The pathophysiology of parkinsonian tremor: a review

Abstract

Parkinsonian tremor is most likely due to oscillating neuronal activity within the CNS. Summarizing all the available evidence, peripheral factors only play a minor role in the generation, maintenance and modulation of PD tremor. Recent studies have shown that not a single but multiple oscillators are responsible. The most likely candidate producing these oscillations is the basal ganglia loop and its topographic organization might be responsible for the separation into different oscillators which, nevertheless, usually produce the same frequency. The neuronal mechanisms underlying these oscillations are not yet clear, but three hypotheses would be compatible with the presently available data from animal models and data recorded in patients. The first is a cortico-subthalamo-pallido-thalamic loop, the second is a pacemaker consisting of the external pallidum and the subthalamic nucleus, and the third is abnormal synchronization due to unknown mechanisms within the whole striato-pallido-thalamic pathway leading to a loss of segregation. Assuming the oscillator within the basal ganglia pathway, the mechanism of stereotactic surgery might be a desynchronization of the activity of the basal ganglia-thalamo-cortical or the cerebello-thalamo-cortical pathway.

Morphological differences in Parkinson’s disease with and without rest tremor

“…This prospective study using high-resolution MRI VBM to compare brain morphology of the different motor phenotypes of PD demonstrates for the first time a structural abnormality in the cerebellum in PD with rest tremor and highlights the postulated cerebellar involvement in the pathogenesis of rest tremor [16,42,61]. Rest tremor has been shown to correlate with increased metabolic [3,15,22] and oscillatory activity [64] in the cerebellum, thalamus and motor cortex.…”

“…The thalamic targets, Vim [5,10,44,46,47] and the cerebello-thalamic projections [11], have proven efficacious in the suppression of rest tremor and Vim was even postulated to a better target than the ventro-oralis posterior nucleus (Vop) receiving pallidal afferents [61]. The fact that Vim receives cerebellar afferents, but none from the basal ganglia [34], implies that rest tremor originates from either a cerebellar generator [61] or an interaction of the basal ganglia-and cerebellothalamo-cortical circuits in the cerebral cortex, where those segregated circuits converge [16].…”

“…Based on current understanding of tremor pathogenesis [16,42,61], we predicted structural changes in the basal ganglia, the thalamus, the brainstem and/or the cerebellum (R BG-thalamus-brainstem-cerebellum ), and, therefore, restricted the statistical analysis to these regions applying a mask of these regions to the grey matter volume distribution maps prior to statistical analysis.…”

“…Nigro-striatal dopamine deficiency correlates best with bradykinesia, but not with tremor [65]. Oscillating neurons in one or multiple localizations within the basal ganglia-thalamo-cortical loop may cause rest tremor, and an active contribution of the cerebellum and the cerebello-thalamo-cortical projections has been postulated [16,42,61].…”

Quality parameters for a multimodal EEG/EMG/kinematic brain-computer interface (BCI) aiming to suppress neurological tremor in upper limbs

“…Assessments of kinematic data per se are particularly interesting because of their simplicity and their direct access without intrusion in the body. Three main neuronal mechanisms have been hypothesized for rest tremor: a cortico-subthalamo-pallido-thalamic loop generating tremor, a pacemaker consisting of the external pallidum and the subthalamic nucleus, and an abnormal synchronization within the whole striato-pallido-thalamic pathway leading to a loss of segregation 16 . The findings of a decrement of rest tremor before voluntary movement in Parkinson’s disease patients suggest an involvement of a neuronal input from the cerebellum to the thalamus, which may occur sufficiently early to suppress the resting tremor before the voluntary movement 8 .…”