Basal Ganglia (Rosenstein)

see image of the striatum

*THE CAUDATE AND PUTAMEN ARE CONTINUOUS STRUCTURES that are broken up by the internal capsule* --> But you can see the stripes/fibers connecting the two structures

Location of the caudate nucleus The tail of the caudate nucleus is continuous with what structure?

-Tail is continuous with the amygdala! -The caudate nucleus parallels the lateral ventricle and corpus callosum

List all the functions of the basal ganglia - read slide too

A. (Voluntary) movement control: 1. Involved in the planning phase of a movement 2. Contributes to the speed of particular movements 3. Contributes to movements learned by repetition B. May link motivation and emotion to the execution of movements. C. Involved in procedural learning and habits/routine behaviors

BASAL GANGLIA CONNECTIONS

BASAL GANGLIA CONNECTIONS

What is basal ganglia function based upon?

Basal ganglia function is based on *significant loops of fiber connections from the cortex through these nuclear structures to the thalamus and back to the cortex*. These loops run in parallel with one another and process different kinds of information and participate in different tasks. The end result is that connections and impulses are directed back upstream --> higher cortical (mostly motor and some cognitive) impulses are modified in the basal ganglia, sent back to their place of origin and then sent through descending cortical tracts.

Path of a fiber loop through the basal ganglia

CORTEX→ BASAL GANGLIA→ THALAMUS→ CORTEX→ PYRAMIDAL and EXRAPYRAMIDAL TRACTS

What is Cerebral Palsy/Birth Asphyxia?

Cerebral palsy is associated with basal ganglia but not associated with dopamine!! It is about the blood vessels in the basal ganglia (the penetrating vessels). Has a spectrum of injury states typically in children. Birth asphyxia = another name for cerebral palsy. Baby loses a lot of oxygen and this will affect MCA/penetrating arteries —> so infant basically has a stroke problem (but they can be treated rapidly - so sx can range from mild to severe) >Maternal infection/injury or genetic issues can cause cerebral palsy

What is Tourette's Syndrome?

Condition characterized by involuntary movements or tics occurring at regular intervals and/or explosive inappropriate vocalizations. Children affected often show hyperactivity and unusual creativity. *Appears to be a dopamine-related condition in the basal ganglia*

What is characteristic of all diseases of the basal ganglia?

Diseases produce a mixture of motor symptoms due to loss or increase of neural activity at some point in the loops. There can be abnormally pronounced involuntary movement (dyskinesia) as well as reduced initiation of movement (akinesia) - followed by slower and smaller movements (bradykinesia or hypokinesia)

What is characteristic of Huntington's disease?

Dominant/inherited disease with genetic defect found on chromosome 4. *Causes loss of GABA neurons in the striatum and frontal lobe of cortex*. Produces rapid, jerky involuntary movements of face, arms and legs coupled with rapid mental deterioration. Athetosis is closely related, having similar but slower movements HYPERKINETIC BECAUSE NOT ENOUGH INHIBITION FROM THE BG ONTO THE THALAMUS (no GABA!)

When the substantia nigra projects to the other basal ganglia structures, what neurotransmitter does it use?

Dopamine The nigrostriatal pathway is the most important dopaminergic pathway.

What is Parkinson's disease caused by? What are the characteristic symptoms/signs?

Due to: pronounced loss of dopamine in the striatum due to *death of substantia nigra neurons.* --> Parkinsons is idiopathic, we do not know what causes the deaht of the neurons. However, up to 80% of neurons in the substantia nigra must be lost for a patient to exhibit symptoms. Characterized by akinesia, bradykinesia, lack of facial movements, *increased muscle resting tone (rigidity) and involuntary rhythmic movements - resting tremor.* HYPOKINETIC BECAUSE TOO MUCH INHIBITION FROM THE BG IS PLACED ON THE MOTOR CENTERS OF THE THALAMUS (VA and VL nuclei)

Is the final efferent output from the thalamus to the cortex inhibitory or excitatory?

Excitatory!

True or false: Basal ganglia also has direct connections with the cerebellum and the spinal cord.

FALSE - the BG does not have connections with either of these structures

The cortex to the striatum uses what neurotransmitter?

Glutamate

Describe the symptoms of Parkinson's in more detail -pill rolling -posture -muscle rigidity

Have positive (movements they don't wanna do - resting tremor and posture) and negative signs (muscle rigidity) Pill rolling movement = ADVANCED cases and really the only movement that occurs with Parkinson's. Earlier onset Parkinson's will get neck rolling movements instead of pill rolling. Posture = because they have rigidity, they bend over a little. Can't swing arms and will shuffle forward. Muscle rigidity = increase in tone and lead-pipe/cogwheel rigidity

More details about Huntington's How do the neurons die in Huntington's?

Huntington's = main hyperkinetic disorder NO CURE AND NO THERAPY (so mainly palliative care) It is a very rare genetic disorder where all the GABAergic neurons die (first in cortex and then in the caudate nucleus) —> leads to lack of judgement and personality. Huntington's patients do not live very long. The death of the neurons occurs as a wave (cortex —> caudate —> globus —> rest of brain and brainstem) The caudate is messed up -> globus is messed up —> thalamus is more active!!! Leads to more activation of cortex leading to increased rapid movements

What are some examples of hyperkinetic diseases?

Huntington's disease Hemiballismus Tourette's Syndrome

Caudate nucleus and amygdala in cross section

Imagine the body of the caudate nucleus going back into the screen (away from you) and the tail wrapping back around to attach to amygdala

Is the final efferent output from the basal ganglia to the thalamus inhibitory or excitatory?

Inhibitory!

What is the effect of a lesion to the basal ganglia on a person's movement?

Lesions of the subcortical basal ganglia result in abnormalities of movements that are disorganized and uncoordinated. *The basal ganglia do not project directly to the spinal cord or brainstem* but rather affect movements by influencing the motor output of the cortex. ...Whereas lesions of the cerebral cortex itself would result in total loss of movement (paralysis)

See location of the globus pallidus

Note that it cannot easily be seen with a sagittal cut straight down the middle

What is the major example of a hypokinetic basal ganglia disorder we discussed?

Parkinson's disease

What do most patients with Parkinson's die of?

Parkinson's disease itself is NOT FATAL - can live a long time with medications and being careful Most patients will die from either a fall (due to rigidity) or from choking (because of loss of swallowing mechanism)

Striatum to the Globus Pallidus projection

Projections are modified even further

What is the function of the septal area?

Septal area is circled • Pleasure area - where dopamine is really important • Dopamine released from substantial nigra and goes into the septal area

Substantia nigra to the Striatum projection Type of info carried? NT?

Substantia Nigra to the Striatum = GABA neurons = inhibitory!! ◦The dopamine is MODULATORY and controls what is happening in the striatum

Location of substantia nigra

Substantia nigra = The black substance shown • Predominantly dopamine containing neurons but also contain melanin!!!

Location of subthalamic nucleus

Subthalamic nucleus fibers will project right up in the globus pallidus

What are the basal ganglia? Main function?

The basal ganglia are fairly large masses of mostly gray matter buried under the cerebral cortex that are involved in the control of movements. Diseases of the basal ganglia such as Parkinson's disease thus produce characteristic, unusual disturbances of movement.

Where does the caudate nucleus receive input from (i.e. its afferent inputs)?

The caudate nucleus receives fibers from association cortex- regions that are concerned with motor control and some mental function.

Which parts of the basal ganglia send out efferent fibers?

The effects exerted by the basal ganglia on other parts of the nervous system are mediated primarily by *efferent fibers from the globus pallidus and substantia nigra*

Knowing that the final efferent output of the BG to the thalamus is inhibitory, but the final efferent output of the thalamus to the cortex is then excitatory, what is the specific role of the BG in these pathways?

The key function of the basal ganglia is the *inhibition/modulation of impulses* that begin in the cortex and end up back in the cortex.

Where does the putamen receive input from (i.e. its afferent inputs)?

The putamen receives organized inputs from the primary motor and sensory cortical areas

Where does the striatum receive input from (i.e. its afferent inputs)? 3 places

The striatum is largely the receiving portion of the basal ganglia. Receives excitatory input from the cortex, thalamus and substantia nigra

Where is the subthalamic nucleus located?

The subthalamic nucleus is part of a small but significant internal loop *between the globus pallidus and the substantia nigra.*

What are the specific structures that make up the basal ganglia?

The term basal ganglia includes the caudate nucleus, the putamen and the globus pallidus. -caudate nucleus -putamen -globus pallidus -substantia nigra -subthalamic nucleus note: the substantia nigra and subthalamic nucleus are also included because of their proximity and fiber connections

What are some conditions that can mimic Parkinsons?

There are many disorders that mimic Parkinson's - anything that messes up the basal ganglia connections (that we learned earlier): >One of those is *Atherosclerotic Parkinsonism* - lacunar stroke that occurs in the penetrating arteries —> leads to issues with dopamine release leading to rigidity, etc >Patient could fall and injure these areas of the brain too >Lewy body diseases, etc —> start off with intense tremors but are NOT Parkinson's

What is the function of the nigrostriatal pathway? What diseases are associated with alterations in this pathway?

This pathway modulates responses of striatal neurons to inputs from cortex or thalamus. Dopaminergic transmission is involved in Parkinson's disease, Schizophrenia and Tourette's syndrome and *can be either excitatory or inhibitory.*

What is dyskinesia?

abnormally pronounced involuntary movement

All the efferents FROM THE CORTEX must travel through the __________________.

internal capsule

What is akinesia?

reduced initiation of movement

What is bradykinesia or hypokinesia?

slower and smaller movements

Information from the ___________ is processed in the globus pallidus and substantia nigra.

striatum

Putamen and globus pallidus together are called what?

the lenticular nucleus; looks like a LENS for lenticular nucleus • Putamen = afferent whereas globus = efferent!!

See the location of the putamen

the putamen is shown in green

Caudate and putamen together are called what?

the striatum (pink stripes in the image are the striatum)

True or false: Basal ganglia has a connection to the prefrontal cortex (and the amygdala... thus it has an emotional context too

true

True or false: small strokes along the course of the MCA, particularly lenticulostriate arteries, can produce similar symptoms to diseases of the basal ganglia.

true

What is hemiballismus? What part of the basal ganglia is involved?

wild, flailing movements of arms and legs due to *lesion in the subthalamic nucleus.* Hemiballismus is due to the lesion or stroke in the subthalamic nucleus (which normally connects with globus) —> so lesion in this leads to inhibition of globus —> excessive flailing movements

Cortex to the Caudate projection Type of info carried? NT?

◦Caudate receives input from prefrontal and frontal cortex (behavior and personality) ◦EXCITATORY - due to this being a glutamatergic projection (the cortex wants to DO something)

Globus Pallidus to the Thalamus projection

◦Under normal conditions (when we aren't doing anything), it is all inhibitory ◦When we want to DO SOMETHING, the cortex will make this projection slightly less inhibitory —> leads to activity ◦The thalamus is always wanting to tell the cortex to do something so that is why under normal conditions it is inhibited to prevent us from having unnecessary movement all the time ◦THIS PROJECTION IS WHAT GETS MESSED UP IN MANY BG CONDITIONS