Grip force adjustments induced by predictable load perturbations during a manipulative task.

The experiment examined the anticipatory modulation of grip force with respect to load force during a drawer opening task. An impact force was introduced by a mechanical stop that arrested movement of the pulling hand. The results showed a typical grip force profile which consisted of two evolving phases, one to control drawer movement onset, and the other to secure grip force at the expected impact. Initially, grip force increased with the load force that was developed to overcome the inertia of the drawer. After the first peak, a small decline was observed, followed by a proactive grip force increase prior to the time of impact. During this ramp-like increase of grip force, load force remained unchanged. In addition, a reactive response was triggered by the impact. That anticipatory control with respect to an impact force is not innate but, rather, is learned by experience was evidenced by a comparison of adults and children. Whereas adults made the characteristic grip force adjustments to anticipate the impact, children used a probing strategy with irregular build-up of force until impact. Furthermore, adults calibrated the second phase of the grip force profile in the initial trials of the task, indicating that grip force was rapidly updated with information related to the impact force. The present results demonstrate that grip-load force coordination during manipulation is a necessity for dealing with destabilizing load perturbations produced by self-induced movement and impact forces. It is concluded that grip force is adjusted automatically, but in a flexible manner, to secure grip in accordance with the characteristics of the pulling synergy.

Effects of lesions in the mesial frontal cortex on bimanual co-ordination in monkeys.

The hypothesis was tested that the mesial frontal cortex, including the supplementary motor area, is engaged in bimanual co-ordination. Three monkeys, trained in a well-co-ordinated bimanual pull-and-grasp task, were subjected to unilateral or bilateral lesions of the mesial frontal cortex. With unilateral lesions, the deficit consisted in a delay in movement initiation of the contralateral arm. With a bilateral lesion, the deficit was more pronounced with marked bilateral delays in movement onset and slowing in reaching. However, in the three monkeys bimanual co-ordination at the moment of goal achievement remained intact with an excellent temporal co-variation of the two limbs. In the two unilateral cases, an adaptive strategy developed after a few sessions, either by catching up during reaching with the limb contralateral to the lesion (monkey M1) or by delaying movement initiation of the limb ipsilateral to the lesion (monkey M2). This outcome is discussed in terms of Lashley's principle of motor equivalence, i.e. invariant goal achievement with variable means. Bilateral lesions led to a transient and near-total impairment in movement self-initiation when all external cues were absent. It is concluded that in monkeys the mesial frontal cortex does not play a crucial role in bimanual co-ordination but rather in movement initiation, especially when sensory cues are absent.

Temporal structure of a bimanual goal-directed movement sequence in monkeys.

The aim of the present investigation was to assess a bimanual goal-oriented movement sequence with particular emphasis on its temporal structure. The three monkeys (Macaca fascicularis) used in this study chose the left arm as the leading and more postural arm to reach out and pull back a spring-loaded drawer containing a food morsel. The right arm followed the left and picked up the food with a precision grip. Video recordings, trajectory recordings of the two index fingers, drawer displacement and the measurements of discrete events of the left and right hand revealed a considerable trial-by-trial variability in the temporal and spatial domain. The variability of latencies progressively increased from the initiation of the bimanual sequence to the left-hand and right-hand events defining goal achievement. The main result was that, in spite of this variability in each of the two limbs, there was an invariant left-right goal-related synchronization. The timing of the goal-related event pairs covaried and showed high correlation coefficients. Covariation of the two hands resulting in an invariant synchronization was particularly striking when monkeys performed the task without vision, and timing of right and left movement components was delayed with further increase in variability. The results indicate that, in the present bimanual skill, kinaesthetic signals may be sufficient to coordinate the two limbs in a goal-oriented unitary action in accord with a memorized plan.

The action of new potent GABAB receptor antagonists in the hemisected spinal cord preparation of the rat.

CGP 52432 (3-N-(3,4-dichlorobenzyl)aminopropyl-P-diethoxymethylphosphinic acid), CGP 54062 (3-N[1-(R,S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P-benzy l- phosphinic acid), CGP 54626 (3-N[[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)- hydroxypropyl-P-cyclohexylmethylphosphinic acid) and CGP 55845 (3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)- hydroxypropyl-P-benzyl-phosphinic acid) are novel selective GABAB receptor antagonist. The apparent Kd values for the complex formed between the GABAB receptor and these compounds were determined using the monosynaptic reflex in the hemisected rat spinal cord preparation in vitro. CGP 55845 was found to be the most potent GABAB receptor antagonist tested (apparent Kd = 30 nM). On the same preparation 0.3 microM CGP 55845 was equipotent with 100 microM of CGP 35348 (P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid) for reversal of the depressant action of (R)-(-)-baclofen.

Modulation of the NMDA receptor by D-serine in the cortex and the spinal cord, in vitro.

We present a comparative study of the modulation of the N-methyl-D-aspartate (NMDA) receptor at the strychnine-insensitive glycine site in the spinal cord and in the cortex. The excitatory effect of NMDA was potentiated by D-serine (a glycine mimetic) in the hemisected rat spinal cord. The non-competitive NMDA antagonists 7-chlorokynurenic acid (7-Cl KYNA; 10 microM) and 3-amino-1-hydroxypyrrolid-2-one (HA-966; 100 or 200 microM) antagonized the effect of NMDA in the spinal cord and cortical wedge preparation. The antagonism was reversed by the addition of D-serine. This effect was strychnine-insensitive and hence not related to the inhibitory glycine receptor known to be present in the spinal cord. Our results suggest strongly that glycine positively modulates the NMDA system not only at a supraspinal level but also at the spinal level. As the positive modulation of NMDA responses by D-serine was also seen in the presence of tetrodotoxin, we conclude that the NMDA/glycine complex is (also) located on motoneurones in addition to the known glycine-mediated inhibitory system.