Cortico-motor excitability of the lower limb motor representation: a comparative study in Parkinson's disease and healthy controls
Introduction
Recent developments in the pathophysiology of Parkinson's disease (PD) with transcranial magnetic stimulation (TMS) point out to alterations in cortico-spinal excitability as an important feature in this disorder (Cantello et al., 2002, Rothwell, 1999). While reports on changes in the motor threshold have been inconsistent in PD, other indices of cortico-motoneuronal excitability are clearly affected (reviewed in Cantello et al., 2002). For instance, some authors have reported an increase in the size of motor evoked potentials (MEPs) at rest and a reduced ability to facilitate MEPs with active contraction in PD patients (Chen et al., 2001, Valls-Sole et al., 1994); both indicative of an enhanced cortico-spinal excitability. Further evidence of alterations in cortico-spinal excitability in PD has come from studies looking at motor cortical inhibitory phenomena. For example, the shortening of the silent period evoked in small hand muscles by single pulse TMS during active contraction is thought to reflect impaired GABA-ergic inhibition at the cortical level (Cantello et al., 1991, Priori et al., 1994). Similarly, the attenuation of MEPs induced by paired-pulse TMS, which reflect intra-cortical inhibition, is also reduced in PD (Ridding et al., 1995). These findings, taken together, have been interpreted as evidence that the basal ganglia defect in PD can lead to imbalance in favor of disinhibition or hyperexcitability of the cortico-motoneuronal system (Cantello et al., 2002, Rothwell, 1999).
The majority of TMS studies, including those referred to above, have focused on the upper extremity, with the intrinsic hand muscles being the most frequent target. In fact, in a very recent review of TMS applications in PD, Cantello et al. (2002) noted the paucity of information regarding the lower extremity. This contrasts with the wealth of information from electrophysiological studies showing abnormalities in the lower limb interneuronal spinal circuits (e.g. decreased disynaptic reciprocal inhibition and decreased Ib inhibition) in PD (see Valls-Sole (2000) for a recent review). While it has been shown that upper and lower limb motor representations share similar mechanisms in terms of intra-cortical facilitation and inhibition in paired-pulse TMS paradigms (Chen et al., 1998), the two representations differ qualitatively in terms of descending projections. For example, the activation of distal hand muscles is achieved primarily via direct cortico-motoneuronal projections (Maier et al., 1998), whereas recent evidence suggests that cortical activation in thigh muscles is achieved mainly via an indirect route through lumbar pre-motoneurones (Marchand-Pauvert et al., 1999). In the present study, we selected the quadriceps muscle to explore the excitability of the lower limb motor representation using TMS. The goal was to investigate possible changes in the lower limb motor representation by comparing indices of excitability measured at rest and during voluntary activation in patients with PD and healthy controls.
Section snippets
Participants
Participants consisted of 10 patients with PD (mean age±SD, 60.2±7.5 years) and 11 age-matched healthy controls (56.8±7.2 years). In most cases (7/10), healthy controls consisted of the spouse of the patient in the PD group. As a group, the PD patients consisted of mildly to moderately affected individuals with a median duration of disease of 3.5 years (see Table 1 for clinical details). At the time of assessment, all patients were on their regular medication schedule. As well, the main motor
Relaxed motor threshold and MEPs at rest
The mean values of excitability indices derived in each group are summarized in Table 2. In patients, the lower and upper threshold limits determined at rest corresponded, on average, to 50 and 60% of the stimulator output, respectively (Table 2). In controls, the same limits spread in the 60–70% range. Accordingly, the mean motor threshold was found to be significantly lower in patients than in controls (Table 2). Patients also tended to show larger MEPs at rest, but the difference did not
Discussion
In the present study, we compared cortico-motor indices of excitability derived from TMS of the lower limb motor representation in patients with PD and age-matched controls. Although PD patients were mildly affected and tested while ON-medication, several differences emerged when compared to controls: (1) at rest, patients showed lower motor thresholds in the Quad and larger MEPs amplitude; (2) during active contraction , they produced lower levels of MEPs facilitation with respect to baseline
Acknowledgments
The authors wish to thank the Canadian Society for Parkinson (section Ouatouais) for their help with the recruitment of patients and all participants for their time. The authors also thank H. Manning and H. Lacroix for their assistance with data collection and data analysis. We also thank W. Jelley for her help in revising the manuscript in English.
References (18)
- et al.
Transcranial magnetic stimulation and Parkinson's disease
Brain Res Brain Res Rev
(2002) - et al.
Effects of chronic levodopa and pergolide treatment on cortical excitability in patients with Parkinson's disease: a transcranial magnetic stimulation study
Clin Neurophysiol
(2000) Neurophysiological characterizations of parkinsonian syndromes
Neurophysiol Clin
(2000)- et al.
Enhancement of human motor cortex inhibition by the dopamine receptor agonist pergolide: evidence from transcranial magnetic stimulation
Neurosci Lett
(1996) - et al.
Parkinson's disease rigidity: magnetic motor evoked potentials in a small hand muscle
Neurology
(1991) - et al.
Effects of internal globus pallidus stimulation on motor cortex excitability
Neurology
(2001) - et al.
Intracortical inhibition and facilitation in different representations of the human motor cortex
J Neurophysiol
(1998) - et al.
Association between muscle architecture and quadriceps femoris H-reflex
Muscle Nerve
(1994) - et al.
Long-term activity in upper- and lower-limb muscles of humans
J Appl Physiol
(2001)
Cited by (46)
TDCS for parkinson‘s disease disease-related pain: A randomized trial
2024, Clinical NeurophysiologyClinical neurophysiology of Parkinson's disease and parkinsonism
2022, Clinical Neurophysiology PracticeCitation Excerpt :It reflects the excitability of the most sensitive group of neurons in the M1. Although most studies have reported normal RMT in PD (Ridding et al., 1995; MacKinnon et al., 2005; Ni et al., 2013), some studies have found reduced MT in PD (Valls-Sole et al., 1994; Tremblay and Tremblay, 2002). This may relate to factors such as involuntary contractions due to tremors or rigidity, disease severity and use of dopaminergic medications.
Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?
2021, Neurophysiologie CliniqueMotor cortical circuits in Parkinson disease and dystonia
2019, Handbook of Clinical NeurologyBrain imaging of locomotion in neurological conditions
2018, Neurophysiologie Clinique