A direct relationship between oscillatory subthalamic nucleus–cortex coupling and rest tremor in Parkinson’s disease

Abstract

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems.

Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus

“…In contrast, fixed opening or closing of the eyelid evoked by high frequency stimulation was associated with tonic highamplitude EMG activity ( Figure 9C). Spectral analysis of the EMG activity evoked by low frequency stimulation detected several high-power peaks in the 2-20 Hz range (Figure 9D, which is consistent with physiological tremor [38][39][40]. No high-power peaks within this frequency range were detected in the spontaneous activity or in the activity evoked by 180 Hz stimulation ( Figure 9D).…”

“…Fast Fourier Transformations (FFT) of the EMG amplitude RMS data consistently revealed several prominent low-frequency peaks, from ~2-30 Hz, in recordings during low-frequency stimulation but not during high frequency stimulation or no stimulation (see Figure 9). To analyze tremor-like EMG activity, average power within the 2-20 Hz range was calculated and expressed as a percentage of the 2-20 Hz power average without stimulation because this frequency range is consistent with physiological tremor [38][39][40]. All analyses were performed using the statistical software package Statview (SAS Institute, Cary, NC).…”

Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson’s disease

“…This was referred to as 'unevenness of the energy spectrum' (Nutt et al, 2011) and considered as typical feature of freezing phenomena, and therefore constitutes a motor phenomenon different from PD resting or action tremor that generally occurs at a constant and circumscribed frequency (Nutt et al, 2011). Typically, PD tremor also occurs with significant corticomuscular coherence at single and double tremor frequency, which was not observed in our spectral analysis of ULF (Hirschmann et al, 2013;Timmermann et al, 2003). Finally, it should be recognized that the mechanisms on ULF identified here should only carefully be translated to freezing of gait (Barbe et al, 2014).…”

Re-Emergent Tremor: What do we know so Far?

“…Similarly, several neurophysiological techniques, including transcranial magnetic stimulation [16][17][18][19] and local field potentials recording [12,[20][21][22][23], have been used to investigate the pathophysiology of parkinsonian resting tremor. Future MRI and neurophysiological studies are needed to confirm if the same brain circuits underlie RET and resting tremor.…”