Fausto Baldissera

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.

Transplantation of nanostructured composite scaffolds results in the regeneration of chronically injured spinal cords

The destruction and hollowing of entire tissue segments represent an insurmountable barrier to axonal regeneration and therapeutics in chronic spinal cord injury. To circumvent this problem, we engineered neural prosthetics, by assembling electrospun nanofibers and self-assembling peptides into composite guidance channels and transplanted them into the cysts of a postcontusive, chronic spinal cord injury rat model, also providing delivery of proregenerative cytokines. Six months later conspicuous cord reconstruction was observed. The cyst was replaced by newly formed tissue comprising neural and stromal cells. Nerve fibers were interspersed between and inside the guidance channels, spanning the lesion, amidst a well-developed vascular network, basal lamina, and myelin. This was accompanied by a significant improvement in the activity of ascending and descending motor pathways and the global locomotion score. Thus by engineering nanostructured matrices into neuroprosthetics, it is possible to recreate an anatomical, structural, and histological framework, which leads to the replacement of large, hollow tissue gaps in the chronically injured spinal cord, fostering axonal regeneration and neurological recovery.

Excitability changes in human corticospinal projections to muscles moving hand and fingers while viewing a reaching and grasping action

Excitability of the H‐reflex in the relaxed flexor digitorum superficialis (FDS) muscle was tested in five subjects observing a reaching and grasping action. The amplitude of the FDS H‐reflex was modulated with a peak occurring during the hand‐opening phase of the observed movement. When the H‐reflex was facilitated by subliminal transcranial magnetic stimulation (TMS), the modulation was larger than for an unconditioned reflex of similar size. This suggests that the primary motor cortex excitability is modulated by action viewing and reasonably causes the motoneuronal excitability changes. Moreover, motor evoked potentials (MEPs) were elicited by supraliminal TMS in FDS, flexor carpi radialis (FCR) and first dorsal interosseus (FDI) when observing the same movement. MEP amplitude was modulated in FDS with the same time‐course as the H‐reflex, the peak excitability occurring during hand opening. In FDI, however, the maximal excitability occurred during finger closing while in FCR no correlation was found with the movement phases. Finally the EMG activity of FCR, FDS and FDI was recorded while the subjects were actually performing a grasping movement similar to the one observed. In all subjects and for each muscle there was a clear‐cut correspondence between the time‐course of the excitability modulation of MEPs and the temporal pattern of EMG recruitment. In conclusion, the present study suggests that ‘motor resonance’ subliminally activates the same motor pathways that would be overtly recruited in each observer when actually performing the observed movement, reproducing the personal strategy adopted in the same task.

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.

Activation of motor pathways during observation and execution of hand movements

Abstract Some neural properties of “motor resonance”—the subliminal activation of the motor system when observing actions performed by others—are investigated in humans. Two actions performed with the right hand are observed by experimental subjects: a finalized (transitive) action (reaching for and grasping a ball) and an intransitive action (cyclic up-and-down oscillation of the hand), while the H-reflex and Transcranial Magnetic Stimulation techniques are utilized to test the excitability of the observers motor pathways to hand and forearm muscles (first dorsal interosseus, flexor digitorum superficialis, flexor carpi radialis). Results indicate that motor resonance: (1) is mainly mediated by the primary motor cortex; (2) involves the same forearm muscles as used in the execution of the observed movement; (3) is also recorded in the homologous muscles of the arm contralateral to the one observed; and (4) is evoked by both transitive and intransitive movements of the human hand, but not by similar movements of inanimate objects. The similarities and discrepancies between the resonant response in humans and the properties of monkey “mirror neurons” are discussed.

Excitability changes in resting forearm muscles during voluntary foot movements depend on hand position: a neural substrate for hand-foot isodirectional coupling

When associating hand and foot voluntary oscillations, isodirectional coupling is preferred irrespective of hand position (prone or supine). To investigate the neural correlates of this coupling modality, excitability of the motor projections innervating the resting forearm was tested during cyclic voluntary flexion-extensions of the ipsilateral foot. H-reflexes, in some experiments facilitated by subliminal Transcranial Magnetic Stimulation (TMS), and Compound Muscle Action Potentials (CMAPs), evoked by supraliminal TMS, were elicited in Flexor Carpi Radialis (FCR) and Extensor Carpi Radialis (ECR) muscles at five intervals during the foot movement cycle. With the hand prone, a sinusoidal excitability modulation was observed in wrist flexors and extensors, but reversed in phase: in FCR, excitability increased during plantar-flexion and decreased during dorsiflexion, while in ECR the opposite occurred. This reciprocal organisation was confirmed by the excitability modulation of CMAPs evoked simultaneously in the two antagonists. When the hand was supinated, the H-reflex modulation reversed in phase, i.e., FCR excitability increased during foot dorsiflexion and decreased during plantar-flexion. In both muscles and hand positions tested, when the muscle-to-movement phase-lag was increased by inertial loading of the foot, H-reflex excitability modulations remained phase linked to muscular contractions, not to movement. Together, these results suggest that the subliminal excitability modulation of hand movers has a common central origin with the parallel overt activation of foot movers, is reciprocally organised, and is direction- not muscle-dependent. It may therefore represent the neural substrate for isodirectional coupling of hand (prone or supine) with the foot.

Cyclic modulation of the H-reflex in a wrist flexor during rhythmic flexion-extension movements of the ipsilateral foot.

Abstract In 12 subjects, each sitting on an armchair with the right forearm prone, the H-reflex elicited in the resting flexor carpi radialis muscle underwent cyclic excitability changes correlated with rhythmic flexion-extension movements of the ipsilateral foot (frequency of oscillations between 1.5 and 2.5 Hz). During foot plantar flexion, the H-reflex underwent a clear-cut increase, the maximum facilitation falling, in most subjects, within the second half of that phase; then, a gradual reduction in size led the reflex amplitude back to the initial value at the end of foot dorsal extension. If present also when the wrist and the ankle are moved together, this facilitation should favour the in-phase (isodirectional) association between movements and, conversely, hinder the anti-phase coupling.

Depolarization of trigeminal afferents induced by stimulation of brain-stem and peripheral nerves

Summary1.In nembutalized cats the excitability of supraorbital (SO) and infraorbital (IO) primary afferents was tested by microelectrode stimulation within the trigeminal nuclei. SO excitability increased after conditioning stimulation of IO nerve, brain-stem throughout its extent and ipsi- and contralateral fore- and hindlimb nerves. The conditioning curves did not change in decerebrate preparations.2.In decerebrate cats a negative slow potential (trigeminal dorsal root potential, TDRP) was recorded from the isolated sensory trigeminal root following stimulation of contralateral SO nerve, homolateral common radial trunk and brain-stem.3.In nembutalized as in decerebrate cats, a single IO impulse induced in the trigeminal complex a focal synaptic potential (N1-N2-waves) followed by a prolonged (200 msec) slow potential (P-wave). P-waves were also produced by high frequency stimulation of the brain-stem reticular regions. They were positive laterally to the trigeminal nucleus and inverted along a line between nucleus and tract. The N-wave had maximal amplitude in the trigeminal nucleus and became positive at the level of its medial boundary.4.Unit discharges in the trigeminal nucleus responding to IO volley and lemniscal potentials evoked by the same stimulus were depressed by reticular activation following a time course of over 100 msec.5.The results suggest a process of primary afferent depolarization (PAD), of trigeminal fibers induced by stimulations of brain-stem, fore- and hind-limbs nerves and other trigeminal afferents in absence of forebrain and cortical structures.

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.