What happens in your brain when you get Parkinson's disease?

Updated

In Parkinson's, dopamine neurons in the substantia nigra die, reducing dopamine to the putamen. This overactivates the subthalamic nucleus and internal globus pallidus, which overly inhibits the thalamus, weakening motor cortex drive to muscles, causing slowness and rigidity.

Substantia Nigra, Putamen, Subthalamic Nucleus, Globus Pallidus, internal segment, Ventral Anterior Nucleus, Motor Cortex lit up on the Brain Atlas 3D brain: what happens in your brain when you get Parkinson's disease
Figure. The brain regions that light up when you get Parkinson's disease, in order: Substantia Nigra (dopamine loss), then Putamen (striatal imbalance), then Subthalamic Nucleus (overactive stn), then Globus Pallidus, internal segment (overinhibition), then Ventral Anterior Nucleus (thalamic brake), then Motor Cortex (movement block).

Watch it light up on the 3D brain

Brain regions that light up

OrderRegionWhat it does here
1Substantia NigraDopamine-producing neurons in the substantia nigra degenerate.
2PutamenReduced dopamine disrupts the putamen's control of basal ganglia pathways.
3Subthalamic NucleusThe subthalamic nucleus becomes hyperactive due to loss of inhibition.
4Globus Pallidus, internal segmentThe internal globus pallidus fires excessively, inhibiting the thalamus.
5Ventral Anterior NucleusThe thalamus is overly inhibited, reducing its excitatory drive to the motor cortex.
6Motor CortexReduced thalamic input leaves the motor cortex underactive, causing bradykinesia and rigidity.

1. Substantia Nigra: dopamine loss

Step 1 of what happens in your brain when you get Parkinson's disease: Substantia Nigra lit on the Brain Atlas 3D brain
Figure 1. Substantia Nigra, dopamine loss: Dopamine-producing neurons in the substantia nigra degenerate.

The substantia nigra pars compacta normally sends dopamine to the striatum. In Parkinson's, these neurons die, causing profound dopamine deficiency. This loss is the pathological hallmark of the disease.

2. Putamen: striatal imbalance

Step 2 of what happens in your brain when you get Parkinson's disease: Substantia Nigra, Putamen lit on the Brain Atlas 3D brain
Figure 2. Putamen, striatal imbalance: Reduced dopamine disrupts the putamen's control of basal ganglia pathways.

The putamen is the main input nucleus of the basal ganglia receiving nigral dopamine. Without dopamine, the direct pathway is underactive and the indirect pathway overactive, leading to abnormal circuit output.

3. Subthalamic Nucleus: overactive stn

Step 3 of what happens in your brain when you get Parkinson's disease: Substantia Nigra, Putamen, Subthalamic Nucleus lit on the Brain Atlas 3D brain
Figure 3. Subthalamic Nucleus, overactive stn: The subthalamic nucleus becomes hyperactive due to loss of inhibition.

Normally, the external globus pallidus inhibits the subthalamic nucleus, but in Parkinson's that inhibition is reduced. This leads to excessive excitatory output from the STN, driving the internal globus pallidus.

4. Globus Pallidus, internal segment: overinhibition

Step 4 of what happens in your brain when you get Parkinson's disease: Substantia Nigra, Putamen, Subthalamic Nucleus, Globus Pallidus, internal segment lit on the Brain Atlas 3D brain
Figure 4. Globus Pallidus, internal segment, overinhibition: The internal globus pallidus fires excessively, inhibiting the thalamus.

The GPi is the main basal ganglia output nucleus. In Parkinson's, its neurons become overactive and fire in abnormal patterns, sending strong inhibitory signals to the thalamus.

5. Ventral Anterior Nucleus: thalamic brake

Step 5 of what happens in your brain when you get Parkinson's disease: Substantia Nigra, Putamen, Subthalamic Nucleus, Globus Pallidus, internal segment, Ventral Anterior Nucleus lit on the Brain Atlas 3D brain
Figure 5. Ventral Anterior Nucleus, thalamic brake: The thalamus is overly inhibited, reducing its excitatory drive to the motor cortex.

The ventral anterior thalamic nucleus relays basal ganglia output to the frontal cortex. When GPi inhibition is too strong, the thalamus cannot properly excite the motor cortex, impairing movement initiation.

6. Motor Cortex: movement block

Step 6 of what happens in your brain when you get Parkinson's disease: Substantia Nigra, Putamen, Subthalamic Nucleus, Globus Pallidus, internal segment, Ventral Anterior Nucleus, Motor Cortex lit on the Brain Atlas 3D brain
Figure 6. Motor Cortex, movement block: Reduced thalamic input leaves the motor cortex underactive, causing bradykinesia and rigidity.

The motor cortex relies on thalamic drive to plan and execute voluntary movements. With less excitation, commands to muscles are delayed and weak, producing the slow, stiff movements typical of Parkinson's.

Good to know

  • The substantia nigra pars compacta normally supplies dopamine to the putamen via the nigrostriatal pathway.
  • Levodopa, a dopamine precursor, is a common treatment because it can cross the blood-brain barrier.
  • Deep brain stimulation of the subthalamic nucleus can improve motor symptoms in advanced Parkinson's.

Parkinson's vs. Huntington's disease

In Parkinson's, dopamine loss overactivates the indirect pathway, causing too much inhibition of the thalamus and reduced movement. In Huntington's, degeneration of striatal neurons in the indirect pathway reduces inhibition of the GPe, ultimately reducing excitation of the GPi, leading to excessive thalamic excitation and chorea. Thus, opposite motor symptoms arise from opposite basal ganglia dysfunctions.

Test yourself

  1. Which brain region shows the primary neuronal loss in Parkinson's?

  2. How does Parkinson's affect the internal globus pallidus?

  3. Which treatment targets the subthalamic nucleus to reduce symptoms?

0 of 3 answered · 0 correct

Simplified: many regions work together at once, and this shows the main players in the order they act. For learning only, not medical advice.