Parkinson's disease as I showed you, it's the other side of the story. So you have the indirect pathway and that's where mainly Huntington's disease defect is. And the Parkinson's is more in the direct pathway. Now pathology wise if you take a cut at that level and you look at the spring structure called substantia nigra, [FOREIGN]. You will see in normal people, you have these black cells and in patient of PD, those black cells disappear. Those are dopaminergic cells. Modern technology of brain imaging helps us to monitor the progression of that disease. Here, we labelled dopamine and inject, and since the receptors are all in that area, right? So dopamine goes to those places, and you can see how the strength of the signals are. This patient we follow that for basically four years, and more red means there's more dopamine. Okay, you can see this patient overall the both sides are weakening. However, left side the progression is much stronger, right? And that's one thing typical in Parkinson's disease. Almost all patients, they have asymmetric development. Okay, I'm going to show you a video of that later. So this is a patient, I want you to watch a movie. And it has typical Parkinson's diease symptoms, including mask face [FOREIGN] called the mask face. When he is speaking, the voice is slow and also monotonous. [FOREIGN] not very expressive, not with lots of tones up and down. And he has resting tremor, we have lots of diseases that people have tremor. But Parkinson's disease, the tremor is called a resting tremor. A rest tremor means I'm not doing anything and I'm shaking. Other types are if I'm trying to grab something then I start to shake, it's a different one. Now, everybody do things like me. Your right hand please and do this. Okay, make sure you have a big movement, okay and follow me and make it faster and keep doing that. Yours is not big enough. Okay, very good. I'm glad to tell you, you don't have Parkinson's disease. >> [LAUGH] >> And, in the patient, such kind of movement, first of all, the rhythm is broken. So, he cannot do like this, he will do like, So, the rhythm is off. Second, the amplitude [FOREIGN] he can not maintain, such big things, for 30 seconds or a minute. So he will do this and then, like that. So these are, believe it or not, our first line of testing the patients. Okay, now I told you that the two sides are not the same, so one side is better. So when we ask him to do this, one side is fine. The other one is like, it can not move, so it will be like this. And if you ask him to tap the legs, one side he can do it. The other one, the rhythm and amplitude is small. Okay so let's watch the movie. Not this one. >> Have you guys changed your voice at all? >> [INAUDIBLE] >> And you said, >> Resting tremor? >> [INAUDIBLE] so I imagine it's just related to [INAUDIBLE] >> Yeah, that's what I think. >> [INAUDIBLE] >> So the right side is worse. >> [INAUDIBLE] of your symptoms. >> [INAUDIBLE] >> Okay, keep going, again, good, arms out in front of you. >> See the right hand is shaking. >> [INAUDIBLE] >> Left hand is relatively okay. >> Fast as you can, really big movement. Good, same on the left. >> This is much better, right? >> Both hands go like this. And then side to side good, okay, with the right foot, just stomp it on the floor. Faster, and now with. Okay, can you fold your arms in front of your chest and stand up? Turn to the file cabinet, turn and come back. >> See one arm is, like, swinging and the other one is not, see that? Okay, all right. Here I show again the substantia nigra and a bigger picture of the cellular aggregation, the Lewy body. Okay, it's a huge structure inside the cell with a halo around it. The Lewy body, the main component is alpha synuclein.