Cycle 4 project 5

Towards a non-invasive approach to evaluate abnormal network oscillations in Parkinsons’s Disease: combined tACS and fMRI studies


kathleen-williamsPhD student: Kathleen Williams, United States
Home Institute: European Neuroscience Institute Göttingen; Principle Investigator: Melanie Wilke / Mathias Bähr
Host Institute: Neuroscience Center Zürich; Principle Investigator: Achermann, Peter
2nd Host Institute: Amsterdam Neuroscience; Principle Investigator: Henk Berendse

Executive Summary

Recent advances of functional imaging and network analysis techniques have led to the broad consensus that cognitive deficits that occur in the course of neurodegenerative disorders are not only due to circumscribed lesions in specialized brain structures, but are also due to disruptions of functional networks1. Parkinson’s disease (PD) is one of these common age-related disabling disorders characterized by the well known motor symptoms (rigor, tremor, hypokinesia) but also by non-motor symptoms such as sleep, affective and cognitive dysfunctions2. Abnormalities in cortico-basal ganglia-thalamocortical circuits have been implicated in many of these PD symptoms and proposed as a marker for presymptomatic progression of the disease3. Thus, the development of sensitive and reliable methods to assess the state of functional brain networks in PD will be an important step towards the development of improved diagnostic methods that may pave the way for timely therapeutic interventions. While most of the network analysis in PD to date has been

performed by measuring slow (< 0.1Hz) co-variance patterns with PET and fMRI techniques, it became increasingly clear from non-invasive MEG and invasive, surgical recordings from subcortical structures in PD patients, that clinically relevant abnormal synchronizations occur in higher frequencies such as the beta band (> 10 Hz)4-6. However, MEG techniques cannot measure activity in subcortical structures. In order to circumvent this problem, we have recently developed another non-invasive approach that combines transcranial alternating current stimulation (tACS), which is thought to entrain endogenous neuronal oscillations7, with fMRI. We recently found evidence for the feasibility of this approach in a study in healthy subjects, where we compared tACS-evoked BOLD activity as a function of stimulation frequency and behavioral task. Our study revealed robust BOLD activation in fronto-parietal areas as well as in the basal ganglia with tACS stimulation, which was selective for the beta frequency (16 Hz) range8. Since the beta-stimulation evoked BOLD activity was strongly reduced during execution of a motor task (known to suppress beta oscillations), it likely reflects the functional state of the network.

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