Cortical correlates of the basic and first harmonic frequency of Parkinsonian tremor Jan Raethjen * , R.B. Govindan, M. Muthuraman, Florian Kopper, Jens Volkmann, Günther Deuschl Dept. of Neurology, University of Kiel, Schittenhelmstr. 10, 24105 Kiel, Germany See Editorial, pages 1766–1767 article info Article history: Accepted 3 June 2009 Available online 12 September 2009 Keywords: Parkinson’s disease Tremor EEG EMG Corticomuscular coherence Delay First harmonic abstract Objective: It has been hypothesized that the basic and first harmonic frequency of Parkinsonian tremor are somewhat independent oscillations the biological basis of which remains unclear. Methods: We recorded 64-channel EEG in parallel with EMG of the forearm muscles most affected by rest tremor in 21 PD patients. EMG power spectrum, corticomuscular coherence spectra and EEG power spec- tra for each EEG electrode were calculated. The dynamics of the coherence and relative EMG and EEG power at the basic (tremor) frequency were calculated by a sliding, overlapping window analysis. Corti- comuscular delays and direction of interaction were analysed by the maximizing coherence method for narrow band signals. Results: The contralateral EEG electrodes with maximal coherence were different for the basic and first harmonic frequency. The dynamical coherence curves showed non-parallel time courses for the two fre- quencies. The mean EEG-EMG and EMG-EEG delays were all around 15–20 ms but significantly longer for the first harmonic than for the basic frequency. Conclusions: Our data indicate different cortical representations and corticomuscular interaction of the basic and first harmonic frequencies of Parkinsonian tremor. Significance: Separate central generators seem to contribute to the tremor via different pathways. Further studies on this complex tremor network are warranted. Ó 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Classical Parkinsonian resting tremor is very regular with a typ- ical frequency between 3 and 6 Hz. However, in the power spec- trum of the underlying rhythmic muscle activity we typically find a peak not only at the tremor frequency but also at double this frequency (Spieker et al., 1995; Deuschl et al., 1996; Milanov, 2000). This higher frequency peak is termed first higher harmonic, as it is a well known physical phenomenon that rhythmic pro- cesses with nonlinear or asymmetric wave forms produce peaks not only at their actual frequency (basic frequency) but also har- monic peaks at integer multiples of the basic frequency (Deuschl et al., 2000). In such cases the higher harmonic peaks can be con- sidered to reflect a part of the same rhythmic process at the basic frequency. As wave form analyses have shown asymmetries in Par- kinsonian tremor (Deuschl et al., 1995) its first higher harmonic peak has usually been interpreted in line with this physical rule. But this interpretation has been questioned recently. On the basis of MEG–EMG analyses it has been postulated that the first higher harmonic is the main corticospinal drive contributing to the peripheral tremor (Timmermann et al., 2003). A recent analysis in the time domain has lent further support to the view that the first harmonic peak may reflect an independent phenomenon (Sa- pir et al., 2003) rather than a mere effect of wave form asymmetry. However, the biological basis of such independent oscillations in Parkinsonian tremor remains obscure. One possible explanation would be separate central (cortical) generators as has been alluded to by (Volkmann et al., 1996). If this assumption was correct one would expect differing temporal and spatial patterns of the cortical correlates of the basic and higher harmonic frequencies in Parkinsonian tremor. We therefore examined the corticomuscular (EEG-EMG) coherence in such patients specifically looking for differences in the distribution of the coherences on the scalp and in their dynamics over time. 2. Methods 2.1. Patients Twenty-one patients, 10 female and 11 male, were included in the study all of which fulfilled the diagnostic brain bank criteria for 1388-2457/$36.00 Ó 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2009.06.028 * Corresponding author. Tel.: +49 (0)431 597 8515; fax: +49 (0)431 597 8502. E-mail address: j.raethjen@neurologie.uni-kiel.de (J. Raethjen). Clinical Neurophysiology 120 (2009) 1866–1872 Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph