Original articleExcitability of the lower-limb area of the motor cortex in Parkinson's diseaseExcitabilité des aires motrices corticales des membres inférieurs dans la maladie de Parkinson
Introduction
According to physiological modelling [1] and due to its interposition between altered basal ganglia networks and the intact corticospinal tract [13], the motor cortex is functionally involved in the pathophysiology of Parkinson's disease (PD). Imaging studies have highlighted hypoactivity in the supplementary motor area (SMA) and dorsolateral prefrontal cortex (DLPFC) [35], [41], [19], and hyperactivity in the primary motor cortex (M1), lateral premotor cortex, cerebellum, parietal and occipital lobes [17], [43].
Cortical areas have also been investigated using transcranial magnetic stimulation (TMS). Despite some discrepancies, TMS data in PD disclosed an imbalance of cortical excitability towards a state of reduced inhibition, inducing a cortico-motoneuronal hyperexcitability [10]. In this regard, observations of a reduced resting motor threshold (RMT) [9], decreased cortical silent period (CSP), enhanced amplitude of the motor evoked potential (MEP) with target muscle at rest [20], and impaired short-interval intracortical inhibition (SICI) [37], [33] are particularly relevant. Facilitatory intracortical processes were also found to malfunction, as PD patients exhibited both a reduced MEP amplitude during voluntary contraction [48] and an impaired intracortical facilitation (ICF) [4]. Antiparkinsonian treatments including dopaminergic substitution therapy (DST), subthalamic nucleus stimulation, and repetitive TMS tend to normalize these electrophysiological abnormalities [10], [22]. DST mainly acts on inhibitory processes, lengthening the CSP duration [37], [34] and restoring the SICI [33]. Imaging studies confirmed this by showing the reduction of primary motor cortex hyperactivity under DST [19].
Most of these studies investigated the upper-limb motor cortical area. According to a few TMS studies exploring leg muscles of normal subjects, upper- and lower-limb cortical motor areas seem to share similar intracortical mechanisms [12]. However, imaging data indicated that their cortical activation patterns are quite different [31], [26], [42]. Indeed, hands are most of the time required for volitional or visuo-guided movements whereas lower limbs are rather implied in automatic and self-generated movements. Therefore, it is likely that these two kinds of movement differently recruit the central nervous system [29], [18], [3]. PD primarily affects automatic movements [28] and, particularly, the gait pattern, with a reduction of walking speed and amplitude of leg movements, giving rise to the characteristic small and shuffling steps, sometimes with freezing [5]. Only one single-pulse TMS study explored a proximal lower-limb muscle in PD patients and found similar abnormalities as those described with hand muscles [46]. In our study, we completed the investigation with a paired-pulse study of lower-limb cortical motor areas. We chose to explore the tibialis anterior (TA) muscle, owing to its key role in gait [13], [11].
Section snippets
Subjects
This study was carried out on 24 PD patients (three women, 62 ± 7 years) and nine control subjects (four women, 60 ± 4 years). All the patients were candidates for deep brain stimulation and were therefore very doparesponsive (see Table 1 for clinical details). Their clinical examination was performed in the early morning by the same expert in movement disorders after an overnight DST withdrawal (OFF condition). Their usual DST including L-Dopa and short-acting dopaminergic agonists (no long
TMS of lower limbs
RMT and AMT did not differ between groups (PD OFF, PD ON and controls). In each group, AMT was significantly smaller than RMT (p < 0.001) (Table 2).
MEP amplitudes did not differ significantly between groups at rest nor during 20% contraction of the TA. The facilitating effect of the volitional contraction on MEP amplitude and area was significant (p < 0.05), whatever the group. There were no significant between-group differences in the mean CSP duration.
With the paired-pulse paradigm (Fig. 1),
Discussion
Our study demonstrates that, in PD patients, an impairment of ICF may occur in cortical areas of distal lower-limb muscles while SICI seemed to be preserved. This is at odds with studies investigating upper-limb areas, which demonstrated a deficit of inhibitory phenomenon [10].
In keeping with the literature, paired-pulse paradigms appeared to be the most sensitive tool to highlight cortical abnormalities in PD [15], [21] but these were not used in the single previous study on lower limb in PD
Conflicts of interest
None to be declare.
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