When brain connections fail in Parkinson’s disease
The brain is one big network of chattering neurons, so what happens when, as in Parkinson’s disease, a part of that network breaks down? Charlotte Rae, a graduate student at the MRC Cognition and Brain Sciences Unit in Cambridge marks Parkinson’s Awareness Week by explaining her research, which looks at how brain connections fail in this debilitating disease.
When Helen wakes up each morning, she takes four different pills, and will take them again every three hours until she goes to bed. If she forgets, she finds it difficult to walk, notices her left arm shaking uncontrollably, and can’t speak properly. Helen has Parkinson’s disease, and to stave off these symptoms she will need to take her cocktail of medicines every three hours, every day, for the rest of her life.
Parkinson’s affects one in every 500 people, and is currently incurable. Unfortunately, while the physical symptoms are strikingly obvious, the causes of the disease are less clear.
We do know that in Parkinson’s patients brain cells, or neurons, that use a chemical called dopamine start to die. In healthy people a region deep within the brain, called the basal ganglia, uses dopamine to make and control movements. In people with Parkinson’s, the dopamine-using neurons in the basal ganglia are gradually lost as the disease progresses. This can happen in people as young as 40, although it is more common in those aged over 60. As the loss of these neurons continues, the symptoms get steadily worse. Patients find it increasingly difficult to perform even basic tasks like making a cup of tea or buttoning up a shirt.
Because the human brain is one big network of neurons, loss of dopamine cells in just one area can affect how the rest of the brain works. This means that in Parkinson’s disease, cells dying in the basal ganglia can have far-reaching consequences for how the whole brain functions and result in a spectrum of debilitating symptoms. As well as the movement difficulties, patients can also experience sleep problems, depression, and trouble with behavioural control.
I have been looking at how Parkinson’s disease affects these far-reaching connections between brain cells. To do this I use a technique called diffusion MRI scanning to produce maps of brain connections in living people, without the need to cut up and examine their brain tissue under a microscope. Diffusion MRI scans are collected on a doughnut-shaped brain scanner, with the patient’s head placed in the centre. The diffusion scans work by measuring the movement of water molecules in patients’ neurons, which gives us an indicator of how strong the brain connections are.
Handily for the patient volunteers, these non-invasive scans take only 10 minutes, meaning that we can gain new insights into the disease without them having to undergo lengthy or uncomfortable tests. And unlike MRI scans which measure brain activity, patients don’t need to perform a task while being scanned — they can have a nap instead.
Our results so far have shown that the brain connections in the frontal lobe, the part of the brain responsible for deciding on an action and planning it, are being degraded in Parkinson’s. When neurons in the basal ganglia die, the connections between the basal ganglia and frontal lobe are lost. This means that decisions about movements, processed in the frontal lobe, can’t get to the basal ganglia — which is crucial for making and controlling those movements.
The next step is to use the diffusion MRI technique to look at how the brain connections change over time as the disease progresses. If patients come back for repeat brain scans, then we can compare these over the years with their symptoms and build up an even clearer picture of how the brain is affected by this devastating disease.
One thing we do know is that when searching for treatments for Parkinson’s disease, researchers will need to focus not just on preventing neurons from dying, but also on the damage that occurs to the connections between them. The brain only works in harmony as a sum of its parts, so as researchers, we need to continue investigating how to get the whole brain network back in balance.