Credit: Naeblys / Alamy Stock Photo.
Some patients diagnosed with Parkinson’s disease develop impulsive-compulsive behaviours (ICB) such as gambling, uncontrolled spending, or binge eating. This is often described as a side effect of dopamine replacement therapy, the standard pharmacological treatment for the disease, but the reason is unclear. Now scientists have identified neurons that behave differently in patients with and without these behaviours – a finding that could help refine therapies.
The study was reported in Movement Disorders by a group of medical doctors and researchers from the Scuola Superiore Sant’Anna di Pisa, Careggi Hospital in Florence and from Università degli Studi di Firenze, in Florence1.
Parkinson’s disease is a neurodegenerative disorder that causes involuntary movements and muscle rigidity. Anxiety and depression are also common. These symptoms all arise from low levels of the neurotransmitter dopamine in the basal ganglia, an inner area of the brain below the cortex that is important for motor function. Drugs that mimic dopamine can counterbalance its shortage and reduce symptoms. But in 25% of cases, this therapy also leads to impulsive behaviour.
The researchers studied 24 patients with Parkinson’s. They had all previously been given dopamine, and half of them exhibited ICB. All of them underwent surgery for Deep Brain Stimulation (DBS), a therapy that involves placing electrodes in the brain to deliver targeted electrical stimuli, used on patients who do not respond to drugs. The electrodes were placed in the subthalamic nucleus, a section of the basal ganglia. Before switching on the stimulation, the doctors recorded the electrical activity of the subthalamic neurons in all patients. The scientists then analysed the recordings, and found clear differences between patients with and without ICB. In particular, the firing frequency of neurons in the patients with impulsive disorders was lower. Using machine learning, they created an algorithm that can recognize impulsive-compulsive patients by their neuronal activity pattern alone, with an accuracy of over 80%.
Alberto Mazzoni, an assistant professor at Scuola Superiore Sant’Anna in Pisa and lead author, says the study started out as basic research on decision-making mechanisms, and ended up pioneering machine-learning techniques on single neuron activity. “We hope these methods could pave the way for enhanced diagnosis and treatment planning” he says. In particular, they could help select the best location for DBS electrodes before surgery, so that the treatment can alleviate ICB or at least not make it worse.
In the same issue of the journal, a preliminary study2 by scientists from Consiglio Nazionale delle Ricerche and two Universities in Rome hints at another promising development for Parkinson patients: prokineticin-2, a molecule that is produced in the brain during neurodegeneration, could become a biomarker for early diagnosis or a new target for drugs.
