Vision without proprioception modulates cortico-spinal excitability during hand motor imagery.

Several studies have shown a cortico-spinal facilitation during motor imagery. This facilitation effect is weaker when the actual hand posture is incompatible with the imagined movement. To determine whether the source of this interference effect arises from online proprioceptive information, we examined transcranial magnetic stimulation (TMS)-induced motor-evoked potentials during motor imagery in the deafferented subject G.L. The patient and 7 control subjects were asked to close their eyes and imagine joining the tips of the thumb and the little finger while maintaining a hand posture compatible or incompatible with the imagined movement. Contrary to control subjects' performance, G.L.'s results show that the facilitation observed during motor imagery was independent of the hand posture. To examine how vision of the hand interacts with the imagery process, G.L. and control subjects performed the same task with the eyes open. Like control subjects, when G.L. looked at her hand, a greater facilitation was observed when her hand posture was compatible with the imagined movement than when it was incompatible. These results suggest that in the absence of proprioception, vision may facilitate or inhibit motor representations and support the idea that limb position in the brain is organized around multisensory representations.

The role of proprioception in action recognition.

This study aimed at evaluating the role of proprioception in the process of matching the final position of one's limbs with an intentional movement. Two experiments were realised with the same paradigm of conscious recognition of one's own limb position from a distorted position. In the first experiment, 22 healthy subjects performed the task in an active and in a passive condition. In the latter condition, proprioception was the only available information since the central signals related to the motor command were likely to be absent. The second experiment was realised with a deafferented patient who suffers from a complete haptic deafferentation, including loss of proprioception. The results first argue in favour of a dominant role of proprioception in action recognition, but they also stress the possible role of central signals. The process of matching the final position of one's limbs with an intended movement and thus of action recognition would be achieved through a comparison process between the predicted sensory consequences of the action, which are stored in its internal model, and the actual sensory consequences of that action.

Role of the feedforward command and reafferent information in the coordination of a passing prehension task.

The performances of a deafferented patient and five control subjects have been studied during a self-driven passing task in which one hand has to grasp an object transported by the other hand and in a unimanual reach-to-grasp task. The kinematics of the reach and grasp components and the scaling of the grip aperture recorded for the self-driven passing task were very similar in controls and the deafferented subject (GL). In contrast, for the unimanual task when vision was absent, GL's coordination between reaching and grasping was delayed in space and time compared with the control subjects. In addition, frequent reopening of the grip was observed in GL during the final closure phase of the unimanual prehension task. These results support the notion that afferent proprioceptive information resulting from the reaching movement - which seemed to be used to coordinate reaching and grasping commands in the unimanual task - is no longer necessary in the self-induced passing task. Finally, for the externally driven passing task, when the object was passively transported by the experimenter, the coordination was consistently modified in all subjects; grip aperture onset was delayed, thus asserting a specific contribution of the central command or feedforward mechanisms into the anticipation of the grasp onset observed in the self-driven passing task. The origin and nature of the information necessary for building up the feedforward mechanisms remains to be elucidated.

Gait of a deafferented subject without large myelinated sensory fibers below the neck.

We evaluated the gait pattern of a deafferented subject who suffered a permanent loss of large sensory myelinated fibers below the neck following an acute episode of purely sensory neuropathy 21 years ago. The subject has developed several strategies to achieve a secure gait, namely: (1) a reduction of the degrees of freedom by freezing the knee articulations during the stance phase, (2) a preservation of body balance by enlarging his base of support, and (3) visual monitoring of his step by stabilizing the head-trunk linkage together with a characteristic forward tilt. As a result, the gait of the deafferented subject lacks the fluidity of normal gait. Compared with normal subjects, the gait pattern of the deafferented subjects is characterized by a shorter cycle length, a longer cycle duration, a slower speed, and a lower cadence. Using a dual-task paradigm, the attentional demands for walking were particularly important (as indexed by longer probe reaction times) during the double-support phase, suggesting that the deafferented subject uses the double-support phase as a transitory stable phase to update cognitively the postural features necessary for generating his next step.

Control of single-joint movements in deafferented patients: evidence for amplitude coding rather than position control.

Two deafferented patients and several control subjects participated in a series of experiments to investigate how accurate single-joint movements are programmed, spatially calibrated, and updated in the absence of proprioceptive information. The deafferented patients suffered from a permanent and severe loss of large sensory myelinated fibers below the neck. Subjects performed, with and without vision, sequences of forearm supinations and pronations with two temporal delays between each movement (0 s and 8 s). Overall, the lack of proprioception did not yield any significant decrease in movement accuracy when vision was available. Without vision, the absence of proprioceptive afferents yielded (1) significantly larger spatial errors, (2) amplitude errors similar to those of control subjects, and (3) a significant drift when an 8-s delay was introduced between two successive movements. Subjects also performed, without vision, a 20 degrees supination followed by a 20 degrees pronation that brought back the wrist to the starting position. On some trials, the supination was blocked unexpectedly by way of a magnetic brake. When the supination was blocked, subjects were already on the second target and no pronation was required when the brake was released. The deafferented patients, unaware of the procedure, always produced a 20 degrees pronation. These data confirm that deafferented patients were not coding a final position. It rather suggests that they coded an amplitude and translated the spatial distance between the two targets in a corresponding force pulse. Overall, the results highlight the powerful and key role of proprioceptive afferents for calibrating the spatial motor frame of reference.

Fast and slow feedback loops for the visual correction of spatial errors in a pointing task: a reappraisal.

Experimental evidence supporting the idea that central and peripheral vision play a distinctive role in the on-line visual guidance of reaching movements is reappraised. The central retina, highly sensitive for the discrimination of relative position cues, subserves the error-detecting mechanisms that encode the discrete rate of change of location of the moving hand relative to the stationary target, feeding the slow corrective feedback loops that allow the accurate homing in of the hand on the target. The peripheral retina, mainly sensitive for the detection of continuous motion cues, is swept by the image of the hand moving towards the fovea, which is itself strongly anchored to the target during the whole course of the movement, thus providing a directional error signal used for fast correction of the movement trajectory. This interpretation fits a two-system model of motion perception derived from psychophysical data. It also fits anatomical and physiological data concerning the central distribution of static and kinetic cues through two separate visual channels. However, the way in which reafferent visual information involved in both feedback loops is further conveyed to the control system of arm-hand movement remains largely unknown.

Naturally occurring somatostatin and vasoactive intestinal peptide inhibitors. Isolation of alkaloids from two marine sponges.

The vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor, SRIF) are important neurotransmitters in a number of basic physiological events. Their disturbances have been reported in many diseases such as cystic fibrosis, impotent man (VIP), Alzheimer's disease, and some tumours (SRIF). Xestospongine B (1), sceptrine (2), and ageliferine (3), three alkaloids isolated from Xestospongia sp. and Agelas novaecaledoniae are reported as somatostatin and VIP inhibitors. The natural products 1, 2 and 3 exhibited a high affinity for somatostatin (IC50 = 12 microM, 0.27 microM, and 2.2 microM, respectively), 2 and 3 showed an affinity for VIP (19.8 microM and 19.2 microM, respectively). Due to the interaction between non-peptidic compounds and somatostatin/VIP receptors, these three alkaloids could be promising agents in the research on natural non-peptidic compounds for therapeutical interventions.

Perception of passive whole-body rotations in the absence of neck and body proprioception.

1. This study investigated whether accurate perception of body rotation after passive horizontal whole-body rotations in the dark requires the integration of both vestibular and neck-body proprioceptive signals. 2. In the first experiment, the gain of the vestibuloocular reflex (VOR) of normal subjects ("controls") and of a patient without proprioception of the neck and body muscles was assessed by the use of pulse and sinusoidal stimulation. In the second experiment, the subjects reported verbally the magnitude of the body rotations. Finally, in the third experiment, they shifted gaze to the position fixated before the rotation ("vestibular memory-contingent saccades" paradigm). 3. The VOR gain of the patient was similar to that of controls, although the body rotations of the patient were largely overestimated, regardless of whether the patient reported the perceived magnitude verbally or through a gaze shift toward the position gazed at before the rotation. 4. These results suggest that neck muscle proprioception contributes to the vestibular signal calibration at the perceptual level necessary for determining body orientation accurately after rotations in the dark.

Weight judgment. The discrimination capacity of a deafferented subject.

A weight discrimination study was undertaken to test (i) the capacity of controls and a deafferented subject (deprived of large sensory myelinated fibres from nose down), to discriminate weights with and without vision; (ii) the capacities of observers to discriminate weights while watching the deafferented and control subjects' lifting movements; (iii) the contribution of supplementary sources of sensory information (e.g. vestibular afferents) to the deafferented subject's discrimination capacity. With vision, G.L.'s liminal discrimination of weights was similar to that of the controls. In contrast, precluding vision impaired massively, but not completely, G.L.'s discrimination capacity, so emphasizing the importance of visual kinaesthetic cues in G.L. and incidently the importance of large myelinated sensory function in weight discrimination in controls. Kinematics recordings of G.L.'s lifting movements with vision revealed a significant correlation between weight and peak velocity of the lifting movement. This reflects a specific strategy used by G.L. to generate movements, allowing her to judge the weight of a lifted object visually. Peak velocity rather than amplitude of movement appears to be the main cue for G.L. since there was a lack of correlation between amplitude and weight lifted. For controls, none of the correlations (weight versus amplitude or weight versus velocity) was significant, whether vision was available or not. When watching G.L.'s lifting performance, external observers were able to use similar cues to establish their judgments, but they were far less accurate in doing so when watching control subjects. This suggests that controls were using a strategy different from G.L.'s.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of proprioception for calibrating and updating the motor space.

The absence of muscular proprioception, whether at a segmental or at a central level, impairs performance in several ways. The contribution of proprioception to movement control and learning is not easily dissociated from that of other sources of sensory information (e.g., vision). Therefore, the rare clinical cases of extensive neuropathy, depriving the brain massively and permanently of its presumed main sources of dynamogenic information from skin and muscles, are of very special interest. Two such patients and controls were tested in experiments investigating (i) force production, (ii) amplitude coding, (iii) spatial reference frames in pointing, and (iv) prismatic adaptation. Overall, our results highlight the key role of proprioceptive afferents for calibrating the spatial motor frame of reference, and the powerful substitutive properties of the central nervous system.

Is proprioception important for the timing of motor activities?

This study tested whether a deafferented patient demonstrates impaired timing ability compared with four control subjects. By comparing normal subjects with the deafferented patient, some insight was expected on the importance of proprioception in timing of motor behavior. The protocol was set to enhance the strategy of the subjects in using feedbacks. Subjects had to synchronize finger taps with a sound produced at regular intervals. Once synchronized, the bips were muted and the subjects had to continue the tapping at the same pace. Interresponse interval (IRI) variability was measured under two feedback conditions: with and without vision and auditory feedback. The Wing and Kristofferson model (A.M. Wing and A.B. Kristofferson. Percept. Psychophys. 13(3): 455-460, 1973) was used to segment IRI variance into separate components: a central clock and a peripheral motor delay. When the deafferented patient saw and heard the outcome of her tapping movements, there was a greater variability in successive intervals between taps than when vison and hearing were blocked. We interpret this variability as indicating that the subject used auditory and visual feedback to maintain a correct overall rhythm. The patient may easily substitute visual and (or) auditory feedback for her defective proprioception for movement timing. However, this substitution proved to be inefficient in the limited training period provided in this experiment. The results suggest that the proprioceptive contribution to the time-keeping mechanism presumably depends on the presence of an efference copy signal.

Production of short timing responses: a comparative study with a deafferented patient.

How far can proprioception contribute to time keeping? To answer this question, a deafferented patient and neurologically normal subjects produced 1- or 5-sec durations in a sustained (continuous finger press) or discrete (two successive finger taps) manner, with and without Knowledge of Results. The findings were that: (1) proprioceptive afferents contribute to timing regulation in motor production of short durations; (2) this role can be rapidly compensated by Knowledge of Results; (3) the proprioceptive contribution is more important for sustained than for discrete performances; (4) stable performances are produced even when KR is withdrawn, suggesting familiarization with KR leads to the establishment of a mnemonic trace.

The role of proprioceptive information for the production of isometric forces and for handwriting tasks.

A patient showing a total loss of all the large sensory myelinated fibers but intact peripheral motor system produced simple isometric force pulses and more complex tasks like handwriting and drawing. Overall, the patient was able to perform the isometric force task with an accuracy that approached that of normal subjects. The writing tasks, however, proved to be more challenging. In absence of vision, the different forms and cursive trajectories forming letters (morphocinetic components) were preserved but their localization within the constraints of the graphic space (topocinetic components) were severely impaired. These results demonstrate that, in absence of visual information, proprioceptive information is necessary to calibrate the hand in space.

Reference systems for coding spatial information in normal subjects and a deafferented patient.

To produce accurate goal-directed arm movements, subjects must determine the precise location of target object. Position of extracorporeal objects can be determined using: (a) an egocentric frame of reference, in which the target is localized in relation to the position of the body; and/or (b) an allocentric system, in which target position is determined in relation to stable visual landmarks surrounding the target (Bridgeman 1989; Paillard 1991). The present experiment was based on the premise that (a) the presence of a structured visual environment enables the use of an allocentric frame of reference, and (b) the sole presence of a visual target within a homogeneous background forces the registration of the target location by an egocentric system. Normal subjects and a deafferented patient (i.e., with an impaired egocentric system) pointed to visual targets presented in both visual environments to evaluate the efficiency of the two reference systems. For normals, the visual environment conditions did not affect pointing accuracy. However, kinematic parameters were affected by the presence or absence of a structured visual surrounding. For the deafferented patient, the presence of a structured visual environment permitted a decrease in spatial errors when compared with the unstructured surrounding condition (for movements with or without visual feedback of the trajectory). Overall, results support the existence of an egocentric and an allocentric reference system capable of organizing extracorporeal space during arm movements directed toward visual targets.

99Tcm-HMPAO-labelled leucocyte scintigraphy in suspected chronic osteomyelitis related to an orthopaedic device: clinical usefulness.

Thirty-five patients with suspected chronic osteomyelitis related to an orthopaedic device had 50 99Tcm-HMPAO-labelled leucocyte scans (LS). The scan appearances were compared with the bacteriological or clinical results and gave a sensitivity and specificity of HMPAO-LS of 83 and 100%, respectively. Bacteriological examination is often inaccurate in the diagnosis of osteomyelitis and therefore we assessed the clinical utility of HMPAO-LS. When the clinical, biological and radiological data were clearly suggestive of osteomyelitis (16/50) LS was unhelpful or even misleading when falsely negative (3/16). When the clinical, biological and radiological data were poorly suggestive of osteomyelitis (20/50) or conflicting (14/50) LS was misleading in only one patient (false negative). It is concluded that HMPAO-LS should only be performed to assist in the diagnosis of chronic osteomyelitis when there is no preexisting strong suspicion based on clinical, biological and radiological signs.

Mirror drawing in a deafferented patient and normal subjects: visuoproprioceptive conflict.

Results on a mirrow drawing task showed that a deafferented patient had no problem completing the pattern, whereas normal subjects needed more than four trials to attain a similar performance. The results suggest the presence of integrated visual and proprioceptive maps. The inversion of visual coordinates requires the need for a recalibration. Without proprioception, the task is more like a simple visual tracking task.

Role of afferent information in the timing of motor commands: a comparative study with a deafferented patient.

The accuracy of the motor system in synchronizing simultaneous movements initiations was tested in two conditions: (1) when the motor commands were triggered by an external signal (reactive condition), and (2) when subjects self-paced their movement onsets (self-paced condition). The task consisted of initiating simultaneously ipsilateral finger extension and heel raising. Eight normal subjects and a deafferented patient were tested. In the reactive condition, both normal subjects and the deafferented patient exhibited a precession of finger initiation over heel raising. This delay corresponds to the difference observed in the reaction time of the two limbs when measured independently. It reflects the difference in conduction times of the efferent pathways, as if the two motor commands were released simultaneously through a common triggering signal in the motor cortex. In contrast, in the self-paced condition normal subjects showed precession of heel over finger onsets, suggesting that synchrony is based upon the evaluation of afferent information. Unlike normal subjects, the patient showed no heel precession in the self-paced condition. These findings suggest that reactive and self-paced responses are produced through two different control modes and that afferent information contributes to the timing of motor commands in the self-paced mode.

Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma.

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.

[Motor neglect: issues and prospects]. / A propos de la négligence motrice: issues et perspectives.

Although the motor and sensory components of the neglect syndrome appear as dependent on a unitary attentional process, the clinical observation of pure motor neglect raises the possibility of segregation between attentional and intentional neural mechanisms. Neuroanatomical evidence suggests a separate role for the anterior and posterior cingulum. The anterior cingulum mainly projects to the supplementary motor area, the superior premotor area and the prefrontal granular cortex whereas the posterior cingulum mainly controls the inferior parietal lobule. The role of the intralaminar thalamic nuclei, together with the frontostriatal loops is considered. Behavioral neurology should strengthen its analytical approach in order to dissociate, by appropriate testing, the separate operations which contribute to relate perception and action. Several new hypotheses are presented.

Evidence that clomethiazole interacts with the macromolecular GABA A-receptor complex in the central nervous system and in the anterior pituitary gland.

Clomethiazole (CLOM) is known to be an anticonvulsant drug and has been also reported to decrease serum prolactin (PRL) in humans. Both effects may be mediated by an enhancement of gabaergic transmission. In order to determine if (CLOM) interacts with GABA metabolism and/or at the GABA receptor level, we studied its effect on PRL release and on the binding of various compounds that interact with the GABAA-benzodiazepine-receptor complex. Intraperitoneal (IP) administration of CLOM to rats significantly decreased PRL levels, and this effect was antagonized by IP administration of bicuculline, an antagonist of the GABAA receptor. In vitro, the inhibitory effect of muscimol on PRL release from rat hemiadenohypophysis was potentiated in a dose-dependent manner by preincubation with CLOM. This effect was antagonized by picrotoxin (10(-6) M). On the other hand, CLOM had no effect on GABA metabolism and did not compete with GABAA, GABAB or benzodiazepine binding sites in cortical membranes. CLOM competed, however, with the picrotoxin binding site labelled with [35S]-butylbicyclophosphorothionate (TBPS), at an IC50 value of 1.2 x 10(-4) M, which is in the same range as some barbiturates. These results concerning PRL release and binding experiments with cortical membranes suggest that CLOM interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex.