Tremor amplitude and tremor frequency variability in Parkinson’s disease is dependent on activity and synchronisation of central oscillators in basal ganglia (original) (raw)
Related papers
2010
Both standard spectral analysis and time-dependent phase correlation techniques were applied to 27 pairs of tremor-related single units in the globus pallidus internus (GPi) and EMG of patients with Parkinson's disease (PD) undergoing stereotactic neurosurgery. Over long time-scales (ϳ60 s), GPi tremorrelated units were statistically coherent with restricted regions of the peripheral musculature displaying tremor. The distribution of pooled coherence across all pairs supports a classification of GPi cell/EMG oscillatory pairs into coherent or noncoherent. Analysis using ϳ2-s sliding windows shows that oscillatory activity in both GPi tremor units and muscles occurs intermittently over time. For brain/muscle pairs that are coherent, there is partial overlap in the times of oscillatory activity but, in most cases, no significant correlation between the times of oscillatory subepisodes in the two signals. Phase locking between coherent pairs occurs transiently; however, the phase delay is similar for different phase-locking subepisodes. Noncoherent pairs also show episodes of transient phase locking, but they occurred less frequently, and no preferred phase delay was seen across subepisodes. Tremor oscillations in pallidum and EMGs are punctuated by phase slips, which were classified as synchronizing or desynchronizing depending on their effect on phase locking. In coherent pairs, the incidence of synchronizing slips is higher than desynchronizing slips, whereas no significant difference was seen for noncoherent pairs. The results of this quantitative characterization of parkinsonian tremor provide a foundation for hypotheses about the structure and dynamical functioning of basal ganglia motor control networks involved in tremor generation.
Synchrony of rest tremor in multiple limbs in Parkinson's disease: evidence for multiple oscillators
Journal of Neural Transmission, 2001
Recent evidence points to involvement of central nervous system oscillators in Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple oscillators cause tremor in multiple limbs. Based on the prediction that multiple oscillators would cause low coherence even with similar average frequency, we studied 22 PD patients using accelerometers on multiple limbs. Records were digitized and spectral analysis was performed. Peak frequencies in the arms, legs, and chin were similar, indicating that biomechanical factors did not determine the frequency. Coherence between different axes of individual accelerometers and between different segments of the same limb was high. However, coherence between tremor in different limbs was low. There was no consistent pattern across patients of ipsi- vs. contralateral predominance of coherence. These data suggest that tremor in PD is generated by multiple oscillatory circuits, which operate on similar frequencies.
Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential Tremor
Journal of Neuroscience, 2015
Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N ϭ 24) and ET (N ϭ 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.
Movement Disorders, 2008
Rhesus and vervet monkeys respond differently to treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia, rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent, short episodes of high-frequency tremor, whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment, the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, cross-correlograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vervet monkey were clustered around 0 phase shift, unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0 degrees and 180 degrees. Analysis of the instantaneous phase differences between tremors of two limbs in the MPTP monkeys and human parkinsonian patients showed short periods of tremor synchronization. We thus concluded that the rhesus and the vervet models of MPTP-induced parkinsonism may represent the tremulous and nontremulous variants of human parkinsonism. We suggest that the tremor phenomena of Parkinson's disease (PD) are related to the emergence of synchronous neuronal oscillations in the basal ganglia. Finally, the oscillating neuronal assemblies in the pallidum of tremulous parkinsonian primates are more stable (in time and in space) than those of parkinsonian primates without overt tremor.
Re-emergent tremor in Parkinson's disease: A clinical and electromyographic study
Journal of the Neurological Sciences, 2016
Re-emergent tremor (RET) and the classical parkinsonian rest tremor were considered as two different phenomena of the same central tremor circuit. However, clinical and accelerometric characteristics of these tremors were not previously compared in a single study. We evaluated disease characteristics and accelerometric measurements of two tremor types in 42 patients with Parkinson's disease. Disease specific features and accelerometric measurements of peak frequency, amplitude at peak frequency and the root mean square (RMS) amplitude of two tremor types were compared. Eighteen patients had RET and the mean latency of the RET was 9.48 (±9.2) s. Groups of only rest tremor and RET did not differ significantly in age of disease onset, disease duration and severity and mean levodopa equivalent dose. Comparison of peak frequency and amplitude at peak frequency were not different between the groups, but RMS amplitude was significantly higher in the RET group (p = 0.03). RMS amplitude of RET was also correlated with disease severity (r = .48, p = 0.04). These results support the previous notion that rest tremor and RET are analogue, both are triggered by the same central ossilator with RET being only the suppression of the rest tremor due to arm repositioning.
Electrophysiologic characteristics of tremor in Parkinson's disease and essential tremor
Arquivos de neuro-psiquiatria, 2014
Tremor in essential tremor (ET) and Parkinson's disease (PD) usually present specific electrophysiologic profiles, however amplitude and frequency may have wide variations. To present the electrophysiologic findings in PD and ET. Patients were assessed at rest, with posture and action. Seventeen patients with ET and 62 with PD were included. PD cases were clustered into three groups: predominant rest tremor; tremor with similar intensity at rest, posture and during kinetic task; and predominant kinetic tremor. Patients with PD presented tremors with average frequency of 5.29±1.18 Hz at rest, 5.79±1.39 Hz with posture and 6.48±1.34 Hz with the kinetic task. Tremor in ET presented with an average frequency of 5.97±1.1 Hz at rest, 6.18±1 Hz with posture and 6.53±1.2 Hz with kinetic task. Seven (41.2%) also showed rest tremor. The tremor analysis alone using the methodology described here, is not sufficient to differentiate tremor in ET and PD.
Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor
Movement Disorders, 2001
Leg tremor during standing is a rare feature in idiopathic Parkinson's disease (PD). Tremor during standing usually has a low frequency (range, 4-6 Hz), similar to PD rest tremor frequency, and is improved by levodopa. We describe three cases of fast orthostatic tremor (FoT) of legs and trunk mimicking primary orthostatic tremor (OT) in patients treated with levodopa for PD. Asymmetrical akinetorigid syndrome was accompanied by a rest tremor in two cases. We obtained electrophysiological parameters by electromyographic (EMG) polygraphic recording after 16 hours withdrawal of antiparkinsonian treatment and at the maximal effect of levodopa in order to investigate the effect of dopaminergic stimulation upon such cases of orthostatic tremor in PD. Electrophysiological parameters of orthostatic tremor, especially frequency (range 14-18 Hz), were similar to that seen in POT. Severity of tremor was independent of seriousness and duration of PD. Levodopa had no effect either on the handicap due to OT or on the amplitude and frequency of the EMG OT activity. In contrast, mild improvement of OT was obtained with benzodiazepines in two cases and parkinsonian syndrome was levodopa-sensitive. These findings suggest that FoT in PD would not be directly controlled by the dopaminergic system. However, increased rhythmicities in basal ganglia or in cerebello-thalamic loops at the rapid frequencies range seen in PD could favor the emergence of a primary orthostatic tremor-like tremor in PD patients.
Characterization of subclinical tremor in Parkinson's disease
Movement Disorders, 2005
The physiological or pathological nature of subclinical tremor amplitude in Parkinson's disease (PD) is not well established. We analyzed characteristics of resting and postural tremors of subclinical amplitude in 17 patients with idiopathic PD without visible resting tremor, having a postural tremor in their least-affected hand rated 0 (12 subjects) or 1 (5 subjects) on Item 21 of the Unified Parkinson's Disease Rating Scale, compared to 17 control subjects matched for age, sex, and handedness. Tremor was recorded at the tip of the index finger using a displacement laser transducer. Overall results show that subclinical resting tremor in PD is significantly different from physiological tremor in terms of amplitude fluctuation, frequency dispersion, harmonic index, and proportional power in 4 to 6 Hz. No significant differences were found for postural tremor. These differences appear to originate mainly from patients with the mixed form of the disease. This study also confirms the preservation of physiological tremor likely originating from a distinct central oscillator in PD. The use of this method in the early and detailed characterization of PD tremors when amplitude is still within normal limits is proposed.