Task 3 Flashcards
3.1: What are the functions of the basal ganglia (=BG) loops?
movement, cognition & emotion
3.1: What are the structures of the BG?
Striatum (caudaute nucleus & putamen), substantia nigra pars compacta & pars reticulata (SNc&SNr), Globus pallidus internal&external (GPi&GPe) + subthalamic nucleus (STN)
3.1. What are the main input & output structures of the BG?
- Input: Striatum
- Output: GPi
3.1: Which areas does the striatum get its input from?
Thalamus, cortex & brainstem
3.1: Direct BG pathway
-Cortex transiently excites striatum (GLU) –> Striatum transiently inhibit GPi (GABA) –> tonic inhibition of GPi on thalamus released (DISINHIBITION) –> Thalamus transiently excites cortex (GLU)
3.1: Role of SNc in direct pathway
D1 receptor –> transiently excites striatum as well (like cortex) but with DOPAMINE
3.1: Direct pathway of BG leads to what?
Movement (GO-pathway)
3.1: Indirect BG pathway
-Cortex transiently excites striatum (GLU) –> transiently inhibits GPe (GABA) –> GPe usually tonically inhibts STN (GABA) –> STN disinhibited (because GPe inhibited) –> STN transiently excites GPi (GLU) –> GPi tonically inhibits thalamus (GABA) –> so thalamus CANNOT excite cortex
3.1: SNc: D1 &D2 receptors
- D1: DOPA excites
- D2: DOPA inhibits
- -> both have effect on striatum
3.1: Indirect pathway of BG leads to what?
NO movement (NO-GO pathway)
3.1: What are the 4 different BG loops?
Motor, occulomotor, executive/associative & emotional/motivational loop
3.2: What are the two anatomical observations by Haber (2016)?
(1) Cortical inputs to striatum from functionally different regions of PFC strongly overlap in dorsal-medial striatum
(2) Spiral of connections between functionally matching topographical parts of striatum & midbrain dopamine region
3.2: What is seen in the striatum in terms of projections from other areas?
- great overlap of projections of cortex to striatum
- overlap of projections from vmPFC, OFC & dACC ==> hubs for integrating reward value, predictability & salience
- also functionally diverse projections overlap in striatum (e.g. input from dPFC)
3.2: Where in the striatum is there the most convergence of input?
anterior (rostral) striatum (see figure 1 in Haber (2016))
3.2: What do both the DA-striatal pathway & the striatal input to the DA neurons show in terms of their organization?
general inverse dorsal-ventral topographic organization
3.2: What does the spiraling of information faciliate in DA-striatal pathway?
through this spiral, information can flow from limbic to cognitive to motor circuits
3.2: How is info always channeled (from where to where?)
from limbic to cognitive to motor circuits
3.2: Is there strictly parallel processing in BG?
no, there are many interconnections
3.2: What does motivation trigger in BG (limbic loop)?
- Triggers cognitive considerations (rules that apply in the situation, do’s and dont’s)
- Triggers attentional priorities (what objects, stimuli, are relevant to realize this goal; are all the conditions met?
- Triggers action patterns (which actions can accomplish my goal?)
3.3: Where does DOPA originate from?
Substantia nigra (midbrain)
3.3: What’s the role of DOPA in the direct pathway?
- D1 receptors (stimulates)
- Stimulating stimulation
- Striatum more inhibitory – disinhibiting Thalamus
- Learning: LTP/ strengthening connection
-‚Pressing gas‘
= stronger go-signal 🡪 increases trigger readiness
3.3: What’s the role of DOPA in the indirect pathway?
- D2 receptors (inhibits)
- Inhibiting inhibition (disinhibition) = less inhibition
- Striatum less inhibitory –-> unable to completely inhibit Thalamus
- Learning: LTD / weakening inhibitory connections (if no dopamine, LTD converts to LTP)
-`Releasing brake‘
= weaker no-go signal 🡪 increases trigger readiness
3.3: Which NTs are drivers?
- Glutamate (+) & GABA (-)
- in/decreases likelihood of firing of neurons
3.3: Which NTs are modulators?
- DOPA & serotonin
- able to effect large number of neurons at the same time 🡪 affect strength of signal between the neurons
3.3: Cools et al study w/ Parkinsons: AIM
Observing set-shifting deficit in Parkinson‘s by using a switch task in a non-learning context
3.3: Cools et al study w/ Parkinsons: METHOD
- Task-switching: naming digits or letters
- 2 conditions
- -> No-cross talk: only relevant stimuli (only letter or only digit)
- -> Cross-talk: irrelevant stimuli included (letter and digit simultaneously)
3.3: Cools et al study w/ Parkinsons: RESULTS
- Evidence for deficit in cognitive set shifting in PD
- -> Independent from impairments in rule learning, WM etc
3.3: Cools et al study w/ Parkinsons: only when was there a deficit in set shifting?
Shifting deficit only in cross-talk condition –> only apparent when irrelevant information presented
3.3: Cools et al study w/ Parkinsons –> Conclusions about role of BG
- BG: selection & inhibition of competing cognitive & motor programs
- -> Evidence that BG has also role in cognition
3.3: Cools et al study w/ Parkinsons –> Conclusions about role of DOPA
DOPA facilitates focusing function by disinhibiting task-relevant corticostriatal projections & inhibiting task-irrelevant ones
3.4: Evidence BG makes decisions- What was Grillner’s (2005) observation?
-Decorticated cats: could still search for food & eat , move around & display goal-directed locomotion/behaviour
3.4: Evidence BG makes decisions- LEE ET AL (2014)
- evolutionary evidence
- evolving role of striatum in decision making
- 4: Evidence BG makes decisions- LEE ET AL (2014)
- -> ‘Ballot Box’ model
- Striatum as “ballot box”: various sensory modalities, motivation networks & cognitive systems are able to ‘vote’ for a limited set of behavioral responses
- -> Direct (= votes for) & indirect pathway (=votes against)
- 4: Evidence BG makes decisions- Cools et al (2001)
- -> Parkinson’s disease
Parkinson’s disease –> cognitive impairments even in its early stages, resembling those seen in frontal lobe patients
–> Deficits in the ability to shift set
- 5: How does BG contribute to WM?
- -> Input gating
Input gating of WM
- -> Useful info in environment => D1: gate open & WM updated
- -> Gating mediated by cortico-striatal mechanism
- -> Causes a go cell to fire & facilitates thalamic-PFC info flow for WM updating
- -> Distracting info triggers No-go cells
- 5: How does BG contribute to WM?
- -> Input gating ==> fMRI EVIDENCE
- striatal activation –> WM tasks that require updating (D1 receptors active)
- D2 –> no go cells ==> limit WM update
- 5: How does BG contribute to WM?
- -> Output gating
- Single out or select relevant representation stored within WM
- Higher order plans can select motor plans via corticostriatal circuits
3.5: How does BG contribute to WM?
–> Output gating
==> fMRI EVIDENCE
-used a task: 3 sequentially presented stimuli (2 items, 1 context)
-if context appears last –> output gating
==> BOLD response in pre-motor cortex
- 5: Reallocation of WM & BG
- -> What is tracked by BG?
- -> study
- Utility of WM for future behaviour is tracked possibly by BG
- PP required more time to reallocate
3.6: Ballot box model of striatum
o Striatum: like ballot box
o Massive convergence of input onto striatum
o All of sensory & motivation systems etc: can all vote
o Movement with most votes –> will be executed
- 6: Ballot box model of striatum
- -> comparison with go/no-go model (Chatham)
xxx
- 6: Ballot box model of striatum & go/no-go model
- -> Can both pathways be active at same time?
o Ballot model: two pathways can be activated at same time
o Go-no go signal (classical model) –> two pathways cannot be activated at same time!
3.6: Chatham’s go/no-go model: How does this model place BG at the core of all forms of cognition?
- all cognition (implicit as well as explicit) requires WM activity, which is regulated by BG
- BG regulates initiation & termination of cognitive processes = i.e. planning, attention etc. (which all affect WM)
What changes in Parkinson’s disease regarding the direct & indirect pathway of the BG?
- Go-pathway: disappears
- No-go pathway: turns into LTP ==> reverses effect
o Strengthens the indirect one
–> More difficult to initiate movements
