Electrophysiological dissection of the neurophysiological and neuromuscular correlates of freezing phenomena in Parkinson’s disease

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URI: http://hdl.handle.net/10900/81065
http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-810656
http://dx.doi.org/10.15496/publikation-22459
Dokumentart: PhDThesis
Date: 2018-03
Language: English
Faculty: 8 Zentrale, interfakultäre und fakultätsübergreifende Einrichtungen
Department: Graduiertenkollegs
Advisor: Krüger, Rejko (Prof. Dr.)
Day of Oral Examination: 2017-07-28
DDC Classifikation: 000 - Computer science, information and general works
610 - Medicine and health
Keywords: Parkinson-Krankheit
License: http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=de http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=en
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Abstract:

Freezing phenomena including freezing of gait (FOG) highly disturb the quality of life in patients with Parkinson’s disease (PD). Conventional therapy, like L-DOPA and deep brain stimulation of the subthalamic nucleus (STN-DBS) cannot satisfactorily relieve these symptoms, although it ameliorates most motor symptoms like rigidity and bradykinesia. These motor symptoms are primarily caused by degeneration of dopaminergic cells in the substantia nigra, which induces pathologically increased inhibitory output from the basal ganglia. STN-DBS may reduce the excessive basal ganglia output, however the working mechanism of STN-DBS and the influence on the neuromuscular network effects need further elucidation. In this context, we found that STN-DBS could lower pathologically increased low-frequency intermuscular synchronization during continuous finger tapping. Furthermore, STN-DBS strengthened the corticospinal connection during continuous finger tapping, displayed by the increased corticomuscular coherence in the tapping frequency. With respect to freezing phenomena, it is necessary to further elucidate the pathophysiological mechanism. We therefore introduced a dual task to trigger upper limb freezing (ULF). Offline we defined criteria to detect freezing episodes from the biomechanical recording. We observed that during ULF cortical activity was increased in the alpha band compared to continuous finger tapping. During ULF, this increased alpha cortical activity started over the contralateral sensorimotor cortex and spread to the contralateral frontal cortex and the ipsilateral parietal cortex during the freezing episode. Furthermore, we observed that a higher number of ULF episodes was associated with an increased cortico-cortical beta synchronization. These findings ‒ increased alpha activity and increased beta synchronization ‒ could probably function as biomarker to predict freezing phenomena. This will enable us to decipher pathophysiological mechanisms of freezing phenomena further. Consequently, using this knowledge may improve therapy to meet the therapeutic need.

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