What are some of the reasons for brain intervention?
1. Experiments to explore science of the brain
2. Patients with brain diseases require treatment
3. People with normal brain function wish to alter function/for pleasure
Lesions are helpful because they can attribute direct causes to difference in behaviour because it permits what? However, why is it often difficult realistically?
because they permit 'before and after' measurement (of behaviour)
However, lesions in humans are often accidental and even lesions in surgery may not be useful for experimental purposes because the behaviour before is not properly documented.
(Animal lesions are therefore useful).
Who is Phineas Gage and what can you tell me about him?
He had accidental damage to the left prefrontal cortex, which apparently caused him to be 'no longer Gage'.
However, the evidence is more anecdotal (especially for his personality before the accident).
Give a famous example of deliberate brain damage.
Henry Molaison (patient HM)
had bilateral medial temporal lobectomy (damaging hippocampus, amygdala and temporal cortical regions.)
to alleviate seizures
Profound anterograde amnesia
and graded retrograde amnesia.
Well-documented and has helped understand processes underlying memory formation and retention.
What has ablative surgery been used to treat?
(Although reversible Deep Brain Stimulation is now preferred.)
Name 2 methods of lesions.
Radio frequency lesions: electrodes inserted into brain and a high-frequency current is applied to brain tissue. Produces heat that kills surrounding cells - non-specific.
Excitotoxic lesions: excitatory amino acid injected into brain and this overstimulates the neuron causing cell death. Only kills target neuron cell bodies.
What is TMS used for?
To measure aactivity and function of certain brain regions in humans. Localised to small regions (5-30mm) of cortex, but cannot penetrate deep into brain.
To treat major depression.
How does deep brain stimulation work?
Surgical implantation of electrode deep into brain
Programmable pulse generator (brain pacemaker) and battery under skin by collar bone
Electrode delivers impulses to specific target brain regions.
What is DBS used to treat?
Shows promise for depression and Tourette's syndrome
Which brain regions are often targeted by DBS? (Give for different conditions.)
Usually within the Basal Ganglia
Parkinson's and dystonia: either globus pallidus or subthalamic nucleus
Essential tremor: ventrointermediate nucleus of the the thalamus
Non-approved experimental treatments for depression: Brodmann Area 25
Obsessive compulsive: ventral striatum
What can you say about the precise mechanism by which DBS works?
It is not yet fully understood.
COuld be that the target regions may be overactive in these disorders
DBS msy trfuvr activity of these target regions, normalising the function of the previously-overactive brain circuits.
What is the name of the method that is often the last line of intervention in treatment of major depressive disorder and other illness? Tell me a bit about it.
Electroconvulsive therapy (ECT)
For major depressive disorder, schizophrenia, mania and severe obsessive compulsive disorder.
Probably changes baseline chemistry and activity within the brain but not fully understood.
Patients have reported of retrograde and anterograde amnesia following ECT.
List 3 ways in which we can interfere with neurotransmitter signalling.
Decrease amount of neurotransmitter released into synapse
Increase amount of neurotransmitter active in synapse by blocking reuptake of neurotransmitter back into the pre-synaptic terminal.
Change balance of action of a neurotransmitter at different types of receptor.
List some drugs that affect neurotransmitter function in the brain.
Opioid: Similar effect to natural opiod-like neurotransmitters like endorphins; decreased alertness and respiration.
Cocaine: triple reuptake inhibitor (TRI). Affects reuptake of dopamine, serotonin and norepinephrine. Creates euphoria. Acts on brain's 'reward pathway', making it addictive.
Abused drugs often affect dopamine levels in the nuclear accumbens.
List 4(+1) ways drugs can change the action of neurotransmitters in synapses. (on the website) Give examples. IMPORTANT CARD.
1. Mimic neurotransmitters - Opioid drugs like heroin. Mimics action of natural neurotransmitters like endorphin. However, heroin acts on more receptors so the effect is greater.
2. Blocking reuptake of neurotransmitter - Eg1. Prozac (anti-depressant drug - selective serotonin reuptake inhibitor SSRI). Eg2. Cocaine(binds to dopamine transporter that facilitates the reuptake of dopamine to the pre-synaptric neuron.
Eg 3. Methylphenidate (eg Ritalin - NET/DAT inhibitor - used for treatment of ADHD).
3. Increase sensitivity of post-synaptic neuron to a particular neurotransmitter. Benzodiazepines' relaxation effects result from this increased sensitivity to GABA's inhibitory impact on cellular activity.
4. Receptor-specific drugs. More recently, drugs that specifically target certain sub-types of receptor (such as blocking dopamine D2 receptors) have been looked into, esp as there are precise forms of brain impairment caused by failure/over-activity of a specific receptor sub-type. Most, like methylphenidates (Ritalin) affect multiple target receptors - like dopamine and noradrenaline transporters for Ritalin.
5. [Not to do with drugs, but] diet can affect neurotransmitter availability as well.
Describe a way in which diet can be manipulated to alter neurotransmitter function.
ATD examines the consequences of an acute decrease in 5-HT (serotonin) produced by a reduction in brain levels of its precursor, tryptophan (TRP).
Why is studying the effects of serotonin reduction in the brain important?
To understand the importance of selective serotonin reuptake inhibitors (SSRI) such as Prozac to treat disorders such as anxiety, depression and OCD.
Tryptophan is an __ amino acid and a member of the group __ __ __ __ (__). In order for the brain to be able to make __, __ must be present in the __ and must be able to be transported across the __-__ __.
large neutral amino acid (LNAA) [tyrosine, which is one ingredient for dopamine, is also an LNAA]
What is the method of acute tryptophan depletion (ATD)?
Ingesting an amino acid mixture that lacks TRP but contains large number of other LNAAs (eg. valine, tyrosine).
Increase in amino acids in blood plasma stimulates liver to synthesise protein, removing amino acids (including TRP) from blood.
Non-TRP LNAAs also compete for the carrier that transports LNAA across blood-brain barrier.
Therefore, less TRP is in brain, and less serotonin synthesis. [TRP at minimum level after 5-7hrs of ingestion].
Remind me again how serotonin is produced.
TRP is converted to 5-HTP by TRP hydroxylase
Then carboxylated by aromatic acid decarboxylase to 5-HT.
What has been the general findings in these ATD studies?
That there is no straightforward link between serotonin depletion and the emergence of symptoms,
suggesting that these disorders are not caused simply by a decrease in serotonin in the brain.
Although it did change slightly during Ultimatum Game (ATD produced people who rejected unfair offers more).
Can a similar thing to ATD be done for a different neurotransmitter? Which one?
Can be reduced in similar way by ingesting amino acid mixture that is lacking tyrosine and phenylalanine.
Low dopamine __ receptor availability in the __ correlates with what?
correlates with poor stopping ability (for car scenario) in human volunteers.
[Should be said that D2 receptor activity related to Cocaine addiction - increases dopamine release in striatum - more 'glow' on the MRI]
Give the name of the corresponding monoamine transporters that regulate the levels of neurotransmitter in the synapse (for dopamine, noradrenaline, serotonin).
Dopamine - DAT
Noradrenaline - NET
Serotonin - SERT
List 3 personality/behaviour assessment questionnaires.
Barratt Impulsiveness Scale
Big Five Personality Test
Beck Depression Inventory
What is the cause of Parkinson's? (Imagine a diagram too).
Denervation of dopaminergic neurons in the Substantia Nigra.
Loss of dopamine in striatum.
List some cognitive tests.
CANTAB (Cambridge Neuropsychological Test Automated Battery) - testing such things as working memory and attention.
Kohs block for intelligence
Dopamine, serotonin and noradrenaline. Give broad simple roles of each.
Dopamine: Reward (motivation); Pleasure; Euphoria; Motor function; Compulsion; Perseveration