TY  - JOUR
AU  - Weiss, Daniel
AU  - Klotz, Rosa
AU  - Govindan, Rathinaswamy B
AU  - Scholten, Marlieke
AU  - Naros, Georgios
AU  - Ramos-Murguialday, Ander
AU  - Bunjes, Friedemann
AU  - Meisner, Christoph
AU  - Plewnia, Christian
AU  - Krüger, Rejko
AU  - Gharabaghi, Alireza
TI  - Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson's disease.
JO  - Brain
VL  - 138
IS  - 3
SN  - 1460-2156
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-04163
SP  - 679-693
PY  - 2015
AB  - Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson's disease. Here, we set out to address the motor network activity and synchronization in Parkinson's disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson's disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with 'stimulation on' compared to 'stimulation off' on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With 'stimulation on', interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to 'stimulation off'. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with 'stimulation on' compared to 'stimulation off' could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program.
KW  - Adult
KW  - Aged
KW  - Antiparkinson Agents: therapeutic use
KW  - Cortical Synchronization: drug effects
KW  - Cortical Synchronization: physiology
KW  - Deep Brain Stimulation: methods
KW  - Evoked Potentials, Motor: physiology
KW  - Female
KW  - Humans
KW  - Levodopa: therapeutic use
KW  - Longitudinal Studies
KW  - Male
KW  - Middle Aged
KW  - Motor Cortex: physiopathology
KW  - Nerve Net: physiopathology
KW  - Neural Pathways: physiopathology
KW  - Parkinson Disease: pathology
KW  - Parkinson Disease: therapy
KW  - Psychomotor Performance: drug effects
KW  - Subthalamus: physiology
KW  - Time Factors
KW  - Treatment Outcome
KW  - Antiparkinson Agents (NLM Chemicals)
KW  - Levodopa (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25558877
C2  - pmc:PMC4408429
DO  - DOI:10.1093/brain/awu380
UR  - https://pub.dzne.de/record/137841
ER  -