title: The cerebral oscillatory network of parkinsonian resting tremor.
abstract: Data from experiments in MPTP monkeys as well as from invasive and non-invasive recordings in patients with Parkinson's disease suggest an abnormal synchronization of neuronal activity in the generation of resting tremor in Parkinson's disease. In six patients with tremor-dominant idiopathic Parkinson's disease, we recorded simultaneously surface electromyograms (EMGs) of hand muscles, and brain activity with a whole-head magnetoencephalography (MEG) system. Using a recently developed analysis tool (Dynamic Imaging of Coherent Sources; DICS), we determined cerebro-muscular and cerebro-cerebral coherence as well as the partial coherence between cerebral areas and muscle, and localized coherent sources within the individual MRI scans. The phase lag between the EMG and cerebral activity was determined by means of a Hilbert transform of both signals. After overnight withdrawal from medication, patients showed typical Parkinson's disease resting tremor (4-6 Hz). This tremor was associated with strong coherence between the EMG of forearm muscles and activity in the contralateral primary motor cortex (M1) at tremor frequency but also at double tremor frequency. Phase lags between M1 activity and EMG were between 15 and 25 ms (M1 activity leading) at single, but also at double tremor frequency, corresponding well to the corticomuscular conduction time. Furthermore, significant coherence was observed between M1 and medial wall areas (cingulate/supplementary motor area; CMA/SMA), lateral premotor cortex (PM), diencephalon, secondary somatosensory cortex (SII), posterior parietal cortex (PPC) and the contralateral cerebellum at single tremor and, even stronger at double tremor frequency. Spectra of coherence between thalamic activity and cerebellum as well as several brain areas revealed additional broad peaks around 20 Hz. Power spectral analysis of activity in all central areas indicated the strongest frequency components at double tremor frequency. Partial coherence analysis and the calculation of phase shifts revealed a strong bidirectional coupling between the EMG and diencephalic activity and a direct afferent coupling between the EMG and SII and the PPC. In contrast, the cerebellum, SMA/CMA and PM show little evidence for direct coupling with the peripheral EMG but seem to be connected with the periphery via other cerebral areas (e.g. M1). In summary, our results demonstrate tremor-related oscillatory activity within a cerebral network, with abnormal coupling in a cerebello-diencephalic-cortical loop and cortical motor (M1, SMA/CMA, PM) and sensory (SII, PPC) areas contralateral to the tremor hand. The main frequency of cerebro-cerebral coupling corresponds to double the tremor frequency.
authors.affiliation: Department of Neurology, Heinrich-Heine University, Duesseldorf, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Timmermann
authors.forename: Joachim
authors.initials: J
authors.lastname: Gross
authors.forename: Martin
authors.initials: M
authors.lastname: Dirks
authors.forename: Jens
authors.initials: J
authors.lastname: Volkmann
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Freund
authors.forename: Alfons
authors.initials: A
authors.lastname: Schnitzler
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D002531:Cerebellum / Q000503:physiopathology; D004027:Diencephalon / Q000503:physiopathology; D004576:Electromyography; D005260:Female; D005542:Forearm; D006225:Hand; D006801:Humans; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D013003:Somatosensory Cortex / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000503:physiopathology; D014202:Tremor / Q000503:physiopathology