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J Neurosci Res. 2018 Aug;96(8):1341-1352. doi: 10.1002/jnr.24248. Epub 2018 Apr 16.

Tremor severity in Parkinson's disease and cortical changes of areas controlling movement sequencing: A preliminary study.

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Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain.
Center of Biomedical Network Research on Neurodegenerative Diseases (CIBERNED), Spain.
Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain.
Neural and Cognitive Engineering group, Centre for Automation and Robotics (CAR) CSIC-UPM, Arganda del Rey, Spain.
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
Yale School of Medicine and Yale School of Public Health, Center for Neuroepidemiology and Clinical Neurological Research, New Haven, Connecticut, USA.
Faculty of Electrical Engineering and Computer Science, University of Maribor, Maribor, Slovenia.
Faculty of Biosanitary Sciences, Francisco de Vitoria University, Pozuelo de Alarcón, Madrid, Spain.
Brain Damage Service, Hospital Beata Maria Ana, Madrid, Spain.
Faculty of Health Sciences, Faculty of Health Sciences, University of Maribor, Maribor, Slovenia.
Clinical Research Unit, University Hospital 12 de Octubre, Madrid, Spain.


There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor-dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high-density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide-spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.


Parkinson's disease tremor; cortical thickness; electromyography; magnetic resonance imaging


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