Single-Cell

Question 1

what are the two types of single - cell recording schemes?

Answer 1

intracellular and extracellular

Question 2

extracellular electrode is what size? …

Answer 2

small electrode less than 10 microns !
LOCAL SCALE
plunged in to tissue by neurosurgeons

Question 3

extracellular electrode has a very XXX xxxx

Answer 3

Very high impedance (M) resists the flow of current

Needs special pre-amplifier to get over this

Question 4

what are the issues with extracellular?

Answer 4

1) Mixing of neurons (signal from other cells picked up - need spike sorting)
2) Unit isolation
3) Lack of anatomical details

Question 5

intracellular electrode is …

Answer 5

Glass pipette electrode (<1 micron) is inserted inside the cell membrane

Question 6

what is the pipette filled with?

Answer 6

Pipette is filled with a solution with similar ionic composition to the intracellular fluid

Question 7

what is benefit of intracellular recording?

Answer 7

Ideal for recording graded potential leading up to spike discharge or failure of spike discharge in a neuron

Extra has no information here

Question 8

And what can intracellular discriminate?

Answer 8

Differentiates excitatory from inhibitory synaptic activity

Question 9

what are the issues with intracellular?

Answer 9

1) Cell damage

2) Not very feasible in behaving animal (invasive)

Question 10

what are Complex Cells (CC) ?

Answer 10

respond to specific orientation / movement

directionally selective

Question 11

Complex Cells are located in? and were found by?

Answer 11

first noted in V1 by Hubel DH, Wiesel T (1962)

Question 12

other key cells discovered through single cell?

Answer 12

Hierarchical Information Processing
Mirror Neuron
Multisensory Neuron
Place Cells

Question 13

Choose the correct statement about Action Potential (AP)

Answer 13

A. AP fire with varying degrees of input stimulation
B. The profiles of APs of one neuron can not vary depending on the state of the neuron
C. AP propagates in a decremental fashion
D. The duration of AP is approx. 2 ms

Question 14

single cell recordings in humans are only taken from

Answer 14

medical patients with pharmacologically resistant epilepsy

MTL (mid temporal lobe) is the primary target area
– Hippoacmapus, Amygdala, Entorhinal cortex, Parahippocampal cortex

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

Average hospital stay = 7-14 days

Question 15

what is their treatment ?

Answer 15

Electrodes are surgically implanted to localize the focus of the seizures

Treatment Removal of brain tissues generating seizures

Question 16

What are the 5 main Advantages of Single Unit Recording in Humans?

Answer 16

1) Signal source: Direct recording
2) Spatial resolution: 1-2 mm (EEG ~ cm)
3) Temporal resolution: ~ ms
4) Signal-to-noise ratio: (less artefacts, i.e. no blink artefacts)
5) High frequency brain activity

Question 17

Acute Recording is ? and USES WHICH ELECTRODE ?

Answer 17

critical to do immediately - > No requirement of preoperative diagnostic testing.

no time - done quickly

microelectrode

always conscious - to communicate if the tissue being removed has no sig imput - minimal impact of removed tissue

Question 18

details of an acute recording?

Answer 18

> 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)

Question 19

What is chronic recording?

Answer 19

more common

when unsure of location

• 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

Question 20

what is MRI used for in single-cell?

Answer 20

locating exactly where electrodes are placed

• Pre- and post- MRI scans are necessary to localize electrodes

Question 21

In chronic recording, the patient is often tired, why?

Answer 21

– Doctors need patients to have fits to discover where they come from.
– Usually antileptic medication is lowered to increase the chance of epilepsy
– If no seizure is recorded, patient is often sleep deprived

fits keep peeps up at night

Question 22

In chronic recording, tests at two points are required… why?

Answer 22

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

Question 23

when is chronic testing done?

Answer 23

• 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

Question 24

What are the 3 main practical/technique steps of single -cell recording?

Answer 24

1) Amplification (1000-5000)
2) Notch Filtering (50 Hz ± 1 Hz) [60 Hz in USA]
3) High-pass Filter (250-300 Hz)

Question 25

What si the common sampling frequency of single-cell?

Answer 25

~ 20 kHz (high frequency data, so high sampling rate) 0.05 every millisecond

Question 26

what two kinds of recording style are there?

Answer 26

``` Continuous Signal Discrete signal (signal > threshold) ```

Question 27

What are the two types of neuronal coding?

Answer 27

rate | temporal

Question 28

what is rate coding ?

Answer 28

Number of action potential – 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

Question 29

what is temporal coding ?

Answer 29

– 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)

Question 30

what is spike detection and sorting?

Answer 30

detecting signal from noise separating signal from an intended neuron, against a neighboring neuron or group of neurons Spike Sorting – Neural Cocktail Party Problem

Question 31

core features of spike?

Answer 31

Spike amplitude Spike waveform Firing rate Additional features: Context Correlational function Modulation of loudness by prosody

Question 32

spike sorting techniques ?

Answer 32

``` Raw data filtered data spike detection feature extraction clustering ``` ``` Misc. spike sorting method: PCA based (principal components) ICA based (independent components) Other classifiers ```

Question 33

how do we usually display single - cell?

Answer 33

Peri-Stimulus Time Histogram (PSTH) * Align spike sequences with stimulus onset (or any event) which repeated n times * Divide the stimulus period S into N bins of size D * Count the number of spikes (ki) within individual bin for all trials * Compute the histogram Basically counting how many times it fires in response to an event

Question 34

``` The typical sampling frequency used for recording single neuron activity is A. 2KHz B. 20 KHz C. 200 KHz D. 200 Hz ```

Answer 34

B. 20 KHz

Question 35

Which of the following features is not used in spike sorting?. Spike shape Spike amplitude Firing rate

Answer 35

well all of them. unclear actually (i emailed joy) possibly they were looking for all

Question 36

Which of the following features is not used in spike sorting?. Spike shape Spike amplitude Firing rate

Answer 36

well all of them. unclear actually (i emailed joy) possibly they were looking for all

Question 37

Neurons should have discernible statistical differences....

Answer 37

in their firing patterns in response to the different external stimuli

Question 38

what is a Responsive Neuron?

Answer 38

- Activity at task is different than activity at baseline

Question 39

what is a (Category) Selective Neuron

Answer 39

Activity for the category is different from baseline activity - 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)

Question 40

example of a category neuron / Single Neuron & Object Recognition

Answer 40

1) Famous face neuron in hippocampus 2) Spatial encoding hippocampi = place cells in rats and taxi drivers from hugo spiers 3) Entorhinal Cortex coding ‘Animal’ Category

Question 41

what about difference between perception and imaginary ?

Answer 41

Kreiman et al (2000) = Correlation between Perception & Imagery • Three types of neurons – Visual selective – Imagery selective – Both selective • Tight coupling between perception and imagery • Role of MTL in imagery

Question 42

what is Visual Invariance?

Answer 42

Quiroga et al (2005) 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

Question 43

what is one-shot learning ?

Answer 43

Rustihauser et al (2006) MTL neurons • contain information sufficient for reliable novelty- familiarity discrimination • show rapid plasticity as a result of single trial learning sequences of faces - new face or old face?

Question 44

Emotion & Single-Unit Response

Answer 44

Kawasaki et al (2001) Emotion Processing by PFC Neurons

Question 45

‘Mirror Neuron’ in Humans

Answer 45

Mukamel et al (2010) Current Biology * 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

Question 46

Clinical applications of single-cell?

Answer 46

* Epileptic subjects: Localizing seizure foci * Depressive/ OCD: Cingulotomy * Parkinsonian * Brain-computer-interface * Neural Prosthetics

Question 47

Limitations & Open Challenges

Answer 47

* 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

Question 48

in comparison to other techiniques, single-cell offers...

Answer 48

Single-neuron recording offers the best temporal and spatial resolutions A diverse range of brain functions are represented by the activities at micro (neuronal) level but * But only patients can be the participants * Recording is very invasive and complex