Researchers Discover Region of the Brain Thought to Play Role in Parkinson’s Symptoms

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Parkinsonism – slowed movement, muscle rigidity and tremor – is a classic set of neurological symptoms most often seen in patients with Parkinson’s disease. Because neuron loss in the substantia nigra – a region of the brain associated with motor planning – is the hallmark characteristic of Parkinson’s disease, parkinsonism has long been thought to originate there. However, parkinsonism can occur in patients who have other conditions that leave the substantia nigra intact, making the true source of the suite of symptoms a mystery. 

Now, a team of investigators led by neuroscientists at Beth Israel Deaconess Medical Center has identified the claustrum – a little understood sheet of neurons thought to play a role in sensory integration – as the likely origin of parkinsonism across different conditions. Featured as an Editor’s Choice, the study was made available free to the public today in the journal BRAIN. 

The team used a novel methodology called lesion network mapping to discover the origins of parkinsonism in 29 patients whose symptoms were not the result of Parkinson’s disease but rather attributed to a brain lesion – an abnormality or injury to the brain visible on brain imaging. The lesion network mapping technique was pioneered by senior author Michael Fox, MD, PhD, Co-Director of the Deep Brain Stimulation Program at BIDMC and an Associate Professor in Neurology at Harvard Medical School. 

The mapping of the 29 lesions – which were located in different regions of the brain – revealed that connectivity to the claustrum was the single most sensitive and specific marker of lesion-induced parkinsonism. The teams’ findings also suggest the claustrum could serve as a potential novel treatment target in brain disorders causing parkinsonism.

“The role of the claustrum has been a mystery for neuroscientists for decades and its role in the neuropathology of parkinsonism has received little attention,” said Juho Joutsa, MD, PhD, a research fellow at Massachusetts General Hospital Martinos Center and BIDMC’s Berenson-Allen Center. “These findings encourage us to further investigate the claustrum. Next we aim to better characterize the abnormal function of the claustrum in parkinsonism syndromes.”

Lesion network mapping leverages brain connectivity information (housed in a database called the Human Connectome) to discover the brain regions connected to brain lesions – areas of the brain that appear abnormal in brain imaging tests. Fox and colleagues have previously used the method to reveal which parts of the brain are responsible for a number of symptoms, conditions, behavior, and even consciousness. 

Joey Hsu of the Berenson-Allen Center and Andreas Horn, MD, of Charité – Universitätsmedizin Berlin, Germany also contributed to this paper.

Dr. Joutsa was supported by the Academy of Finland (grant # 295580), the Finnish Medical Foundation, the Orion Research Foundation and the Finnish Brain Foundation. Dr. Horn was supported by DFG KFO247, Thiemann Foundation, Berlin Institute of Health, Stiftung Charité. Dr. Fox was supported by the Dystonia Medical Research Foundation, National Parkinson Foundation, Nancy Lurie Marks Foundation, Mather’s Foundation, and the NIH (K23NS083741, R01MH113929). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR023043 and S10RR023401.