Lecture 5 - How to study the brain Flashcards
Stroke
Often causes motor and language deficits
Alzheimer’s disease
Degeneration later on, damage begins in medial temporal lobe which affects hippocampus and surrounding areas (memory deficits)
Parkinson’s disease
Diminished substantia nigra, motor deficits (difficulty initiating movement), dopamine release in basal ganglia is important in initiating movement
What do these neurological diseases show?
How better understanding of neurological cause of these diseases can help treatments
Patient Leborgne ‘Tan’
Stroke resulted in damage in left frontal cortex, leading to specific speech production deficits e.g. could only say ‘tan’. Led to knowledge that Broca’s area is important for speech production
Phineas Gage
Iron rod through frontal cortex (survived) – personality and behaviour changed, suggesting these regions at the front of the brain hold the key to personality
Patient HM
Suffered from epilepsy and underwent temporal lobe resection (involve hippocampus and surrounding lobe) – specific memory impairments but otherwise psychologically normal
What do these case studies and diseases show?
- Highlight that brain areas are key to aspects of our psychological experience
- Specific brain areas have specific roles
Behavioural studies of neurological patients/particular brain damage
Understand what is damaged gives an idea of what that area’s role is in behaviour. Often limited because damage is never complete, and patients have other conditions
Manipulations of brain function
Examining how that impacts function of interest (ethics – animal studies)
Neuroanatomy and histology
E.g. structure and function, connection to other brain areas
Electrophysiology
Listening in to electrical activity of neurons while subject performs a function
Imaging (MRI and PET)
Look at structure/function without damaging patient
Computational models/brain-based devices
Once we have a reasonable understanding of brain regions link to behaviour/cognitions, we can build models and test whether theories/ideas are really working
Multi-disciplinary
Understanding of brain-behaviour relations requires combination of many different methodological approaches
Animal studies
Reveal causal relationships e.g. rat brain and human brain have similar brain regions/constituents, and they are similarly wired
Patient H.M
- Henry G. Molaison (1926-2008)
- Surgical resection of medial temporal lobe, mainly hippocampus, to stop epileptic seizures
- Thorough behavioural and cognitive analysis:
- Striking impairments in specific types of memory, including aspects of declarative (memory we can declare/talk about/consciously recollect, includes semantic memory and episodic memory) and spatial memory (memory of locations/directions)
- Other cognitive and memory functions were largely unaffected
- Corkin (2002)
- Led to the concept of memory systems
- Memory is not a unitary construct, but we have distinct types of memory which rely on distinct brain areas
- Milner et al. (1998)
Experimentally induced lesions and other brain manipulations (hippocampus example)
- Selective destruction of specific brain sites (mechanical, electrolytic, neurotoxic)
- Temporary pharmacological manipulations via pre-implanted micro-cannulae to switch neurons or specific receptors on and off
- Electrical stimulation of specific brain sites
- E.g. stereotactic brain surgery in anaesthetized rats
- Targeted mutations of brain-specific genes (possible in mice)
- Optogenetics – manipulate specific neurons in the brain genetically so that they become light sensitive, then by shining a quick light, you can inhibit or excite neurons
- In humans, trans-cranial magnetic stimulation (TMS) – disrupt electrical activity of neurons by inducing a magnetic field. Limited spatial resolution and can only be used on surface (cortical) regions
- Functional ultrasound stimulation in development (could target deeper brain areas)
- To study deep brain areas, generally need animal studies
Selective place learning deficits after hippocampal lesions in rats
- Watermaze – used to measure spatial memory in rodents – have to find escape flaps/platforms using spatial cues arranged around the pool
- More often they do it, better spatial memory
- Can also remove escape platform
- Measure rats paths and how long they take etc.
- RGM Morris et al. (1982)
- Hippocampal lesion
- Control group had more crossings over target region than over other areas of water pool
- Specifically hippocampal lesions impair spatial learning
- The study suggests that the hippocampus is necessary for spatial and declarative memory
Neuronal tract tracing
- PHA-L is injected into a region of the brain and taken up by dendrites and cell bodies
- Compound travels along neuronal direction (either in direction of action potential or not)
- PHA-L is transported by axoplasmic flow
- Axons and terminal buttons can be seen under the microscope
- Gives understanding of neuronal connections between brain regions
Diffusion magnetic resonance imaging (Berg-Johansen & Rushworth, 2009)
- Used for humans
- Highlight white fibre tracts and main regions in the human living brain
- Lower spatial resolution
Polymodal sensory input to the hippocampus (Burwell, 2000)
- What the hippocampus is connected to
- Lines in model show strength of connections from hippocampus to other brain regions
- Hippocampus connected to all other sensory cortices (info funnelled into hippocampus to give us the capability to form memories)
Electrophysiology (hippocampus example)
- Recording the electrical activity of the brain
- Implant electrodes in rat brain to record electrical signals from within the brain
- Single-unit recordings: recording the electrical activity (action potentials) of single neurons
- E.g. ‘place cells’ in the hippocampus – neurons that fire only if the animal is in a particular region/location. Neurons code for specific places. Useful for forming spatial memories
- Local field potential (LFP) recordings = recording electrical potentials generated by many neurons (‘field potentials’)
- Certain behavioural states are characterised by different field potentials in hippocampus e.g. discriminate different phases of sleep
- E.g. LFP recorded from rat hippocampus
Electrophysiology in humans
- Invasive single-unit and LFP recordings = only conducted in rare cases for the pre-surgical evaluation of epilepsy patients (Engel et al., 2005)
- Surface EEG = spontaneous and event-related (evoked)
- Record electrical activity in brain by putting electrodes on the scalp
- See different activity e.g. theta activity
- Magnetencephalography (MEG) = measures the small magnetic-field changes accompanying electrical voltage due to brain activity
- Better spatial resolution than EEG (<1cm)
- New wearable MEG scanner developed in Nottingham
