08 The Cerebellum: Circuits, Connections and Computations

Question 1

where are the deep cerebellar nuclei located and what are their names?

Answer 1

• in the hemispheres of the neocerebellum
• fastigial, interposed and dentate nucleus

Question 2

how does the intracerebellar circuit unfold?

Answer 2

two loops
- deep excitatory loop: cells of the deep nuclei are directly stimulated by the external input (from pontine nuclei (cerebral cortex), spinal cord, vestibular system)

• deep inhibitory loop: Purkinje cells are stimulated via external input through granule cells (and from inferior olive) and in turn inhibit the cells of the deep nuclei

the excitatory output (to thalamus (motor cortex)) of deep nuclei is shaped by the inhibitory action of Purkinje cells.

Question 3

where does the cerebellum receive input from?

Answer 3

1) from the cerebral cortex through the
anterior pontine nuclei
2) from several nuclei of the brainstem (including colliculi, vestibular nuclei, reticular formation, inferior olive)
3) from the spinal chord (via dorsal and ventral spinocerebellar tracts)

Question 4

Where are the outputs of the cerebellum directed to?

Answer 4

1) through the deep cerebellar nuclei to brainstem nuclei (primarily reticular formation, red nucleus, vestibular nucleus, inferior olive)
2) to the cortex through the deep cerebellar nuclei and the thalamus
3) The vestibular cerebellum partially differs from this general scheme since it projects directly to the vestibular nuclei located in the brainstem

Question 5

What does the predictive coding hypothesis state?

Answer 5

According to predictive coding hypothesis the brain creates and stores internal models of the external environments and of internal perceptions and tries to infer from those the outcome of its actions.
- usually predictive computations are implemented by feedforward models

Question 6

what are feedforward models?

Answer 6

They are understood as complementary/opposed to feedback systems. In physiology, a feed-forward homeostatic control system is a control system in which, the anticipatory effect that one intermediate exerts on another intermediate further along in the pathway allows the system to anticipate changes in a regulated variable.

Question 7

how many neurons in the brain does the cerebellum account for in comparison to the brain volume?

Answer 7

50% of the total number of neurons in the brain even though the cerebellum represents only 10% of the total volume of the brain.

Question 8

How can the cerebellum structure can be described and what does this imply?

Answer 8

Cerebellum has a uniform and homogeneous microstructure compared to the cerebral cortex. This could indicate that the functional diversity of the cerebellum derives from heterogeneous input-output connectivity that is processed through a common algorithm.
- lesion studies indicate that cognitive and affective symptoms that arise after cerebellar dysfunctions follow a similar pattern of abnormality as for motor symptoms

Question 9

What is the role of the cerebellum as a feedforward model in locomotion?

Answer 9

1) In order to make a motor-to-somatosensory prediction, cerebellum receives efference copy of motor command from the primary motor cortex.
2) This information allows the cerebellum to make a prediction with regard to the sensory consequences of such motor commands, allowing the musculoskeletal system to prepare to successfully execute a movement.
3) If there is a positive match, the pattern is maintained for the next movement.
4) The lack of a match is associated with an alert signal that is sent back to the motor cortical and subcortical areas, which activates feedback movement corrections and calibration of the forward model.

Question 10

What is the role of the cerebellum as a feedforward model in cognition?

Answer 10

One of the theories is the universal cerebellum transform related to the dysmetria thought hypothesis.
The computation that underlies the UCT is the modulation of behavior around a homeostatic baseline, without conscious awareness, and according to context.
The dysmetria of thought (English: wrong length) hypothesis says that there are damages in the cerebellum producing higher cognitive deficits similar in their pattern to cerebellum-related motor ataxia.
Cerebellar damage can give rise to cerebellar cognitive affective syndrome (CCAS) characterized by disruption of executive, visual-spatial, linguistic, and affective processing.

Question 11

what are the 3 different language impairments that the cerebellum lesions can bring about?

Answer 11

1) disruption in automatic adjustment of intact grammatical and semantic abilities to a linguistic context in sentence production.
2) disruption in automatic adjustment to a linguistic context in sentence interpretation.
3) disruption of cognitive processes essential for linguistic skills, such as analysis and sequential logical reasoning.

Question 12

What was the conclusion of the study conducted about disrupted language abilities?

Answer 12

Subjects with lesions in the cerebellum have impairments regarding the ability to adjust to a linguistic context in a sentence. They are not impaired in the production of language meaningful sentences, rather they are weakened fine-tuning abilities comparable to the one patients show in motor disorders such as apraxia.

Question 13

What are the components of the basal ganglia?

Answer 13

corpus striatum (caudate - internal capsule)
- caudate: input from multimodal cortices and motor cortices concerning eye movements
- putamen: input from somatosensory cortex, extra V1 cortices, motor cortices and auditory association areas.
- nucleus accumbens
- internal capsule: think bundle of fibers
Caudate and putamen are divided by the internal capsule.
- substantia nigra: contained in the cerebral peduncles of the mesencephalon at the base of the brain stem. Divided into reticulated and compact
- subthalamic nucleus: under the VA/VL complex of the thalamus
- globus pallidus: internal and external
- medium spiny neurons located in the striatum are the first relay station of external inputs.
- All nuclei are inhibitory apart from the STN.

Question 14

How does the direct pathway unfold?

Answer 14

excitatory input from substantia nigra pars compacta/cortex to the caudate/putamen (striatum) ⇒ inhibitory input to the GPi ⇒ inhibitory input to the VA/VL of the thalamus ⇒ excitatory input to the cerebral cortex. Inhibition of an inhibition ⇒ excitation. (faciliating movement

Question 15

How does the indirect pathway unfold?

Answer 15

excitatory input from the cortex to the caudate (striatum) ⇒ inhibition of the GPe ⇒ STN excitation from the cortex ⇒ inhibition to GPi ⇒ inhibition of thalamus. Excitation of an inhibition + excitation of an inhibition ⇒ inhibition (inhibitint movement)

Question 16

What are the cortico-basal ganglia-thalamic cortical loops?

Answer 16

motor loops
- oculomotor loop
- body movement loop

non-motor loops
- prefrontal loop
- limbic loop

trial-and-error based learning (feedback loops)
reward-based learning

Question 17

How was a reciprocal pathway connecting basal ganglia and cerebellum proved?

Answer 17

Using experiments in macaque monkeys with rabies virus: A RNA virus was used as a retrograde transneuronal tracer. Rabies virus is injected in a specific site of the brain. The virus infects the axon of the cell and travels to the soma where it can replicates. The virus follows the neural processing and is in this way transmitted retrogradely to neurones that project to the first location (first order neurones) and then to second order neurones (beginning of the connection).

Question 18

What were the conclusions of the retrograde tracing study with monkeys?

Answer 18

1. there is a disynaptic pathway from the dentate nucleus (located deep in the neocerebellum hemispheres) to the putamen;
2. there is a disynaptic pathway from the STN to dentate nucleus mediated through the pontine nuclei.
3. Also third order neurons pathways were founded: injection of virus in the GPe was significantly traced back to cerebellar nuclei in a three synaptic pathway: GPe > striatum > thalamus > deep cerebellar nuclei.

Question 19

What is evidence from PET imaging pointing to regarding the relation between BG and cerebellum in clinical and neurological disorders?

Answer 19

There is either a covarying hypermetabolism in BG and cerebellum or hypometabolism in one of the structures correlated with hypermetabolism in the other structure.

Question 20

What is sensorimotor adaptation?

Answer 20

Sensorimotor adaptation is the ability to gradually modify our motor commands in order to compensate for changes in our body and in the environment.

Question 21

What is the reward-based learning mechanism based on?

Answer 21

a positive outcome of an action leads to a strengthening of the synapse involved in the movement performed to reach a certain outcome and therefore to a repetition of the action.

Question 22

What could be the different and connected role of BG and cerebellum in the learning mechanism?

Answer 22

Cerebellum: error-based adaptation
BG: reward-based feedback

leads to acceleration and optimization in sensory-motor adaptation and movement parameters based on reward.

Question 23

What are the three stages of the reinforcement learning theory model?

Answer 23

1) Error type exploration: model-free exploration based on trial and error feedback
2) Model-based learning: the subject has already experience with a certain task, so his strategy is based on previous successful and unsuccessful experiences and therefore a map of the world.
3) Motor memory repetition: repetition of the successful behavior as a habit after many positive feedbacks as it is stored in the procedural memory => stereotyped behavior and acting.

Each of the three requires a different degree of knowledge and different real-time processing and execution during a task = different gradual ascending stages.

Question 24

What is the conclusion of the presented study about different learning stages?

Answer 24

Different learning stages are processed by different brain networks with different and connected nodes.
- in the model-free exploration, the limbic network was more active (VPC, ventromedial striatum, posterior cerebellum)
- in the model-based control, the cognitive network was more active (DPC, dorsomedial striatum, lateral posterior cerebellum)
- in the motor memory phase, a motor network was more active (pre-motor cortex, putamen, anterior cerebellum).

Question 25

Where could be the future research regarding cerebellum and BG connections directed to?

Answer 25

1) interactions of BG and cerebellum within the limbic system
2) the function of the subthalamic nucleus in BG information processing and the functional role of his link to the cerebellum
3) studies in animals without a cerebral cortex but a well-established connections between BG and cerebellum