The shape of motor resonance: right- or left-handed?

The human mirror neuron system is a fronto-parietal neural pathway which, when activated by action observation, gives rise to an internal simulation of the observed action (motor resonance). Here we demonstrate how handedness shapes the resonant response, by engaging right-handed (RH) and left-handed (LH) subjects in observation and execution of actions preferentially performed by the dominant hand. We hypothesize that since motor resonance reproduces subliminally the specific motor program for the observed action, it should be subject to motor constraints, such as handedness. A conjunction analysis for observed and executed actions revealed that handedness determines a lateralized activation of the areas engaged in motor resonance. Premotor-BA6 and parietal-BA40 are strongly left lateralized in RH subjects observing or moving their right hand, and to a lesser degree their left hand. Extremely LH subjects show a similar pattern of lateralization on the right, while more ambidextrous LH subjects show a more bilateral activation. The activation of a cortical network outside the mirror neuron system is also discussed.

Bilateral motor resonance evoked by observation of a one-hand movement: role of the primary motor cortex.

In humans, observation of movement performed by others evokes a subliminal motor resonant response, probably mediated by the mirror neurone system, which reproduces the motor commands needed to execute the observed movement with good spatial and temporal fidelity. Motor properties of the resonant response were here investigated with the ultimate goal of understanding the principles operating in the transformation from observation to internal reproduction of movement. Motor resonance was measured as the modulation of excitability of spinal motoneurones, evoked by the observation of a cyclic flexion-extension of one hand. The first two experiments showed that the observation of a one-hand movement always evoked a bimanual resonant response independent of which hand was observed and that these bilateral responses were consistently phase-linked. H-reflexes simultaneously recorded in right and left flexor carpi radialis muscles were always modulated 'in-phase' with each other. The goal of the third experiment was to define the role of primary motor cortex in the bilateral resonant response. Bilateral H-reflexes were recorded during a temporary inactivation induced by transcranial magnetic stimulation over the left cortical hand motor area of observers. The finding that such cortical depression abolished the H-reflex modulation of only the right flexor carpi radialis motoneurones, leaving it unchanged on the left side, suggested that both primary motor areas were activated by the premotor cortex and transmit the resonant activation through crossed corticospinal pathways. The data provide further evidence that the subliminal activation of motor pathways induced by movement observation is organized according to general rules shared with the control of voluntary movement.

Broca's Area as a Pre-articulatory Phonetic Encoder: Gating the Motor Program.

The exact nature of the role of Broca's area in control of speech and whether it is exerted at the cognitive or at the motor level is still debated. Intraoperative evidence of a lack of motor responses to direct electrical stimulation (DES) of Broca's area and the observation that its stimulation induces a "speech arrest" without an apparent effect on the ongoing activity of phono-articulatory muscles, raises the argument. Essentially, attribution of direct involvement of Broca's area in motor control of speech, requires evidence of a functional connection of this area with the phono-articulatory muscles' motoneurons. With a quantitative approach we investigated, in 20 patients undergoing surgery for brain tumors, whether DES delivered on Broca's area affects the recruitment of the phono-articulatory muscles' motor units. The electromyography (EMG) of the muscles active during two speech tasks (object picture naming and counting) was recorded during and in absence of DES on Broca's area. Offline, the EMG of each muscle was analyzed in frequency (power spectrum, PS) and time domain (root mean square, RMS) and the two conditions compared. Results show that DES on Broca's area induces an intensity-dependent "speech arrest." The intensity of DES needed to induce "speech arrest" when applied on Broca's area was higher when compared to the intensity effective on the neighboring pre-motor/motor cortices. Notably, PS and RMS measured on the EMG recorded during "speech arrest" were superimposable to those recorded at baseline. Partial interruptions of speech were not observed. Speech arrest was an "all-or-none" effect: muscle activation started only by removing DES, as if DES prevented speech onset. The same effect was observed when stimulating directly the subcortical fibers running below Broca's area. Intraoperative data point to Broca's area as a functional gate authorizing the phonetic translation to be executed by the motor areas. Given the absence of a direct effect on motor units recruitment, a direct control of Broca's area on the phono-articulatory apparatus seems unlikely. Moreover, the strict correlation between DES-intensity and speech prevention, might attribute this effect to the inactivation of the subcortical fibers rather than to Broca's cortical neurons.

Cyclic time course of motor excitability modulation during the observation of a cyclic hand movement.

The observation of a sinusoidal flexion-extension of the wrist was utilized to determine the continuous time course and phase relation between observed movement and its effects on the observer's motor pathways. While observing movements performed by others, the observers' cortical motor areas and spinal circuits were activated, reflecting the specific temporal and muscular pattern of the actual movement (motor resonance). H-reflexes and motor-evoked potentials (MEPs) were elicited, respectively, by electrical stimulation of the median nerve and magnetic stimulation of the appropriate cortical area, in the right forearm muscle Flexor Carpi Radialis (FCR) of subjects who were observing a 1-Hz cyclic oscillation of the right prone hand executed by a different person. Observation elicited a parallel cyclic excitability modulation of the observer's H-reflex and MEP responses with identical period as the observed movement. Modulation was phase advanced, as is muscle activation with respect to the real movement. The same results were obtained when the observed hand oscillation was executed with different frequency (1.6 Hz) and when the hands of mover and observer were supine. No motor resonance was elicited by observing the oscillation of a metal platform. The excitability modulation of MEPs simultaneously monitored in both antagonists of the observer's forearm (FCR and Extensor Carpi Radialis, ECR) was in almost perfect phase opposition, reflecting their natural reciprocal activation during the execution of a hand oscillation. These findings suggest that during observation, motor pathways are modulated subliminally reproducing with high temporal fidelity the motor commands needed to execute the observed movement.

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.

Patients with primary biliary cirrhosis do not show post-exercise depression of cortical excitability.

OBJECTIVE: Primary biliary cirrhosis (PBC), a female-predominant autoimmune liver disease, is commonly associated with fatigue, a sensation of weariness from physical activity. In healthy subjects, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) increase in amplitude during fatiguing exercise and decrease after the exercise due to post-contraction cortical excitability depression. TMS was utilized herein to investigate if unique cortical excitability changes discriminate women with PBC from healthy controls. METHODS: Twenty-two women (11 with PBC and 11 healthy controls) performed a voluntary submaximal tonic contraction of finger flexor muscles until exhaustion; MEPs were recorded before and during exercise as well as 10min after exercise discontinuation. All subjects completed questionnaires for quality of life and fatigue evaluation. RESULTS: During exercise an increase in MEPs amplitude was observed in all subjects, with no sign of altered peripheral fatigability. Following exercise women with PBC associated with high fatigability showed a significant lack of reduction of MEP size compared to the healthy controls. CONCLUSIONS: Women with PBC do not manifest post-exercise depression of cortical excitability. SIGNIFICANCE: We suggest that an impairment of neural mechanisms underlying physiological central fatigue could occur in PBC, possibly leading to the pathological fatigability lamented by some patients.

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.