Lecture 1 Single Unit Recording in Humans

Question 1

1. Define Spatial Resolution

Answer 1

The accuracy with which one measures where it is occurring

Question 2

2. Define Temporal Resolution

Answer 2

The accuracy with which one measures when it is occurring

Question 3

3. EEG/ERP(Electroencephalography):

Method type:

Invasivness:

Signal Type:

Answer 3

Method EEG/ERP

Method Type: Recording

Invasiveness: Noninvasive

Signal Type: Electrical

Question 4

4. Single-cell (and multiunit recordings)

Method type:

Invasivness:

Signal Type:

Answer 4

Method Single-cell (and multiunit recordings)

Method Type: Recording

Invasiveness: Invasive

Signal Type: Electrical

Question 5

5. MEG(Magnetoencephalography)

Method type:

Invasivness:

Signal Type:

Answer 5

Method: MEG

Method Type: Recording

Invasiveness: Noninvasive

Signal Type: Magnetic

Question 6

6. TMS(Transcranial magnetic stimulation)

Method type:

Invasivness:

Signal Type:

Answer 6

Method: TMS

Method Type: Stimulation

Invasiveness: Noninvasive

Signal Type: Electromagnetic

Question 7

7. PET(Positron emission tomography)

Method type:

Invasivness:

Signal Type:

Answer 7

Method: PET

Method Type: Recording

Invasiveness: Invasive

Signal Type: Haemodynamic

Question 8

8. fMRI(Functional magnetic resonance imaging)

Method type:

Invasivness:

Signal Type:

Answer 8

Method: PET

Method Type: Recording

Invasiveness: Noninvasive

Signal Type: Haemodynamic

Question 9

9. Draw a visual representation of all the techniques used in neuroimaging with reference to the speed and locolization.

Answer 9

Question 10

10. There are two types of cells in CNS - Glial Cells and neurons: Describe Glial Cells

Answer 10

• More in Number (10-50 X Number of Neurons)
• Supporting neurons
• No direct role in information transmission (?)
• No role in electrical signalling

Question 11

11. There are 2 types of cells in the CNS Glial Cells and Nerve Cells:

Describe Nerve Cells (Neurons)

Answer 11

• 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

Question 12

12. Neurons: name the four morphologically defined regions:

Answer 12

1. Cell Body: Metabolic center, Contains nucleus, genes
2. Dendrites: Receiving signals from other neurons
3. Axons: Carrying signals to other neurons
4. Synaptic Zone: Connection zone between neurons

Question 13

13. Draw the Four Componants of a Neuron:

Answer 13

Question 14

14. Describe the Action Potential:

Answer 14

• 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)

Question 15

15. Action Potentials are __________ (same amplitude)

Answer 15

Action Potential are Nondecremental (same amplitude)

Question 16

16. All-or-nothing phenomenon means..

Answer 16

(either action potential fires at its full amplitude or doesn’t fire at all)

Question 17

17. 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.

Answer 17

Question 18

18. Define Extracellular Recording

Answer 18

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)

Question 19

19. Descibe the process of Extracellular Recording

Answer 19

• A small electrode
• Very high impedance (MΩ)
• Needs special pre-amplifier

Question 20

20. State some issues with extracellular recording

Answer 20

• Mixing of neurons / Unit isolation
• Lack of anatomical details

Question 21

21. Draw a diagram illustrating how extracellular spikes allow the neurons to be found by their amplitude signals.

Answer 21

Question 22

22. Describe Intracellular Recording

Answer 22

• Glass pipette electrode
• Pipette is filled with a solution with similar ionic composition to the intracellular fluid

Question 23

23. What is more useful about the Intracelluar recording compared to extracellular?

Answer 23

• Ideal for recording graded potential leading up to spike discharge or failure of spike discharge in a neuron
• Differentiates excitatory from inhibitory synaptic activity

Question 24

24. What are the issues with Intracellular recording?

Answer 24

Cell damage, Not very feasible in behaving animal

This is not used for humans as it damges cells.

Question 25

25. Draw a diagram of intracellular spikes.

Answer 25

Question 26

26. What are Complex Cells (CC)?

Answer 26

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.

Question 27

27. Draw a Directionally Selective CC illustrating how it is activated.

Answer 27

Question 28

28. Which of the following techniques offer the best spatial resolution? ## Footnote A. fMRI B. EEG C. TMS D. MEG

Answer 28

A. fMRI - can localise the brain regions much better than others.

Question 29

29. Choose the **_incorrect_** statement about Action Potential (AP) ## Footnote 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

Answer 29

Wrong! B The profiles of APs of one neuron can vary depending on the state of the neuron **Action potentials are very similar!!**

Question 30

30. Sample Brief Question: (a) What is an Action Potential (AP) of a neuron?

Answer 30

An action potential is a short-lasting event in which the electrical membranepotential of a cell rapidly rises and falls, following a consistent trajectory.

Question 31

31. Sample Brief Question Briefly describe any four characteristics of AP.

Answer 31

1. As an action potential travels down the axon, there is a change in polarity across the membrane 2. Propagated along the axon at a fixed and slow speed (m/sec) 3. Nondecremental (same amplitude) 4. All-or-None phenomenon (either it fires at its full amplitude or doesn’t fire at all)

Question 32

32. Sample Brief Question ## Footnote What are the major differences between an intracellular and an extracellular recording?

Answer 32

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

Question 33

33. Which recording is more suitable in humans?

Answer 33

Extracellular is far more appropriate as it does not damage the cell body.

Question 34

34. Single Unit recording in Humans: Who are the subjects?

Answer 34

* 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

Question 35

35. Single Unit Recording in Humans: ## Footnote What is the primary target area of the brain?

Answer 35

**MTL (mid temporal lobe)** is the primary target area – Hippoacmapus, Amygdala, Entorhinal cortex, Parahippocampal cortex Average hospital stay = 7-14 days

Question 36

36. List advantages of single cell recording in humans.

Answer 36

* 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

Question 37

37. List the three conditions for selecting a patient / participant for surgery?

Answer 37

1. They must have failed to respond to medical management (antiepileptic drugs) 2. 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. 3. Third, their seizure focus must be localized to a circumscribed portion of the brain that can be safely removed surgically.

Question 38

38. Draw images of the following tools. ## Footnote a) Microelectrode b Hybrid Depth Electrodes c) Strip Electrode d) Research Grid electrode e) Microgrid

Answer 38

Question 39

39. Describe **Acute Recording**

Answer 39

* 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 40

40. Describe Chronic recording

Answer 40

* 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 41

41. What is the procedure for chronic recording?

Answer 41

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

Question 42

42. When are Chronic recording tests carried out?

Answer 42

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

Question 43

43. Neuronal spike recording steps.

Answer 43

1. Amplification (1000-5000) 2. Notch Filtering (50 Hz ± 1 Hz) [60 Hz in USA] 3. High-pass Filter (250-300 Hz) 4. Storage on a PC 5. 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.

Question 44

44. Neuronal Coding: Define Rate Coding

Answer 44

* 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 45

45. Neuronal Coding: Define Temporal Coding

Answer 45

* 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 46

46. Draw an image of a threshold being applied to a neuron firing

Answer 46

Question 47

47. Describe the Spike detection - Neural Cocktail Party Problem

Answer 47

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?

Question 48

48. List some features of neurons that can help to sort the spikes.

Answer 48

Core features: * Loudness - Spike amplitude (∝ 1/Electrode-distance) * Pitch - Spike waveform * Talkative - Firing rate Additional features: * Context - correlation * Modulation of loudness by prosody

Question 49

49. List 4 steps for spike sorting method

Answer 49

Question 50

50. Peri-Stimulus Time Histogram (PSTH) is a simple way to show the neuronal firing pattern list the procedure.

Answer 50

* 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

Question 51

51. Do we need spike sorting?

Answer 51

It can be very useful as seen here where three definite neuronal patterns are sorted.

Question 52

52. What did Quian Quiroga et al (2005) Nature illustrate?

Answer 52

That even when a neuron fires only sporadically it could be down to a specific relationship to a stimulus. Eg. Certain animal visuals.

Question 53

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

Answer 53

B. 20KHz

Question 54

54. Which of the following features is **_not_** used in spike sorting? ## Footnote A.Spike shape B.Spike amplitude C.Firing rate D. Spike’s refractory period

Answer 54

D. Spike’s refractory period This is universal across neurons - 1ms

Question 55

55. What is spike sorting?

Answer 55

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.

Question 56

56. List any three features used in spike sorting.

Answer 56

Amplitude Firing Rate Pitch

Question 57

57. List some links between neurons and perception.

Answer 57

* 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

Question 58

58. What was the Kreiman et al (2000) Nature Neuroscience study lookin at?

Answer 58

How neuronal activity categorize and recognize objects.

Question 59

59. Kreiman et al (2000) Used a number of tests for finding (Category) Selective Neurons state them.

Answer 59

* - 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 60

60. ## Footnote How is a Responsive Neuron found for a stimulus?

Answer 60

- Activity at task is different than activity at baseline so when it fires differently to the baseline a correlation can be drawn

Question 61

61. Show how many recorded spikes can depict a Neuron (Entorhinal Cortex) coding "Animal" category

Answer 61

Question 62

62. What brain region is used to decipher spatial stimuli?

Answer 62

The Hippocampus

Question 63

63. What brain region was found to be used for Emotional Faces?

Answer 63

The Amygdala

Question 64

64. What do Hippocampal neurons respond to?

Answer 64

Hippocampal neurons respond more to spatial objects (rat’s hippocampas has ‘place cells’)

Question 65

65. Describe the correlation between perception and imagery.

Answer 65

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.

Question 66

66. Singel Neuron and Visual Imagery: What three types of neurons did Kreiman et al (2000) Nature show

Answer 66

Three types of neurons – Visual selective – Imagery selective – Both selective Tight coupling between perception and imagery Role of medial temporal lobe (MTL) in imagery

Question 67

67. ## Footnote Quiroga et al (2005) Nature showed which neuron?

Answer 67

The Jennifer Anderson Neuron - A remarkable demonstration that a complex concept can be represented at a micro level.

Question 68

68. Invarient visual representation.

Answer 68

* 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 69

69. ‘One Shot’ Learning (Novelty vs Familiarity) ## Footnote Rustihauser et al (2006) Neuron The paper illustrates three spikes what are they?

Answer 69

1. Learning Phase 2. Recognition: Novel Images 3. Recognition: Familiar Image

Question 70

70. MTL neurons have been shown to what ?

Answer 70

* contain information sufficient for reliable novelty- familiarity discrimination * show rapid plasticity as a result of single trial learning 64

Question 71

71. Spatial Navigation: In search of ‘place cells’ ## Footnote Ekstrom et al (2003) Nature What area of the brain contains place-responsive cells?

Answer 71

The hippocampus is activated. Neurons are encoding the space.

Question 72

72. Emotion and Single-Unit Respose ## Footnote Kawasaki et al (2001) Nature Neuroscience Draw the 2-D model of Emoition illustrating Aversive Neutral and pleasant firing.

Answer 72

Question 73

73. State the 4 neurons found in Mirror Neurons in Humans. ## Footnote Mukamel et al (2010) Current Biology

Answer 73

* Same neurons discharge during execution and perception of action * Overlapping sensory-motor representation Four types of reported neurons: 1. Action-observation neuron 2. Action-execution neuron 3. Action observation/execution non-matching neuron 4. Action observation/execution matching neuron

Question 74

74. Summaize Mukamel et al (2010) mirror neuron findings.

Answer 74

* 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 75

75. Pain Perception & Single Neuron ## Footnote Hutchison et al (1999) Nat Neuroscience Which neuron is active in pain perception?

Answer 75

**ACC neuron** encodes (and also mirrors) pain perception

Question 76

76. List 5 clinical applications for single cell recordings.

Answer 76

1. Epileptic subjects: Localizing seizure foci 2. Depressive/ OCD: Cingulotomy 3. Parkinsonian 4. Brain-computer-interface 5. Neural Prosthetics

Question 77

77. List 9 Limitations & Open Challengesto single cell recordings.

Answer 77

1. Only patients can be participants (poor generalizability) 2. Total experiment time is limited (usually 1 week) 3. Effect of medication 4. Heterogeneity of participants (age, cognitive skills, task performance etc) 5. Brain areas of study are limited by clinical constraints 6. Electrodes cannot be moved 7. Number of brain areas to study simultaneously are limited 8. Poorly understood spontaneous activity (“resting state”) 9. Possibility of microstimulation to the neurons to explore the causal role in perception