Post by Elisa Guma
What's the science?
Deep brain stimulation (DBS) is an effective and established treatment for Parkinson’s disease, wherein electrodes are implanted in a targeted brain area in order to relieve certain symptoms such as tremor, stiffness and rigidity, and impaired gait. The mechanism by which DBS is thought to improve symptoms is still not fully understood. It was previously thought that improvements were solely due to localized stimulation of specific brain regions, however, they may be due to more global changes in functional brain networks. This week in Brain, Horn and colleagues investigated the effects of DBS on functional brain networks of patients suffering from Parkinson’s disease.
How did they do it?
The authors acquired resting-state functional magnetic resonance imaging (rs-fMRI) data in 20 Parkinson’s patients who underwent surgery to place DBS electrodes in the subthalamic nucleus (STN), and 14 healthy, age-matched controls. RS-fMRI is a technique that measures fluctuations in blood oxygenated level-dependent (BOLD) signals in the brain, which allows for a measure of intrinsic associations between the brain activity of specific regions based on the correlation of signal over time between those brain regions. Patients were first measured with their electrodes turned on, and after a short break, were scanned again with their electrodes turned off in order to see how the electrical stimulation affected global brain activity.
The data was processed using state of the art software, Lead-DBS, which allowed for the localization of the DBS electrodes, as well as analysis of brain volume and activation, with careful regard for artefacts due to motion during scans and metal from the electrodes. This allowed the authors to analyze how the electric field of the DBS-electrodes modulated brain activity in a key motor network referred to as the basal ganglia-cerebellar-cortical loops. These loops include the sensorimotor functional zones of the cortex, striatum, thalamus, internal and external globus pallidus, substantia nigra, and cerebellum. They compared functional brain networks in the DBS-on and -off conditions to those of healthy controls. Further, they investigated how electrode placement modulated the patterns in brain activity they observed.
What did they find?
First, the authors found that the accuracy of the electrode placement within the STN determined the strength of connectivity between the STN and the supplementary motor area (a motor network region); the better the placement, the stronger the connectivity between these two regions. Next, they found that connectivity maps between the volume of tissue activated around the STN and the motor network were most similar between DBS-on conditions and healthy controls, suggesting that DBS electrode activity might normalize brain networks towards healthy controls. This was also affected by the electrode placement. Finally, the authors found that connectivity in the DBS-on group was increased in the motor network (between the thalamus and cortex), with a decrease in basal ganglia connectivity (striatum to cerebellum, STN, and STN to globus pallidus).
What's the impact?
This study is one of the first to demonstrate the feasibility of conducting rs-fMRI in DBS implanted patients. They identify that DBS has a significant effect on brain connectivity throughout the motor network and that these changes were strongly dependent on correct electrode placement. The findings are promising evidence for the use of invasive neuromodulation. Further, DBS provides a framework within which to study how brain networks change in response to targeted stimulation, which could be applied to other populations undergoing DBS treatment, such as those with depression, obsessive-compulsive disorder, or eating disorders.
Andreas Horn et al. Deep brain stimulation induced normalization of the human functional connectome in Parkinson’s disease. Brain (2019). Access the original scientific publication here.