Parkinsonism: Introduction and Basal Ganglia Circuitry

00:01 In this talk, we're going to review Parkinson's disease.

00:04 And we'll start with an introduction.

00:08 So first, let's talk about what Parkinsonism is.

00:12 This is really a constellation of symptoms.

00:14 Classically, we see this as a chronic, progressive neurodegenerative disorder affecting the central nervous system with four cardinal features.

00:23 And I want you to remember these four cardinal features, which are present in any patient who presents with a Parkinsonism.

00:31 The first is bradykinesia, rigidity, postural instability, with or without tremor.

00:38 And when you see these four symptoms, you're going to think Parkinsonism is the cause.

00:42 And when you think Parkinsonism, these four cardinal features will come to your mind.

00:47 Any patient presenting with bradykinesia, rigidity, postural instability, with or without tremor has an underlying Parkinsonism.

00:58 Parkinsonism comes from the basal ganglia.

01:00 So let's spend a few minutes talking about what the basal ganglia is and how it works.

01:05 The basal ganglia is involved in both motor and non motor functioning.

01:10 We think about the motor functions, but there's important non-motor control that also comes from the basal ganglia.

01:16 Of the motor functions, the basal ganglia is important in the initiation of movement, helps us to start moving.

01:23 And so pathology of the basal ganglia results in difficulty with initiating movement that contributes to the bradykinesia.

01:30 And we also see postural instability and rigidity.

01:35 Let's look a little bit closer at the basal ganglia circuitry.

01:39 How does it work? What are the players what are the key brain structures involved in the basal ganglia? Well, we're going to start up with the cerebral cortex and the cortex talks to the basal ganglia to help with initiation of movement.

01:51 If you need to move the cortex has to tell the basal ganglia that you need to move.

01:57 The first key players in the basal ganglia will be the caudate and the putamen.

02:02 And inputs into the basal ganglia will come through the striatum, which is the caudate and putamen.

02:09 Moving deeper, we find the globus pallidus.

02:11 And you can see where that sits on the schematic here.

02:14 The globus pallidus is going to be an important relay and output structure from the basal ganglia.

02:20 Information is going to relay in the basal ganglia, including pathways to the substantial nigra as well as other areas and ultimately arrive at the globus pallidus, which sends information back to the thalamus.

02:34 The thalamus will be the key relay center talking back to the cortex and helping the body to start to move.

02:43 So when you think about basal ganglia circuitry, there's three things I want you to remember.

02:47 First is to initiate movement, the cortex has to tell the basal ganglia, I want to move.

02:53 The second is the thalamus.

02:55 The thalamus acts as a brake on movement, it stops movement.

02:58 And so the goal of the basal ganglia is to take the foot off the brake.

03:02 And we're going to talk about two pathways that take the foot off the brake and help to modulate and initiate that movement.

03:14 When you think about the basal ganglia, there's a few ways to break it down.

03:17 The first is the inputs and the outputs.

03:20 All information into the basal ganglia come in through the striatum.

03:24 It's the major input center, relay center for the basal ganglia.

03:28 So the cortex is going to talk to the basal ganglia through the striatum, it's the major input pathway.

03:35 And then their outputs, all of the output from the basal ganglia is going to come from the globus pallidus.

03:41 There are relay circuits within the basal ganglia that will modulate the signal, but ultimately it will arrive at the globus pallidus, which will talk to the thalamus.

03:50 All outputs come from the globus pallidus.

03:54 I also want you to know the direct and indirect pathway and these two pathways are involved in helping to take the foot off the brake so you can move or put the foot back on the brake if you need to modulate that movement.

04:07 Let's first focus on the direct pathway and see how that works.

04:11 The first step in the direct pathway is the motor cortex has to talk to the striatum and tell the body that it wants to move.

04:18 We also see inputs into the striatum from the substantia nigra pars compacta.

04:23 And that's going to be important in Parkinson's disease.

04:25 Both of those are activating the striatum, they're excitatory signals.

04:30 The striatum talks to the globus pallidus internus and to some degree, the substantia nigra pars reticulata and inhibit signals since an inhibitory signal to the globus pallidus interna.

04:44 The output from the globus pallidus interna is to the thalamus and that's an inhibitory signal, putting your foot on the brake, and the thalamus then talks back to the motor cortex.

04:58 So the goal of the direct pathway is to take the foot off the brake.

05:02 The motor cortex stimulates the striatum, the striatum inhibits the GPI.

05:07 And the GPI is not able to inhibit the thalamus, the result is the foot comes off the brake and the body can move.

05:14 And that's the goal of the direct pathway.

05:17 In Parkinson's disease, we lose that activation of the striatum, and loss of the activation of the striatum causes the foot to rest on the brake, and patients are bradykinetic rigid with postural instability.

05:33 Now let's turn to the indirect pathway.

05:36 Indirect pathway involves some of the similar players - motor cortex, striatum and GPI, but we have some other areas of basal ganglia circuitry that are involved.

05:46 Again, this pathway starts in the motor cortex and the motor cortex activates the striatum.

05:52 All inputs to the basal ganglia are through the striatum.

05:55 But here there's some alternative circuitry involved.

05:58 The substancia nigra inhibits the striatum in the indirect pathway.

06:03 The striatum inhibits the GPe the globus pallidus external, which inhibits the subthalamic nucleus, a and that sends excitatory fibers and circuitry to the GPI, the globus pallidus internus, which then inhibits the thalamus.

06:20 So this is a more complex circuitry.

06:22 And the key thing to remember here is the goal of the indirect pathway is to prevent unwanted muscle movement from getting in the way of voluntary motor movements and tasks.

06:33 Here in Parkinson's disease, we have loss of that inhibitory signal to the striatum.

06:39 So the striatum is free to do what it does.

06:42 And this results in an increase in resistance from the GPe And it's important in Parkinson's disease to remember both the direct and indirect pathways, one taking the foot off the brake, the other putting the foot on the brake.

06:57 And in Parkinson's disease, we have abnormal circuitry, resulting in less movement in these patients.