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.

Highlights

  • Rest tremor is one of the cardinal signs of Parkinson’s disease (PD)

  • Most investigations of Parkinsonian tremor focused on supra-spinal sites and assumed that rhythmical cell activation in these regions at frequencies between 4 and 8 Hz are involved in tremor generation

  • Our main results are: (a) The presence of epoch-II intervals randomly interspersed with epoch-I intervals both at rest and while the patients maintained a stable posture. (b) EpochII intervals are characterized by enhanced motor unit (MU) synchrony at the frequency of the primary component of tremor and spike doublets/triplets exhibiting fixed, beta-range, patient specific, mean short interspike interval (ISI) bearing a one to one relationship to each tremor cycle. (c) Epoch-I intervals are reminiscent of the physiological tremor of normal subjects and are characterized by rhythmical MU firing and weak MU synchrony at the frequency of the secondary component of tremor. (d) The frequency of the primary and secondary components did not change appreciably whether a patient was resting or maintaining a stable posture

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Summary

Introduction

Rest tremor is one of the cardinal signs of PD. Postural tremor is often present as well, both occurring in the 4–8-Hz range (Bain, 2002). Rest tremor, evaluated while patients are asked to relax, has been studied for the most part separately from postural tremor The latter coexists with muscle activity opposing gravity. Other investigations obtained results strongly suggesting the involvement of proprioceptive input and peripheral loops or spinal motor systems in tremor generation (Rack and Ross, 1986; Burne, 1987; Spiegel et al, 2002; Rivlin-Etzion et al, 2008). Hypotheses assuming their supra-spinal origin are far more popular, the neural basis of PD tremor remains unclear

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