Week 6: Methods and limitation of neuroscience

Question 1

The history of methods: 4 major names (case studies)

Answer 1

 Phineas Gage

 Louis Victor Leborgne “Tan” (Patient of Dr. Broca)

 Auguste Deter

 HM

Question 2

Phineas Gage (1848)

Answer 2

 Railroad foreman
 Iron rod driven through his head
 Much of left frontal lobe of brain destroyed

‘the balance between his intellectual faculties and animal propensities seems to have been destroyed’

A good example of where the facts have
become fictionalised
 Story often exaggerated
 He was not aggressive, sexually deviant or a drifter
‘conceived a great fondness for pets, and souvenirs, especially for children, horses and dogs’

Question 3

Auguste Deter

Answer 3

 51-year-old woman from Frankfurt
 progressive cognitive impairment, hallucinations, disorientation, paranoia and psychosocial impairment
 Autopsy revealed arteriosclerotic changes, plaques, neurofibrillary tangles (tangled neurones)
 Her condition was named after her Dr, Alois Alzheimer.

Question 4

Disciplines of the 20th century: Neuropsychology & Medicine

Answer 4

 Neuropsychology – development of behavioural principles

 Medicine – treatments, e.g. brain tumours, epilepsy, schizophrenia

Question 5

20th century: Karl Lashley and ‘Mass action’

Answer 5

 Biological psychologist; found that rats trained to obtain food rewards in mazes retained memories even after progressive brain lesions.
 Concluded that memories were not localised, but distributed throughout the brain
 Developed the principle of ‘mass action’ – amount of memory loss proportionate to the amount of brain tissue loss (experimental method)

Question 6

20th century: Wilder Penfield and the ‘Montreal Procedure’

Answer 6

 Pioneering neurosurgeon: used electrical brain stimulation in awake patients

 Produced ‘vivid memories’, smell, auditory and déjà vu experiences

 Results consistent with localisation of brain function

Question 7

Modern methods:

Answer 7

 Histology
 Experimental ablation
 EEG

 Imaging
	* CT
	* MRI
	* PET
	* fMRI

Question 8

Histology

Answer 8

Visualize particular brain regions
 fixation, sectioning and staining of the brain + observing via microscopy
 identify, quantify and localize cells (e.g. using a particular neurotransmitter or receptor)

Tracing neural connections
 efferent neurons via anterograde labelling
(where are neural pathways going to?)
 afferent neurons via retrograde labelling
(where have neural pathways come from?)
 establish the wiring diagram of the brain

Question 9

Experimental ablation

Answer 9

( The oldest method used in neuroscience, still in common use
 In modern science, typically animal studies)

 Achieved via Stereotaxic surgery
 Brain tissue is destroyed, and alterations in behaviour observed (lesion studies)
* Alterations in brain function are inferred  Allows identification of neural circuits and localisation of behaviour

Question 10

Experimental ablation: How are lesions created?

Answer 10

 (An earlier method) Electrical current using an electrode
* indiscriminate (heat destroys brain tissue)

 Excitotoxic lesions created using injection of excitatory amino acid
	* Destroys cell bodies (spares neural circuitry)

Note: the procedure to allow the creation of lesions (stereotaxic surgery) causes some damage itself, therefore sham lesions must be created in control group before any group comparisons are made

Question 11

Measuring electrical activity

Answer 11

 acute vs. chronically implanted

 using microelectrodes:
	* single-unit recordings based on stereotaxic coordinates

 using macroelectrodes: * scalp recordings e.g. EEG/MEG

Question 12

Imaging: CT scan (Computerised tomography)

Answer 12

• Measures x-rays passed through brain

Question 13

MRI: Magnetic Resonance Imaging

Answer 13

• Measures magnetic field passed through brain

    Brain tissue varies in density, so difference frequencies will be picked up on (=more detail - however MRI is more expensive)

Question 14

Measuring metabolic activity: PET (Positron Emission Tomography)

Answer 14

Utilises radioactive markers to measure metabolic activity

Question 15

Measuring metabolic activity: SPECT (Single positron emission computerised tomography)

Answer 15

• Different radioactive markers
  Marker taken up by brain but not metabolised

(Less expensive, but PET scans result in a better image)

Question 16

Measuring metabolic activity: fMRI (functional magnetic resonance imaging)

Answer 16

• measures oxygen in blood vessels of brain (uses magnetic fields to do this)
• deoxygenated haemoglobin is more magnetic than oxygenated haemoglobin

Areas requiring more energy will have more oxygen taken up, so DETECTS CHANGES IN CEREBRAL BLOODFLOW

Question 17

fMRI, brain and behaviour

Answer 17

can use fMRIs to examine brain activity during psychological tests

 Identify the brain area which ‘lights up’ showing greater blood flow
 Conclude that THAT area is associated with THAT cognitive activity = Localisation

Question 18

Optical Dynamic Laser/Electron Microscopy

Answer 18

▪ Precision images of cellular processes and metabolism
▪ Real Time dynamic images
▪ In-vivo
▪ 3 dimensional images
▪ Limited to animal studies
▪ Extremely time consuming

Question 19

Relative Temporal and Spatial Resolutions (& Invasiveness)

Answer 19

see graph in notes comparing the methods of what they measure and invasiveness.

Question 20

Psychology and the brain

Answer 20

 Brain understood as physical location of psychological phenomena since the late 16th century

 All of psychology (learning, memory, personality, psychomotor performance, motivation, emotion, mental health) is mediated by the brain

Question 21

Measuring neural activity: EEGs electroencephalogram

Answer 21

Brain activity can also be detected by measuring voltage fluctuations within neurons

Other forms of it:
EEG, combined with eye‐movement (electro‐oculogram EOG )
and muscle tension (electromyogram EMG)
measures can be combined to measure sleep - polysomnography (PSG)

Question 22

Polysomnography (PSG): Sleep stages

Answer 22

Combines EEG with EOG and EMG:

Sleep Stages
 Stage N1: drowsiness not quite fully awake.
 Stage N2: ‘true’ sleep, but light (spindles)
 Stages N3: ‘deep sleep’.
 REM: Rapid Eye Movement Sleep

Question 23

PSG: Measures of Sleep (selected)

Answer 23

 Sleep Latency: the time taken to get to sleep (from ‘lights out’ to stage N1)

 Total Sleep: total (N1+N2+N3+R)

(but is PSG better than subjective experience?)

Question 24

PSG v Subjective Experience (Adam, Tomeny and Oswald, 1986)

Answer 24

people over‐estimate Sleep Latency (we think it takes longer to get to sleep than it really does)

people underestimate Total Sleep Time (we think our sleep is shorter than it really is)

Question 25

Borkovec et al (1981): Method

Answer 25

 Compared the sleep of 25 insomniacs and 10 good sleepers
 Each woken up in the 5th minute of first episode of Stage 2 (N2)
 Asked “were you awake or asleep?”
 Most good sleepers said “asleep”; most insomniacs said “awake”

Question 26

Borkovec et al (1981): findings

Answer 26

Despite identical electrophysiology, people “experience” their sleep differently

Sleep onset is an experiential, as well as an electrophysiological phenomenon

Question 27

Experience matters: Neuroscience leaves gaps…

Answer 27

• Intelligence
  * Inter-personal relationships
  * Mental illness
  * Consciousness

 Is knowledge of neural activity always relevant?
 Brain activity is indisputably occurring, but what does this do to explain experiential elements?

Question 28

The brain and the mind

Answer 28

the problem of mind and body (consciousness) remains unresolved – even in the context of neuroscience

David Chalmers – conscious experience may represent a limit of science (see workshop)

Question 29

The problem with objective measurement

Answer 29

 Neuroscience is founded on objective measurement
 Much of psychology is concerned with people’s experience:
* Mental illness
* Motivation
 Objective measures of experiential factors are not possible.

 Psychological science will continue to develop alongside neuroscience

 There remains more to ‘psychology’ than brain function

Question 30

Reading: Radio frequency lesion

Answer 30

destroys brain tissue near the tip of electrode

destroys cell bodies, axons and terminals in the region of the electrode

Question 31

Reading: Excitotoxic lesion

Answer 31

• uses excitatory amino acid (such as kainic acid) (it overstimulates the neurones to death)
• destroys only cell bodies near tip of cannula; spares axons passing through the region

Inevitable damage to the brain when inseting the cannula (and for both methods really) = important to use a sham lesion (insert an empty cannula) in control condition.

Question 32

Reading: Infusion of local anesthetic/ drug that produces local neural inhibition

Answer 32

Temporarily inactivates a specific brain region

Temporary = animals can serve as its own control

Question 33

Stereotaxic surgery

Answer 33

Aims to place an electrode or cannula in a specific region within the brain

Consult stereotaxic atlas for coordinates

Question 34

Reading: Method to find the location of a lesion in a dead brain

Answer 34

perfuse brain, fix brain, slice brain, stain sections

Question 35

Reading: method to find location of lesion in a living human

Answer 35

CT scan (uses x-rays)

MRI scan (uses magnetic field and radio waves - better image but more expensive)

Question 36

Reading: Confocal laser scanning microscopy

Answer 36

visualise details in thick sections of tissue

Can be used to see ‘slices’ of tissue in living brain; requires the presence of fluorescent molecules in the tissue

Question 37

Reading: Microelectrodes

Answer 37

record electrical activity of single neurones

can be implanted permanently to record neural activity as animal moves

Question 38

Reading: Macroelectrodes

Answer 38

Record electrical activity of regions in the brain

in humans, usually attached to the scalp with a special paste

Question 39

reading: methods recording metabolic activity

Answer 39

PET scan

fMRI

SPECT

Question 40

Reading: Deep brain stimulation

Answer 40

A technique using stereotaxic surgery to implant a permanent electrode in the brain; used to treat chronic pain, movement disorders, epilepsy, depression, and obsessive-compulsive disorder.

Question 41

Histological methods: verifying a lesion in animals process

Answer 41

must fix, slice, stain, and examine the brain

• Fixation & sectioning:
  Fixative - A chemical such as formalin; used to prepare and preserve body tissue.
  Microtome - An instrument that produces very thin slices of body tissues.
  Cryostat - An instrument that produces very thin slices of body tissue inside a freezer chamber.
• staining
  Methylene blue and cresyl violet are two examples of dyes that stain cell bodies
  • Electron microscopy: Transmission electron microscope, scanning electron microscope
  • Confocal laser scanning microscopy
    • Immunocytochemical method - A histological method that uses radioactive antibodies or antibodies bound with a dye molecule to indicate the presence of particular proteins of peptides.

Question 42

2 tracing methods: (to understand direction of neural pathway)

Answer 42

Anterograde tracing method: labels the axons and terminal buttons of neurons whose cell bodies are located in a particular region

Retrograde tracing method: employ chemicals that are taken up by terminal buttons and carried backward through the axons toward the cell bodies

Question 43

Reading: How to identify small fibre bundles

Answer 43

(not visible by MRI)

Use Diffusion tensor imaging (DTI)
—> An imaging method that uses a modified MRI scanner to reveal bundles of myelinated axons in the living human brain.

Question 44

Reading: MEG - Magnetoencephalograph

Answer 44

calculate the source of particular signals in the brain.
○ These devices can be used clinically—for example, to find the sources of seizures so that they can be removed surgically
○ An important advantage of magnetoencephalography is its ability to show changes in brain activity relatively quickly.

(fMRI won’t detect brain changes as quickly as MEG)

Question 45

Reading: disadvantages of PET scan

Answer 45

PET scanners is they are costly to operate

the relatively poor spatial resolution (the blurriness)

Short-lived events within the brain are likely to be missed.

Uses radioactive tracer

Question 46

Reading: microdialysis

Answer 46

To measure the amount of neurotransmitter released in particular regions of the brain

A procedure for analysing chemicals present in the interstitial fluid by extracting them through a small piece of tubing made of a semipermeable membrane that is implanted in the brain