Lecture 8

Question 1

What is the Basal ganglia?

Answer 1

“Old system”

exerts influence on motor and prefrontal areas via thalamus

exerts influence on limbic circuits

can be thought as filtering our actions ready for execution

Question 2

What is the basal ganglia made up of?

Answer 2

Striatum

Globus pallidus
- interna (GPi)
- externa (GPe)

Subthalamic nucleus (STN)

Substantia nigra

Question 3

What is the striatum and where is it located?

Answer 3

Input structure of the basal ganglia - where the cortex generally projects through and where info from the cortex enters the basal ganglia

Question 4

where does the subthalamic nucleus (STN) sit?

Answer 4

below the thalamic nucleus
(look at notes for diagram)

Question 5

what is the direct pathway information travels from the cortex to the thalamus?

Answer 5

net excitatory and its connection back to the cortex excites the motor cortex, which helps to select the motor plan for execution

the activity travels from the cortex to the striatum, down to the GPi which then passes it onto the thalamus and back to the cortex which sends it to the spinal cord

Question 6

what is the indirect pathway information travels from the cortex to the thalamus?

Answer 6

net inhibitory so its connections back to the cortex will suppress a given motor plan and through a balance of excitation and inhibition, one motor plan will ultimately be selected over all others and will eventually be executed

cortex -> striatum -> GPe -> STN -> GPi -> thalamus -> cortex -> spinal cord

Question 7

what are the two dopamine receptors?

Answer 7

D1 receptors, they are excited by dopamine and they innervate the direct pathway

D2 receptors are inhibited by dopamine and they directly innervate the indirect pathway

Question 8

describe the role of dopamine

Answer 8

Most plans in the cortex will excite the striatum, but the balance of activity in the direct and indirect pathway is regulated by a small structure on the brainstem called the substantia nigra

draw the diagram

Question 9

how can you identify neuronal loss in substantia nigra pars compacta (SNc) visually?

Answer 9

Dark pigmentation of the substantia nigra is lost when diagnosed with parkinson’s disease

With this cell loss, these patients also lose the dopaminergic innovation to the striatum

Question 10

how can you identify loss of striatal dopamine visually?

Answer 10

reduced colour and size of activity in radiopharmaceutical imaging as see in parkinsons patients

asymmetric loss of uptake of the tracer

Question 11

what occurs due to a weak direct pathway in the brain?

Answer 11

akinesia

When cells in the SN die, the dopaminergic innovation to the striatum is lost and this is severely imbalanced, this whole basal ganglia sets itself up

Since the loss of dopamine no longer drives the direct pathway and it no longer inhibits the indirect pathway, this leads to too little facilitation of multiple programs that are sent from the cortex and at the same time imposing too much inhibition of those motor programs that the brain is trying to select

Action plans are no longer able to be selected efficiently, and those that are selected end up. Being slow and unrefined because of excessive inhibition from the indirect pathway

Question 12

what is parkinsons disease?

Answer 12

Degeneration of dopamine neurons in substantia nigra

Neurological / psychiatric disease caused (largely) by alteration in a single neurochemical – dopamine

Disordered signals sent to SMA: motor disorder

Also influences limbic system: motivation and emotional disturbance

Question 13

name the three cardinal symptoms of PD

Answer 13

1. Absence/slowness of movement (akinesia/bradykinesia)
2. Stiffness or rigidity
3. Tremor “at rest” (much reduced with active movement)

Question 14

name at least 4 other major symptoms

Answer 14

1. Gait and postural disturbances
2. Depression
3. Speech and swallowing problems
4. Mental confusion
5. Sleep disturbances
6. Loss of sense of smell

Question 15

what are the three main treatments for Parkinson’s disease?

Answer 15

• Levodopa (L-DOPA: a precursor for dopamine)
  a drug that can be administered
• Transplants
  
  • Bone marrow derived stem cells
  • Embryonic stem cells
  • (Adult brain cells)
• Neuro-surgery to rebalance connections between striatum and SMA
  
  • Thalamotomy
  • Pallidotomy
    *Deep brain stimulation

Question 16

in which way does long term L-DOPA tilt the balance of direct/indirect?

Answer 16

back towards direct

Question 17

explain the long term L-DOPA outcome

Answer 17

Too much dopamine can push the balance of the basal ganglia circuits too far towards the direct pathway

This lead to premature selection of action and even uncontrolled selection of inappropriate actions that have not been properly suppressed

Question 18

what three conditions experience a loss of striatal neurons (STN)?

Answer 18

· Huntingdon’s
· Hemiballism
· Tourette’s

Question 19

what are chorea form movements?

Answer 19

involuntary irregular jerky movements

Question 20

summarise the basal ganglia

Answer 20

· The basal ganglia form a series of loops between cortex, striatum, pallidum, back to cortex via thalamus

· Function to serve action selection

· Circuit relies on dopamine

· Strong links to common neurological conditions

Question 21

what are the four cortical-basal ganglia loops?

Answer 21

motor

occulomotor

executive/associative

emotion/motivation

Question 22

how is the basal ganglia and eye movement related?

Answer 22

Basal ganglia act as “filter” to add contextual information onto reflex control of eye movements – generalized inhibition of the sup. colliculus except for target of interest

(refer to diagram in notes)

Question 23

what is the function of the basal ganglia?

Answer 23

· Acts as a filter/selector with broad cortical input and motor output (whilst also suppressing particular outcomes)

· Inputs: sensory-motor, limbic and cognitive

· Outputs: excitatory and inhibitory modulation of thalamus, modulation of cortical state (esp. SMA)

· Selection of appropriate behaviours?

· Self-initiation of behaviours

Question 24

what learning system occurs in the cortex?

Answer 24

learning relationships

Question 25

what learning system occurs in the basal ganglia?

Answer 25

reinforcement learning

Question 26

what learning system occurs in the cerebellum?

Answer 26

learning through error corrections

Question 27

define reinforcement learning

Answer 27

· Learning is based on reward or punishment (good/bad) rather than on error (too much, too little, left, right) · The reinforcement signal does not directly provide information about how to improve performance (contrast with cerebellum & climbing fibre signals) · Reward based learning - try to choose strategy to maximize future rewards refer to diagram

Question 28

briefly overview instrumental conditioning / operant conditioning/ reinforcement learning

Answer 28

· Skinner box – rat, box, lever and reward · Initial exploratory behaviour · Reinforcement (learning) to repeat recent action: exploit behaviour · Balance exploration - exploitation

Question 29

how do rewards contribute to reinforcement learning?

Answer 29

· Natural reinforcers (water, food, sex) · Rewards stimulate release of dopamine (DA) · Animals will work to self-administer DA · Substances of abuse increase DA release in nucleus accumbens (NAcc, ventral striatum)

Question 30

what is the neural basis of rewards?

Answer 30

· Reward causes release of dopamine · Animal presses lever for intra-cortical electric stimulation (ICS) of dopamine neurons · Most reliable ICS sites include DA fibres: · mesolimbic: Ventral Tegmental Area (VTA) to NAcc (ventral striatum) · mesocortical: VTA to frontal cortex ·nigrostriatal: SNc to striatum

Question 31

what is the mechanism of action?

Answer 31

· ICS causes dopamine release in NAcc / striatum / cortex (rewarding effect) · Potentiates the glutamate transmission in cortex · Leads to strengthening of cortical inputs to striatum · Long term potentiation (LTP) of synapses · Reinforces behaviour over long-term. Can lead to habit forming – actions are performed even when they are no longer rewarding (addiction).

Question 32

summarise action in the brain

Answer 32

· The basal ganglia form a series of loops between cortex, striatum, pallidum, back to cortex via thalamus · Action selection – They function to select behavioural actions, depending on sensory-motor and motivation status · There are strong links to several common neurological disorders · They are involved in reinforcement learning via dopamine

Question 33

what is the dorsolateral prefrontal cortex (diPFC)?

Answer 33

· One of most recently evolved parts of the brain · Undergoes prolonged period of maturation, lasting until adulthood · Heavily connected to the Basal Ganglia and Dopamine · Active when costs and benefits of alternative choices are of interest

Question 34

what is the Wisconsin card sort test: cognitive control?

Answer 34

Must discover current ‘rule’ ppts are presented a card they have to match to one of fours options where none of them are exactly the same but 3/4 categories have something in common with it (e.g., number, shape, colour) Patients with DLPFC lesions persist with unsuccessful strategy (perseverance errors) and/or capricious errors (abandoning successful rule). Perseverance errors are when one maintains an old ruleset even when it is no longer appropriate

Question 35

give examples of selection vs specification for the central executive view of action selection

Answer 35

selection what to do? move the queen? protect the pawn? threaten the knight? specification how to do it? which grasp? what trajectory? avoid obstacles?

Question 36

what is the classical model of action?

Answer 36

* First decide what to do (select) then plan the movement (specify) * Sense, think, act * Motor system is simply the output stage sensory input -> perception -> cognition (sense, think, act) -> action -> motor output

Question 37

what is affordance competition?

Answer 37

· Instead of serial perception, cognition and action modules, we have parallel specification and selection systems · Biased competition: potential actions compete against each other within sensorimotor map, influenced by a variety of biasing factors (e.g. reward) · Decision is made through a ‘distributed consensus’ · In other words, motor control is decision-making

Question 38

define the affordance model of action selection

Answer 38

Affordance model: multiple reach options are initially specified and then gradually eliminated in a competition for overt execution, as more information accumulates If central executive, then activity should be zero until action has been selected

Question 39

how is free will related to cognition?

Answer 39

· Cognition ‘leaking’ into the motor system has ramifications for free will. · Suggests that our ‘conscious self/central executive’ does not initiate (select) behaviour. · Instead, the conscious self is alerted to a given behaviour that the rest of the brain is already planning.

Question 40

what is the libet experiment?

Answer 40

· Asked to choose a random moment to move · Motor system activity measured with EEG · Asked to watch a clock and report its position when the conscious will to move is felt

Question 41

what is the modern version of the libet experiment?

Answer 41

· Similar design as original study, but brain activity now recorded with fMRI and analysed with machine learning techniques (pattern classification) · Decision signals are decodable up to 10 seconds before they become aware

Question 42

how does the mental imagery of action look like?

Answer 42

· The motor system is similarly activated by imagining and executing a movement · Premotor cortex & SMA are activated when subjects execute or imagine a sequence of movements · Mental rehearsal improves performance · Implications for rehabilitation and brain-machine interfaces

Question 43

how do brain machine interfaces (BMIs) work?

Answer 43

· Electrical (as-well as other forms of) stimulation can modulate brain / spinal activity · Huge potential in rehabilitation · Robots can be controlled by mental imagery · Computers learn the distinct electrical brain signals associated with each movement This has rehabilitation potential

Question 44

summarise this lecture

Answer 44

* Cognition (selection) and motor (specification) systems act in parallel * Cognition 'leaks' into motor system which has ramifications for 'free-will' and 'changes-of-mind' * Mental imagery is similar to motor performance and is key to brain machines interfaces