Week 6: Methods and limitation of neuroscience Flashcards
The history of methods: 4 major names (case studies)
Phineas Gage
Louis Victor Leborgne “Tan” (Patient of Dr. Broca) Auguste Deter
HM
Phineas Gage (1848)
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’
Auguste Deter
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.
Disciplines of the 20th century: Neuropsychology & Medicine
Neuropsychology – development of behavioural principles
Medicine – treatments, e.g. brain tumours, epilepsy, schizophrenia
20th century: Karl Lashley and ‘Mass action’
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)
20th century: Wilder Penfield and the ‘Montreal Procedure’
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
Modern methods:
Histology
Experimental ablation
EEG
Imaging * CT * MRI * PET * fMRI
Histology
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
Experimental ablation
( 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
Experimental ablation: How are lesions created?
(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
Measuring electrical activity
acute vs. chronically implanted
using microelectrodes: * single-unit recordings based on stereotaxic coordinates using macroelectrodes: * scalp recordings e.g. EEG/MEG
Imaging: CT scan (Computerised tomography)
- Measures x-rays passed through brain
MRI: Magnetic Resonance Imaging
- 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)
Measuring metabolic activity: PET (Positron Emission Tomography)
Utilises radioactive markers to measure metabolic activity
Measuring metabolic activity: SPECT (Single positron emission computerised tomography)
- Different radioactive markers
Marker taken up by brain but not metabolised
(Less expensive, but PET scans result in a better image)
Measuring metabolic activity: fMRI (functional magnetic resonance imaging)
- 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
fMRI, brain and behaviour
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
Optical Dynamic Laser/Electron Microscopy
▪ Precision images of cellular processes and metabolism
▪ Real Time dynamic images
▪ In-vivo
▪ 3 dimensional images
▪ Limited to animal studies
▪ Extremely time consuming
Relative Temporal and Spatial Resolutions (& Invasiveness)
see graph in notes comparing the methods of what they measure and invasiveness.
Psychology and the brain
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
Measuring neural activity: EEGs electroencephalogram
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)
Polysomnography (PSG): Sleep stages
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
PSG: Measures of Sleep (selected)
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?)
PSG v Subjective Experience (Adam, Tomeny and Oswald, 1986)
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)
Borkovec et al (1981): Method
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”
Borkovec et al (1981): findings
Despite identical electrophysiology, people “experience” their sleep differently
Sleep onset is an experiential, as well as an electrophysiological phenomenon
Experience matters: Neuroscience leaves gaps…
- 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?
The brain and the mind
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)
The problem with objective measurement
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
Reading: Radio frequency lesion
destroys brain tissue near the tip of electrode
destroys cell bodies, axons and terminals in the region of the electrode
Reading: Excitotoxic lesion
- 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.
Reading: Infusion of local anesthetic/ drug that produces local neural inhibition
Temporarily inactivates a specific brain region
Temporary = animals can serve as its own control
Stereotaxic surgery
Aims to place an electrode or cannula in a specific region within the brain
Consult stereotaxic atlas for coordinates
Reading: Method to find the location of a lesion in a dead brain
perfuse brain, fix brain, slice brain, stain sections
Reading: method to find location of lesion in a living human
CT scan (uses x-rays)
MRI scan (uses magnetic field and radio waves - better image but more expensive)
Reading: Confocal laser scanning microscopy
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
Reading: Microelectrodes
record electrical activity of single neurones
can be implanted permanently to record neural activity as animal moves
Reading: Macroelectrodes
Record electrical activity of regions in the brain
in humans, usually attached to the scalp with a special paste
reading: methods recording metabolic activity
PET scan
fMRI
SPECT
Reading: Deep brain stimulation
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.
Histological methods: verifying a lesion in animals process
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.
2 tracing methods: (to understand direction of neural pathway)
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
Reading: How to identify small fibre bundles
(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.
Reading: MEG - Magnetoencephalograph
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)
Reading: disadvantages of PET scan
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
Reading: microdialysis
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