Tremor is a neurological movement disorders characterized by involuntary shaking of one or more body parts, often in rhythmic and oscillatory pattern.
Tremor can be a disease entity of its own or may be part of a movement disorder such as Parkinson’s disease. In the Systems Neurology group, we focus on the underlying mechanisms of tremor from a pathophysiological point of view.
To this end, we utilize electrophysiological, neuroimaging, and brain stimulation techniques as well as clinical data from patients. Our ultimate goal is to improve the treatment of this disabling symptom.
Stress is a normal physiological reaction, needed to anticipate threats. However, chronic stress can lead to psychiatric disorders like depression and anxiety.
In people with Parkinson’s disease, the prevalence of such disorders is exceptionally high and symptoms worsen in stressful situations. Also, animal models of Parkinson’s disease suggest that chronic stress accelerates disease progression.
In our research, we use fMRI to investigate the cerebral mechanisms underlying this increased stress-sensitivity in Parkinson’s disease. Also, we explore how reducing stress (pharmacologically and non-pharmacologically) affects Parkinson’s disease symptom progression.
Neurodegenerative disorders such as Parkinson’s disease typically progress over very long periods of time.
As these disorders progress, brain network dysfunction becomes more and more pervasive, which drives the worsening of symptoms. However, given its neuroplastic properties, the disordered brain is able to adapt and alter the functioning of its networks in ways that counteract, or compensate for, pathological dysfunction.
The eventual decline of these compensatory mechanisms may be key to understanding symptom progression in neurodegenerative disorders.
Johansson, M. E., Toni, I., Kessels, R. P., Bloem, B. R., & Helmich, R. C. (2023). Clinical severity in Parkinson’s disease is determined by decline in cortical compensation. BRAIN, in press. This study shows that individual differences in the clinical severity of Parkinson’s disease (N=353) are determined by the integrity of cortical compensation, which we characterized as the ability to upregulate parieto-premotor cortex activity in response to mild cognitive load. This conflicts with the traditional view that attributes motor symptoms, and bradykinesia in particular, to loss of dopamine and basal ganglia dysfunction, which we found to be similar between individuals despite marked differences in symptom severity.
Johansson, M. E., van Lier, N. M., Kessels, R. P. C., Bloem, B. R., & Helmich, R. C. (2023). Two-year clinical progression in focal and diffuse subtypes of Parkinson’s disease. NPJ Parkinson’s disease, 9(1), 29. https://doi.org/10.1038/s41531-023-00466-4. In this study, we validate a set of clinical subtyping criteria, originally developed for de novo Parkinson’s disease, in a cohort of individuals in the early-to-moderate disease stages (N=499). Consistent with the original classification, we show that a relatively severe diffuse-malignant subtype (N=210) is characterized by involvement of additional clinical domains, less focal motor symptoms, and faster clinical progression compared to a more benign mild-motor predominant subtype (N=59), potentially reflecting differences in underlying pathological processes, such as the propagation of alpha-synuclein.
Dirkx, M. F., Shine, J. M., & Helmich, R. C. (2023). Integrative brain states facilitate the expression of Parkinson’s tremor. Movement Disorders. This study investigates the cerebral mechanisms responsible for spontaneous fluctuations of Parkinson’s tremor. We found that integrative brain states create an environment for the occurence of tremor, which is then likely amplified by the ascending arousal system.
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