Does the Motor Cortex Want the Full Story? The Influence of Sentence Context on Corticospinal Excitability in Action Language Processing.

The reading of action verbs has been shown to activate motor areas, whereby sentence context may serve to either globally strengthen this activation or to selectively sharpen it. To investigate this issue, we manipulated the presence of manual actions and sentence context, assessing the level of corticospinal excitability by means of transcranial magnetic stimulation. We hypothesized that context would serve to sharpen the neural representation of the described actions in the motor cortex, reflected in context-specific modulation of corticospinal excitability. Participants silently read manual action verbs and non-manual verbs, preceded by a full sentence (rich context) or not (minimal context). Transcranial magnetic stimulation pulses were delivered at rest or shortly after verb presentation. The coil was positioned over the cortical representation of the right first dorsal interosseous (pointer finger). We observed a general increase of corticospinal excitability while reading both manual action and non-manual verbs in minimal context, whereas the modulation was action-specific in rich context: corticospinal excitability increased while reading manual verbs, but did not differ from baseline for non-manual verbs. These findings suggest that sentence context sharpens motor representations, activating the motor cortex when relevant and eliminating any residual motor activation when no action is present.

Motor imagery helps updating internal models during microgravity exposure.

Skilled movements result from a mixture of feedforward and feedback mechanisms conceptualized by internal models. These mechanisms subserve both motor execution and motor imagery. Current research suggests that imagery allows updating feedforward mechanisms, leading to better performance in familiar contexts. Does this still hold in radically new contexts? Here, we test this ability by asking participants to imagine swinging arm movements around shoulder in normal gravity condition and in microgravity in which studies showed that movements slow down. We timed several cycles of actual and imagined arm pendular movements in three groups of subjects during parabolic flight campaign. The first, control, group remained on the ground. The second group was exposed to microgravity but did not imagine movements inflight. The third group was exposed to microgravity and imagined movements inflight. All groups performed and imagined the movements before and after the flight. We predicted that a mere exposure to microgravity would induce changes in imagined movement duration. We found this held true for the group who imagined the movements, suggesting an update of internal representations of gravity. However, we did not find a similar effect in the group exposed to microgravity despite the fact that the participants lived the same gravitational variations as the first group. Overall, these results suggest that motor imagery contributes to update internal representations of the considered movement in unfamiliar environments, while a mere exposure proved to be insufficient.NEW & NOTEWORTHY Gravity strongly affects the way movements are performed. How internal models process this information to adapt behavior to novel contexts is still unknown. The microgravity environment itself does not provide enough information to optimally adjust the period of natural arm swinging movements to microgravity. However, motor imagery of the task while immersed in microgravity was sufficient to update internal models. These results show that actually executing a task is not necessary to update graviception.

Corticospinal and Spinal Excitabilities Are Modulated during Motor Imagery Associated with Somatosensory Electrical Nerve Stimulation.

Motor imagery (MI), the mental simulation of an action, influences the cortical, corticospinal, and spinal levels, despite the lack of somatosensory afferent feedbacks. The aim of this study was to analyze the effect of MI associated with somatosensory stimulation (SS) on the corticospinal and spinal excitabilities. We used transcranial magnetic stimulation and peripheral nerve stimulation to induce motor-evoked potentials (MEP) and H-reflexes, respectively, in soleus and medialis gastrocnemius (MG) muscles of the right leg. Twelve participants performed three tasks: (1) MI of submaximal plantar flexion, (2) SS at 65 Hz on the posterior tibial nerve with an intensity below the motor threshold, and (3) MI + SS. MEP and H-reflex amplitudes were recorded before, during, and after the tasks. Our results confirmed that MI increased corticospinal excitability in a time-specific manner. We found that MI + SS tended to potentiate MEP amplitude of the MG muscle compared to MI alone. We confirmed that SS decreased spinal excitability, and this decrease was partially compensated when combined with MI, especially for the MG muscle. The increase of CSE could be explained by a modulation of the spinal inhibitions induced by SS, depending on the amount of afferent feedbacks.

Effect of mental fatigue on speed-accuracy trade-off.

The aim of this study was to investigate the effects of mental fatigue on the duration of actual and imagined goal-directed arm movements involving speed-accuracy trade-off. Ten participants performed actual and imagined point-to-point arm movements as accurately and as fast as possible, before and after a 90-min sustained cognitive task inducing mental fatigue, and before and after viewing a neutral control task (documentary movie) that did not induce mental fatigue. Target width and center-to-center target distance were varied, resulting in five different indexes of difficulty. Prior to mental fatigue, actual and imagined movement duration increased with the difficulty of the task, as predicted by Fitts' law. Mental fatigue task induced a 4.1±0.7% increase in actual movement duration and a 9.6±1.1% increase in imagined movement duration, independently of the index of difficulty. The trial-by-trial evolution of actual and imagined movement duration remained stable with mental fatigue. The control task did not induce any change in actual and imagined movement duration. The results suggested that movement was slowed in the presence of mental fatigue, maybe due to proactive changes occurring during the preparatory state of the movement, to preserve task success.

Effect of motor imagery in the rehabilitation of burn patients.

Although there is ample evidence that motor imagery (MI) improves motor performance after CNS injury, it is still unknown whether MI may enhance motor recovery after peripheral injury and most especially in the rehabilitation of burn patients. This study aimed to investigate the effects of a 2-week MI training program combined with conventional rehabilitation on the recovery of motor functions in handed burn patients. Fourteen patients admitted to the Medical Burn Center were requested to take part in the study and were randomly assigned to the imagery or the control group. Behavioral data related to the ability to perform each successive step of three manual motor sequences were collected at five intervals during the medical procedure. The results provided evidence that MI may facilitate motor recovery, and the belief in the effectiveness of MI was strong in all patients. MI may substantially contribute to improve the efficacy of conventional rehabilitation programs. Hence, this technique should be considered as a reliable alternative method to help burn patients to recover motor functions.

Modulation of EMG power spectrum frequency during motor imagery.

To provide evidence that motor imagery (MI) is accompanied by improvement of intramuscular conduction velocity (CV), we investigated surface electromyographic (EMG) activity of 3 muscles during the elbow flexion/extension. Thirty right-handed participants were asked to lift or to imagine lifting a weighted dumbbell under 3 types of muscular contractions, i.e. concentric, isometric and eccentric, taken as independent variables. The EMG activity of the agonist (long and short heads of biceps brachii) and the antagonist (long portion of triceps brachii) muscles was recorded and processed to determine the median frequency (MF) of EMG power spectrum as dependant variable. The MF was significantly higher during the MI sessions than during the resting condition while the participants remained strictly motionless. Moreover, the MF during imagined concentric contraction was significantly higher than during the eccentric. Thus, the MF variation was correlated to the type of contraction the muscle produced. During MI, the EMG patterns corresponding to each type of muscle contraction remained comparable to those observed during actual movement. In conclusion, specific motor programming is hypothesized to be performed as a function of muscle contraction type during MI.

Muscular responses during motor imagery as a function of muscle contraction types.

This study was designed to gain more insight into the mechanisms underlying motor imagery (MI). While there is ample evidence that motor performance and MI share common central neural mechanisms, the question whether MI is accompanied by subliminal electromyographic (EMG) activity remained unsolved. Thirty right-handed volunteers were asked to lift or to imagine lifting a weighted dumbbell using different types of muscle contraction, i.e. heavy concentric, light concentric, isometric and eccentric contractions. EMG activity from 9 muscles of the dominant arm (agonist, antagonist, synergist and fixator muscles) was monitored. Autonomic nervous system responses were also recorded on the non-dominant hand, thus attesting mental activity at the peripheral level. A significant increased pattern of EMG activity was recorded in all muscles during MI, when compared to the rest condition, while the goniometric data did not reveal any movement. Although being subliminal, the magnitude of this activation was found to be correlated to the mental effort required to lift a weight mentally, as more EMG activity was recorded during imaginary lifting of heavy than light concentric contractions. When considering the different types of contraction, our results provided evidence of selective changes in EMG activity. Especially, the imagined eccentric condition elicited a significant weaker muscular activity than all other conditions. In addition, the changes in the EMG pattern mirrored those usually observed during physical movement. These findings support the hypotheses of a selective effect of MI at the level of muscular activity and of incomplete inhibition of the motor command during MI.

Coil-to-globule transition of poly(N-isopropylacrylamide) doped with chiral amino acidic comonomers.

By combined light scattering and circular dichroism measurements (CD), we have investigated the coil-to-globule transition of the thermosensitive polymer poly(N-isopropylacrylamide) (pNIPAAm) copolymerized with a 1/10 fraction of valine- or leucine-derived groups randomly positioned along the chains. The comonomers provide the pNIPAAm chains with chirality, electric charge, and increased hydrophobicity. For valine-derived copolymers, the coil-globule transition is basically unmodified with respect to pNIPAAm, whereas doping with leucine-derived groups significantly lowers the transition temperature and makes the transition discontinuous. We find the CD signal of the chiral comonomers to cleanly depend on the local chain density. We interpret this behavior as an effect of the whole chain conformation on the conformations accessible to the chiral groups.

Arylsulfonamides as a new class of cannabinoid CB1 receptor ligands: identification of a lead and initial SAR studies.

High-throughput screening of the UCB sample collection identified the piperidinyl-sulfonyl benzoic ester 1 as a novel agonist for CB(1) receptor with nanomolar affinity. We report here the pharmacological profile of compound 1 as well as preliminary biological activities in pain model. Diverse close analogs of 1 were purchased and the structure-affinity relationships among this novel class are discussed.

Synthesis and structural analysis of the copper(II) complexes of N2-(2-pyridylmethyl)-2-pyridinecarboxamide.

Previous investigations of the potential of metal-organic compounds as inhibitors of human immunodeficiency virus type I protease (HIV-1 PR) showed that the copper(II) complex diaqua [bis(2-pyridylcarbonyl)amido] copper(II) nitrate dihydrate and the complex bis[N2-(2,3,6-trimethoxybenzyl)-4-2-pyridinecarboxamide] copper(II) behaved as inhibitors of HIV-1 PR. In a search for similar readily accessible ligands, we synthesised and studied the structural properties of N2-(2-pyridylmethyl)-2-pyridinecarboxamide (L) copper(II) complexes. Three different crystal structures were obtained. Two were found to contain ligand L simultaneously in a tridentate and bidentate conformation [Cu(L(tri)L(bi))]. The other contained two symmetry-related ligands, coordinated through the pyridine nitrogen and the amide oxygen atoms [Cu(L(bi))(2)]. A search of the Cambridge Structural Database indicated that L(tri) resulting from nitrogen bound amide hydrogen metal substitution is favoured over chelation through the amide oxygen atom. In our case, we calculated that the conformation of L(tri) is 11 kcal/mol more favourable than that of L(bi). ESI-MS experiments showed that the Cu(L(bi))(2) structure could not be observed in solution, while Cu(L(tri)L(bi))-related complexes were indeed present. The lack of protease inhibition of the pyridine carboxamide copper(II) complexes was explained by the fact that the Cu(L(bi)L(tri)) complex could not fit into the HIV-1 active site.

Approaches to the design of effective HIV-1 protease inhibitors.

Recently, western countries have recorded a decrease in the death rate imputed to AIDS. This success has been largely attributed to the presence on the market of chemotherapies that inhibit the infectivity of the predominant causative agent, the HIV-1 virus, by targeting essential viral enzymes. One of these is the protease (HIV-1 PR) whose activity is a prerequisite for viral replication. Two main sites have been identified as potential targets for the inhibition of HIV-1 PR, the active site and the interface, the latter being largely responsible for the stabilization of the enzyme dimeric structure. The compounds that have reached clinical application so far target the active site of HIV-1 PR. These molecules act as transition state analogues and result from modifications of the peptidic scaffold into peptidomimetics. In order to improve their bioavailability, systematic biological screening and de novo design have been used to suggest new non-peptide inhibitors combining both antiviral potency and favorable pharmacokinetic properties. In parallel, compounds targeting other potential sites of inhibition have been tested. Peptides and peptidomimetics based on the terminal sequence of the enzyme, a site which is proposed to be less susceptible to mutations, have been shown to lead to HIV-1 PR inactivation. Cupric ion was described to bind a sequence on the protease surface, which includes cysteine and histidine residues, leading to the inhibition of the enzyme. In the future, these non-active site inhibitors could provide an alternative in anti-HIV drug combination strategies.