Characteristics of Rest and Postural Tremors in Parkinson’s Disease: An Analysis of Motor Unit Firing Synchrony and Patterns

Abstract

The neural mechanisms responsible for resting and postural tremor in Parkinson’s disease (PD) have been the object of considerable study, much of it focusing on supraspinal sites. Here, we adopted an alternative approach that emphasizes motor unit (MU) firing synchrony and patterns of discharge. To explore if these could account for known features of PD tremor, we recorded the instantaneous acceleration of the upper limb of 23 PD patients at rest or while they tried to hold a stable posture together with surface EMG and single MU discharges of upper limb muscles. Spectral, coherence and cross-correlation analyses of the recorded signals demonstrated alternating epoch-I and epoch-II intervals in PD patients both at rest and while they held a stable posture. Epoch-II intervals are characterized by the presence of 4–8 Hz overt tremor, enhanced MU synchrony and spike-doublets or triplets bearing a one-to-one relation to each tremor cycle. Epoch-I resembled physiological tremor in that it was characterized by 6–10 Hz non-overt tremor, lower MU synchrony and rhythmical MU firing at the intrinsic rate of the unit. The frequency of overt and non-overt tremor remained the same whether the patient was at rest or held a stable posture and the same was true of the remaining characteristics of epoch-I and epoch-II. The mean interval between spikes of a doublet/triplet varied between 30 and 50 ms and, for any given patient, remained roughly constant throughout measurements. This is the first time that enhanced MU synchrony and spike doublets/triplets characterized by relatively stable interspike intervals, are shown to accompany the overt tremor of PD patients. To account for our findings we propose that a two-state oscillatory spinal stretch reflex loop generates overt parkinsonian tremor in response to intermittent, descending, relatively high frequency oscillatory signals.

Importance of Maximal Strength and Muscle-Tendon Mechanics for Improving Force Steadiness in Persons with Parkinson’s Disease

“…An additional factor contributing to reduced MVC and force control in persons with PD compared to controls might also arise from sub-optimal neural drive, as evidence in amplified alpha-band coherence [ 36 ], irregular and intermittent [ 37 , 38 ] as well as reduced maximal motor unit discharge rates [ 39 ] and voluntary activation [ 26 , 32 , 33 , 34 ]. These neuromuscular factors can limit force production capacity and control.…”

Tremor in Parkinson’s Disease May Arise from Interactions of Central Rhythms with Spinal Reflex Loop Oscillations

“…In two recent studies, Christakos et al [44] and Agapaki et al [45] investigated motor unit synchrony and firing patterns during force (isometric contractions), postural and resting tremor in a large number of mildly affected patients with tremor dominant PD. The discharges of single motor unit spikes were recorded with needle electrodes inserted into the muscles involved in tremor production.…”

“…Do these repetitive discharges in patients originate from brief augmentations of the motor unit excitatory state? Against this assumption is the experimental finding that the mean short ISI duration was found to be independent from the intrinsic firing rate of the motor unit [45]. Normally, smaller motor units, i.e., those discharging at high rates, are expected to fire at shorter interspike intervals in response to a certain level of impinging excitatory drive than larger units.…”

“…Most importantly, the longer the ISI duration within doublets/triplets, the greater the difference between the overt (epoch-II) and normal-like (epoch-I) tremor frequency was (Fig. 8D in [45]). This key relationship suggested that doublets/triplets may somehow be linked to a mechanism triggering (lower frequency) parkinsonian out of (higher frequency) physiological tremor.…”

“…As the intrinsic motor unit firing rate does not change across transitions from normal-like epoch-I to overt force and postural tremor epoch-II in patients, the question arises whether physiological tremor can be appropriately modulated to parkinsonian tremor by an input impinging intermittently upon motoneurons. Important clues as to how such modulations may come forth, have been yielded by (i) the invariant ("fixed") mean duration of the short ISI within doublets/triplets across recordings in a given patient and (ii) by the fact that the duration of this interval is positively correlated with the difference between overt and normal-like tremor cycle periods [45]. Indeed, motoneurons synchronized by the afferent Ia bursts and at the same time exposed to (relatively weak) synaptic input in the beta-range, may be expected to discharge spikes separated by approximately 40-50 Hz just when they are brought near to threshold through the rhythmical spindle afferent activity (Fig.…”