Paolo Cavallari

Modulation of spinal excitability during observation of hand actions in humans.

There is growing evidence that observation of actions performed by other individuals activates observers cortical motor areas. This matching of observed actions on the observers motor repertoire could be at the basis of action recognition. Here we investigated if action observation, in addition to cortical motor areas, involves also low level motor structures mimicking the observed actions as if they were performed by the observer. Spinal cord excitability was tested by eliciting the H‐reflex in a finger flexor muscle (flexor digitorum superficialis) in humans looking at goal‐directed hand actions presented on a TV screen. We found that, in the absence of any detectable muscle activity, there was in the observers a significant modulation of the monosynaptic reflex size, specifically related to the different phases of the observed movement. The recorded H‐reflex rapidly increased in size during hand opening, it was depressed during hand closing and quickly recovered during object lifting. This modulation pattern is, however, opposite to that occurring when the recorded muscles are actually executing the observed action [Lemon et al. (1995) J. Neurosci., 15, 6145–56]. Considering that, when investigated at cortical level the modulation pattern of corticospinal excitability replicates the observed movements [Fadiga et al. (1995) J. Neurophysiol., 73, 2608–2611], this spinal ‘inverted mirror’ behaviour might be finalised to prevent the overt replica of the seen action.

Differential control of in-phase and anti-phase coupling of rhythmic movements of ipsilateral hand and foot.

SummaryRhythmic flexion-extensions of ipsilateral hand and foot are easily performed (“easy” association) when the two segments are moved in phase (isodirectionally), whereas great care and attention are required (“difficult” association) to move them in phase opposition. We searched for features distinguishing the two types of coupling by analyzing, on ten subjects: 1) the frequency limit in each association; and, 2) if coupling is modified by inertial or elastic loading of the hand. 1) Subjects were asked to oscillate hand and foot at various paced frequencies, in the easy or in the difficult association for one minute at least. In the easy coupling, the task was performed up to 2.0–2.5 Hz, the duration being thereafter shortened by muscular fatigue. In the difficult coupling when the frequency was increased above 0.7–1.7 Hz, the performance rapidly shortened, not because of fatigue but because of an inevitable reversal to the in-phase movement. The frequency-duration curve always followed a similar decay, although it covered different frequency ranges in the various subjects. 2) The effect of charging the hand with inertial or elastic loads was studied at the subjects preferred frequency, chosen when the hand was unloaded. Without loading, in the easy association the hand cycle slightly lagged the foot cycle while in the difficult one an almost perfect phase opposition was maintained. Under inertial load (inertial momentum: 9 gm2), in the easy association the hand lag was increased by 10° to 45°, despite a compensatory advanced activation of the forearm EMG; in the difficult association, instead, the hand lag was small (less than 10°), thanks to an even earlier onset of the forearm EMG. The elastic load (torque: 4 gm) had negligible effects on the phase relation between movements but improved the phase relation between EMGs. These findings show that coupling is tighter in the difficult than in the easy association, a feature that is emphasized by the effect of the load. This supports the idea that kinaesthetic afferences have more pronounced influences on control of the anti-phase than the in-phase coupling.

Excitability changes in human corticospinal projections to forearm muscles during voluntary movement of ipsilateral foot

Excitability of the H‐reflex in the relaxed flexor carpi radialis (FCR) muscle was tested during voluntary oscillations of the ipsilateral foot at five evenly spaced delays during a 600 ms cycle. In some experiments the H‐reflex was conditioned by transcranial magnetic stimulation (TMS). With the hand prone, the amplitude of the FCR H‐reflex was modulated sinusoidally with the same period as the foot oscillation, the modulation peak occurring in coincidence with contraction of the foot plantar‐flexor soleus and the trough during contraction of the extensor tibialis anterior. When the H‐reflex was facilitated by TMS at short latency (conditioning‐test interval: −2 to −3.5 ms), the modulation was larger than that occurring with an unconditioned reflex of comparable size. This suggests that both the peripheral and the corticospinal components of the facilitated response were modulated in parallel. When the H‐reflex was tested 40–60 ms after conditioning, i.e. during the cortical ‘silent period’ induced by TMS, no direct effect was produced on the reflex size but the foot‐associated modulation was deeply depressed. These results suggest that the reflex modulation may depend on activity fluctuations in the cortical motor area innervating the forearm motoneurones. It is proposed that when the foot is rhythmically oscillated, along with the full activation of the foot cortical area a simultaneous lesser co‐activation of the forearm area produces a subliminal cyclic modulation of cervical motoneurones excitability. Should the two limbs be moved together, the time course of this modulation would favour isodirectional movements of the prone hand and foot, indeed the preferential coupling observed when hand and foot are voluntarily oscillated.

Evidence for mutual inhibition of opposite Ia interneurones in the human upper limb.

SummaryThe H-reflex technique was used to collect indirect evidence for changes in excitability of the interneurones mediating reciprocal Ia inhibition between wrist extensors and flexors. Stimulating the radial nerve results in an inhibition of the flexor carpi radialis (FCR) H-reflex and evidence has previously been presented that the early phase of inhibition is mediated by extensor-coupled Ia interneurones (Ext Ia INs), i.e. by inhibitory interneurones fed by muscle spindle Ia afferents from wrist extensors. Variations in the level of this inhibition were used to assess changes in excitability of Ext Ia INs. Stimulation of group I fibres from flexors was shown to depress the “reference” Ia inhibition, i.e. to inhibit the Ext Ia INs. The central latency of this interneuronal inhibition was compatible with a disynaptic linkage between flexor Ia afferents and Ext Ia INs. Its threshold and time course profile could almost exactly be superimposed on those of reciprocal Ia inhibition from flexors to extensor carpi radialis (ECR) motoneurones (MNs). This suggests that the Ia inhibitions to extensor MNs and extensor Ia INs are collateral effects mediated by the same flexor-coupled Ia interneurones. In two subjects, in whom it was possible to elicit an H-reflex in the ECR, inhibition of flexor-coupled Ia interneurones by activation of extensor Ia interneurones could similarly be demonstrated.

Mediation of late excitation from human hand muscles via parallel group II spinal and group I transcortical pathways

This study addresses the question of the origin of the long‐latency responses evoked in flexors in the forearm by afferents from human hand muscles. The effects of electrical stimuli to the ulnar nerve at wrist level were assessed in healthy subjects using post‐stimulus time histograms for flexor digitorum superficialis and flexor carpi radialis (FCR) single motor units (eight subjects) and the modulation of the ongoing rectified FCR EMG (19 subjects). Ulnar stimulation evoked four successive peaks of heteronymous excitation that were not produced by purely cutaneous stimuli: a monosynaptic Ia excitation, a second group I excitation attributable to a propriospinally mediated effect, and two late peaks. The first long‐latency excitation occurred 8–13 ms after monosynaptic latency and had a high‐threshold (1.2–1.5 × motor threshold). When the conditioning stimulation was applied at a more distal site and when the ulnar nerve was cooled, the latency of this late excitation increased more than the latency of monosynaptic Ia excitation. This late response was not evoked in the contralateral FCR of one patient with bilateral corticospinal projections to FCR motoneurones. Finally, oral tizanidine suppressed the long‐latency high‐threshold excitation but not the early low‐threshold group I responses. These results suggest that the late high‐threshold response is mediated through a spinal pathway fed by muscle spindle group II afferents. The second long‐latency excitation, less frequently observed (but probably underestimated), occurred 16–18 ms after monosynaptic latency, had a low threshold indicating a group I effect, and was not suppressed by tizanidine. It is suggested that this latest excitation involves a transcortical pathway.

Motoneuronal pre‐compensation for the low‐pass filter characteristics of muscle. A quantitative appraisal in cat muscle units

1 The relevance of motoneurone dynamic sensitivity in compensating for the low‐pass filter properties of muscle was assessed by stimulating cat muscle units (MUs) with impulse discharges generated by two current‐to‐rate converters: (i) a spinal motoneurone, sensitive to both the input intensity and its first derivative, and (ii) a linear current‐to‐rate converter, i.e. a neurone model with the same static sensitivity as the motoneurone but lacking dynamic sensitivity. 2 Discharges generated by injection of sine‐wave currents in three motoneurones of the ‘fast’ type and in the three related model versions were applied to the axon of forty‐six MUs. The MU isometric tension was modulated at the frequency of the current sine wave (0.5‐20 Hz). Phase and gain of the current‐to‐force transduction were measured. 3 When MUs were driven by the model, the force lagged the current by 90 deg at 1 Hz in slow MUs and at around 5 Hz in fast MUs. Under motoneurone drive, the 90 deg phase lag was attained at frequencies about twice as high. 4 The gain of the transduction (peak‐to‐peak force modulation/peak‐to‐peak current modulation) decayed when the modulation frequency was increased. In all but five units, the cut‐off frequency, Fco (gain attenuated by −3 dB), was higher when the unit was motoneurone driven (FcoCell) then when it was model driven (FcoMod). In both conditions, Fco was inversely correlated with the MUs time‐to‐peak. The advantage conferred by the motoneurone dynamic sensitivity was expressed by the Fco ratio (FcoCell/FcoMod). Across the MU population this ratio ranged from 0.6‐2.8, was inversely correlated with the time‐to peak, and was directly correlated with the half‐tension rate, i.e. the impulse rate at which MUs develop 50 % of their maximal tetanic force. The largest improvement (Fco ratio > 2.0) was found in units with mechanical features similar to those presumably coupled ‘in vivo’ to the motoneurones utilized for stimulation. 5 This estimate was confirmed in experiments in which trains of pulses, generated by injection of ramp currents in another motoneurone and the related model, were used to activate eight MUs, selected for being similar to that connected ‘in vivo’ to the motoneurone. As expected, for any given current slope the rising phase of isometric tension was steeper when units were motoneurone driven than when they were model driven. The gain (force slope/current slope) was plotted against the ramp slope to identify the cut‐off slope, Sco, at which the gain was attenuated by −3 dB. In this homogeneous MU sample, the ratio expressing the advantage of the motoneurone drive (ScoCell/ScoMod, equivalent to the Fco ratio), ranged from 2.62‐2.97, values comparable with those observed in sine‐wave experiments when the motoneurone and muscle units were properly matched.

Coordination of Cyclic Coupled Movements of Hand and Foot in Normal Subjects and on the Healthy Side of Hemiplegic Patients

Publisher Summary This chapter discusses the coordination of cyclic coupled movements of hand and foot in normal subjects and on the healthy side of hemiplegic patients. Several common life gestures combine movements of different limb segments. When a subject with the hand prone is asked to perform coupled flexion–extension of the hand and foot in a way he feels is easy and spontaneous, he automatically associates the hand extension with the foot dorsal flexion and the hand flexion with the foot plantar flexion. It is reasonable to believe that kinesthetic afferences generated by the ongoing movements are utilized for controlling the synchronism between the hand and foot oscillations. The frequency-related phase changes occurring in the easy association as a consequence of loading and, conversely, the strict maintenance of the anti-phase relation in the difficult coupling notwithstanding the loads should rest on variations of the muscular drive.

Effects of transmastoid electrical stimulation on the triceps brachii EMG in man.

Transmastoid galvanic stimulation was applied to five subjects while records were taken of the rectified and averaged EMG from the triceps brachii of both sides. In four subjects current pulses of 1.6 mA, lasting 10-100 ms, evoked an excitatory response with a latency of 30-35 ms from the side ipsilateral to the anode and inhibition appeared at 40 ms on the side ipsilateral to the cathode. In the fifth subject the stimulus evoked inhibition at 40 ms on both sides. Thresholds for both excitatory and inhibitory responses were between 0.6 and 1 mA. Control experiments excluded a possible cutaneous origin. These actions might therefore represent reflex responses elicited by activation of the vestibular systems.

A role for locus coeruleus in Parkinson tremor

We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.

Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson disease

BackgroundStudies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. Little is known however, about the functional state of the LC in patients with Parkinson disease (PD).MethodsWe retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane). FP-CIT binding values from the patients were compared with 15 healthy subjects: using both a voxel-based whole brain analysis and a volume of interest analysis of a priori defined brain regions.ResultsAverage FP-CIT binding in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p < 0.001). In contrast, subjects with PD showed an increased binding in the LC (166% on average; p < 0.001) in both analyses. LC-binding correlated negatively with striatal FP-CIT binding values (caudate: contralateral, ρ = -0.28, p < 0.01 and ipsilateral ρ = -0.26, p < 0.01; putamen: contralateral, ρ = -0.29, p < 0.01 and ipsilateral ρ = -0.29, p < 0.01).ConclusionsThese findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with early stage PD, compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections.