptual deficit
- What was the Kreiman et al (2000) Nature Neuroscience study lookin at?
How neuronal activity categorize and recognize objects.
- Kreiman et al (2000) Used a number of tests for finding (Category) Selective Neurons state them.
- Activity for the category is different from baseline activity (t-test, Wilcoxon test)
- Differences in activity among categories (ANOVA)
- Differences in activity among pair-wise (selected category vs any category) (Wilcoxon test)
- No differences in activity to distinct individual stimuli within the category (ANOVA)
60.
How is a Responsive Neuron found for a stimulus?
- Activity at task is different than activity at baseline so when it fires differently to the baseline a correlation can be drawn
- Show how many recorded spikes can depict a Neuron (Entorhinal Cortex) coding “Animal” category
- What brain region is used to decipher spatial stimuli?
The Hippocampus
- What brain region was found to be used for Emotional Faces?
The Amygdala
- What do Hippocampal neurons respond to?
Hippocampal neurons respond more to spatial objects
(rat’s hippocampas has ‘place cells’)
- Describe the correlation between perception and imagery.
If a cricket ball is seen a neuron will fire. Then if a person is asked to imagine the ball by an allocated auditory beep the same neuronal will fire.
- Singel Neuron and Visual Imagery:
What three types of neurons did Kreiman et al (2000) Nature show
Three types of neurons
– Visual selective
– Imagery selective
– Both selective
Tight coupling between perception and imagery
Role of medial temporal lobe (MTL) in imagery
67.
Quiroga et al (2005) Nature showed which neuron?
The Jennifer Anderson Neuron -
A remarkable demonstration that a complex concept can be represented at a micro level.
- Invarient visual representation.
- Out of 132 neurons, 51 showed invariance to a particular individual, landmark building, animal or object
- Are these neurons ‘grandmother cells’?
- These cells make link between perception and long-term memory
- Representation is fairly abstract and invariant
- Possibly they are crucial for storing new associations
- ‘One Shot’ Learning (Novelty vs Familiarity)
Rustihauser et al (2006) Neuron
The paper illustrates three spikes what are they?
- Learning Phase
- Recognition: Novel Images
- Recognition: Familiar Image
- MTL neurons have been shown to what ?
- contain information sufficient for reliable novelty- familiarity discrimination
- show rapid plasticity as a result of single trial learning 64
- Spatial Navigation: In search of ‘place cells’
Ekstrom et al (2003) Nature
What area of the brain contains place-responsive cells?
The hippocampus is activated.
Neurons are encoding the space.
- Emotion and Single-Unit Respose
Kawasaki et al (2001) Nature Neuroscience
Draw the 2-D model of Emoition illustrating Aversive Neutral and pleasant firing.
- State the 4 neurons found in Mirror Neurons in Humans.
Mukamel et al (2010) Current Biology
- Same neurons discharge during execution and perception of action
- Overlapping sensory-motor representation
Four types of reported neurons:
- Action-observation neuron
- Action-execution neuron
- Action observation/execution non-matching neuron
- Action observation/execution matching neuron
- Summaize Mukamel et al (2010) mirror neuron findings.
- A significant proportion of neurons in Supplementary Motor Area (SMA), hippocampus responded to both observation and execution of actions
- A subset of neurons demonstrated excitation matching, another subset inhibition matching, and a final subset excitation-inhibition matching
- Existence of multiple systems with neural mirroring mechanisms for flexible integration and differentiation of perceptual and motor aspects of actions performed by self and others
- Pain Perception & Single Neuron
Hutchison et al (1999) Nat Neuroscience
Which neuron is active in pain perception?
ACC neuron encodes (and also mirrors) pain perception
- List 5 clinical applications for single cell recordings.
- Epileptic subjects: Localizing seizure foci
- Depressive/ OCD: Cingulotomy
- Parkinsonian
- Brain-computer-interface
- Neural Prosthetics
- List 9 Limitations & Open Challengesto single cell recordings.
- Only patients can be participants (poor generalizability)
- Total experiment time is limited (usually 1 week)
- Effect of medication
- Heterogeneity of participants (age, cognitive skills, task performance etc)
- Brain areas of study are limited by clinical constraints
- Electrodes cannot be moved
- Number of brain areas to study simultaneously are limited
- Poorly understood spontaneous activity (“resting state”)
- Possibility of microstimulation to the neurons to explore the causal role in perception
