Sensorimotor mapping of the human cerebellum during pineal region surgery.

BACKGROUND: The cerebellum is a fundamental structure of the central nervous system. However, in humans, its anatomo-functional organization and the processes through which this organization adapts in response to injuries remain widely unknown. METHODS: Motor and somatosensory evoked potentials were used to map functional representations in the posterior cerebellum of patients with extra- and intracellebellar injuries. Extracerebellar patients had injuries outside the cerebellum (e.g. pineal region, quadrigeminal plate) while intracerebellar patients had injuries within the cerebellum. Data were collected in 20 extracerebellar patients for motor representations. Only preliminary data were gathered for somatosensory representations and intracerebellar patients. RESULTS: In extracerebellar patients, electrical stimulation induced muscle contractions in the ipsilateral hemibody. These representations were somatotopically organized with large overlaps between the face and upper limb in the superior posterior cerebellum and the upper and lower limb in the inferior posterior cerebellum. Neck muscles were represented in the oculomotor vermis. In intracerebellar patients, preliminary data seem to indicate that motor plasticity is achieved by recruiting the contralesional (healthy) cerebellar hemisphere. CONCLUSIONS: Although still ongoing, this project could eventually lead to an improvement of the surgical treatment of patients with lesions of the posterior fossa, by improving our knowledge of cerebellar organization and the process of post-lesional plasticity.

[Functional magnetic resonance imaging. What are the benefits expected in hand surgery?]. / IRM fonctionnelle. Quels apports en chirurgie de la main ?

Functional MRI (fMRI) allowed considerable advances upon understanding of cerebral functioning. Cortical plasticity, which allows the voluntary command of a restored function by a transferred muscle remains to be investigated in its intimacy. The authors present here the round table held at the 48th annual meeting of the French Society for Surgery of the Hand on December 22nd, 2012. It tries to review the analysis of the phenomenon observed during multiple tendinous transfers for restoration of proximal radial nerve palsy. Were successively approached: 1) Methods of acquisition and analysis of the signals (C. D-M.); 2) Movement reorganization (O.M.); 3) Motor plasticity after hand allograft (A. S.); 4) The potential interest of the fMRI in hand rehabilitation (F. D.); 5) The analysis of cerebral plasticity in general (H. B.). A rather philosophical conclusion opens other fields to f MRI (A.M.).

Role of the parietal cortex in predicting incoming actions.

Animal and human studies have shown that the parietal and the ventral premotor cortices constitute the neural substrate of the so-called mirror system. The word "mirror" originally referred to the discovery of neurons in non-human primates whose visual response echoes their motor response. This account proposes that action understanding and imitation depend on a mechanism which activates directly our own motor system as we observe the actions of other agents (Rizzolatti and Sinigaglia, 2010). Single unit recording experiments have also demonstrated that parietal neurons have predictive activity and discharge well ahead of a planned movement. Interestingly, patients with parietal damage can show impairments in their ability to imitate or understand an observed action, but they have also difficulties in monitoring early phases of their own movement planning, be it simple reaching movements or more complex object-directed actions. The fact that both deficits may co-occur after a parietal lesion raises the question whether this reflects the impairment of a common mechanism. To address this question we examined EEG activity in patients with selective lesions in the inferior parietal lobe (N=6) who were requested to watch passively a video showing an actor grasping a colored object. The object's color cued the subject that the actor was about to move. We recorded the Readiness Potential (RP), a marker of motor preparation which also arises when preparing to observe an action (Kilner et al., 2004). Parietal patients' performance was compared to that of neurologically normal subjects (n=9) and patients with a ventral premotor cortex lesion (N=4). We show that neurologically normal subjects and premotor patients exhibit a significant RP prior to the observed action, whereas no such RP is observed in parietal patients. Our results indicate that parietal cortex injury alters the ability to monitor the early planning phases not only of one's own actions but those of other agents as well. We speculate that parietal activity during action observation does not only or essentially reflect a mirroring process, as recently proposed by mirror neurons' account, but involve instead an anticipatory process which arises through prior learning and predictive mechanisms.

The role of the right parietal lobe in anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa (AN) overestimate their size despite being severely underweight. Whether this misperception echoes an underlying emotional disturbance or also reflects a genuine body-representation deficit is debatable. Current measures inquire directly about subjective perception of body image, thus distinguishing poorly between top-down effects of emotions/attitudes towards the body and disturbances due to proprioceptive disorders/distorted body schema. Disorders of body representation also emerge following damage to the right parietal lobe. The possibility that parietal dysfunction might contribute to AN is suspected, based on the demonstrated association of spatial impairments, comparable to those found after parietal lesion, with this syndrome. METHOD: We used a behavioral task to compare body knowledge in severe anorexics (n=8), healthy volunteers (n=11) and stroke patients with focal damage to the left/right parietal lobe (n=4). We applied a psychophysical procedure based on the perception, in the dark, of an approaching visual stimulus that was turned off before reaching the observer. Participants had to predict whether the stimulus would have hit/missed their body, had it continued its linear motion. RESULTS: Healthy volunteers and left parietal patients estimated body boundaries very close to the real ones. Conversely, anorexics and right parietal patients underestimated eccentricity of their left body boundary. CONCLUSIONS: These findings are in line with the role the parietal cortex plays in developing and maintaining body representation, and support the possibility for a neuropsychological component in the pathogenesis of anorexia, offering alternative approaches to treatment of the disorder.

Selective activation of human finger muscles after stroke or amputation.

Individuated finger movements of the human hand require selective activation of particular sets of muscles. Such selective activation is controlled primarily by the motor cortex via the corticospinal tract. Is this selectivity therefore lost when lesions damage the corticospinal tract? Or when the motor cortex reorganizes after amputation? We studied finger movements in normal human subjects and in patients who had recovered substantially from pure motor hemiparesis caused by lacunar strokes, which damage the corticospinal tract without affecting other pathways. Even after substantial recovery from these strokes, individuation of finger movements remained reduced-both for flexion/extension and for adduction/ abduction motion of the fingers. Stroke subjects regained the ability to move the instructed digit through a normal range, but unintentional motion of other digits was increased. This increase did not result from a change in the passive biomechanical coupling of the fingers. Rather, voluntary contractions of muscles that move the intended digit were accompanied by inappropriate contractions in muscles acting on additional digits. These observations suggest that the normal corticospinal system produces individuated finger movements not only by selectively activating certain muscles, but also by suppressing activation of other muscles during voluntary effort to move a given digit. In a separate experiment, reversible amputation of the hand was produced in normal subjects by ischemic nerve block at the wrist. Motor output to the intrinsic muscles and sensory input both become blocked under these conditions, effectively amputating the hand from the nervous system. But the long extrinsic muscles that flex and extend the digits remain normally innervated, and thus flexion forces still can be generated at the fingertips. During reversible amputation of the hand produced by ischemic nerve block, the ability of subjects to activate subdivisions of extrinsic muscles and to exert flexion force at individual fingertips continued to show essentially normal selectivity. Voluntary activation of the remaining muscles thus continues to be selective after amputation, in spite of both the loss of sensory input from the amputated hand, and reorganization within the primary motor cortex. During cortical reorganization after amputation, then, voluntary patterns of motor output intended for finger muscles may not be lost. We therefore examined activity in the stump muscles of above-elbow amputees, who have no remaining hand muscles. Different movements of the phantom hand were accompanied by different patterns of EMG in remaining proximal muscles, distinct from the EMG patterns associated with movement of the phantom elbow. We infer that voluntary motor output patterns that normally control finger movements after amputation may become diverted to remaining proximal muscles.

Integrated approach to TYLCD management in Sardinia (Italy).

In Sardinia (Italy) Tomato yellow leaf curl disease (TYLCD) re-emerged in 2003, after a period of decline, producing severe yield losses in protected tomato crops. This epidemic outbreak highlighted the inadequacy of the approach to TYLCD management based chiefly on the chemical control of its vector, the whitefly Bemisia tabaci, and the use of 40-mesh nets for greenhouse screening. To evaluate the reliability of alternative practices for implementation within IP&DM programmes, in 2007 and 2008 we carried out two field experiments on greenhouse tomato crops planted in summer. In both trials we tested the use of UV-reflective mulches (UVRM) or floating row covers (NWRC), against an uncovered control on clear mulch. Furthermore, we assessed the effectiveness of acibenzolar-S-methyl, a SAR elicitor, as subplot factor in a split plot design. In 2007 because of the low incidence of the disease it was not possible to assess differences among the treatments. However a significant increase in plant growth, and production was observed in UVRM plots. By contrast, in 2008 the study crop was seriously affected by TYLCD. In the plots not treated with acibenzolar-S-methyl, the disease progression was initially slowed down in NWRC and, to a lesser extent, in UVRM plots compared to control plots but, during the second month of the cropping period, the differences among treatments became statistically not significant. In the plots treated with acibenzolar-S-methyl the dynamics of TYLCD infection during the first five weeks exhibited the same trend as in the untreated plots. Thereafter, the combination of UVRM and, to a lesser extent, of NWRC with the SAR elicitor resulted in a reduction of disease incidence with respect to the control. In conclusion, all the control measures tested in the present work showed the potential for TYLCD management in greenhouse tomatoes. However, the most promising results were achieved using UV-reflective mulch and non-woven row cover in combination with acibenzolar-S-methyl. In view of its positive impact on plant growth and yield in summer planted tomato crops, as well as on TYLCD infection, the use of UV-reflective mulch warrants further investigation.

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.

[Hand allografts: experience from Lyon team]. / Allogreffe de mains: expérience lyonnaise.

Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level of amputation was at the wrist or at the mid-forearm. Delay since hand loss ranged from 2.5 to 9 years. The surgical protocol was elaborated and planned case by case. All recipients received the same immunosuppressive treatment. Episodes of acute rejection were observed in the first 3 months after transplantation, which were easily managed after a few days increasing oral prednisone doses and applying topical immunosuppressants. Currently the patients receive the doses of immunosuppressants comparable to those in kidney-grafted patients. We have not registered any severe complication of immunosuppressive treatment up till now (7 years follow-up for the earliest graft). We performed analytical and functional clinical, as well as questionnaire evaluation of patients. The first case (unilateral graft) resulted in graft failure at 2 years due to non-compliance of the patient. The three bilateral graftees demonstrate a favorable evolution despite some immunological (hyperglycemia, serum sickness) and surgical (thrombosis, osteomyelitis, skin loss) complications, which could be managed. The middle and long-term follow-up evaluation revealed good to excellent sensorimotor recovery of 4 hands in both male recipients (4 and 7 years) with satisfactory social adaptation, higher or equal to those expected after post-traumatic replantations at the equivalent level and higher to those obtained with currently available myoelectric prosthesis. The last patient, a young female who has been grafted in February 2007, receives ongoing reeducation course and shows normal progress of functional restoration of both hands. The encouraging results of this clinical experimentation make us currently consider hand allografting as reasonable and useful both for the patients and for evolution of research in composite tissues allotransplantation (CTA). Further long-term careful research and worldwide monitoring of all patients with hand allografts is required to, on the one part, state on the authorization of this surgery, and, on the other part, to better elucidate the mechanisms of successful CTA.

[The nature of the sense of effort and its neural substrate]. / Nature et substratum neurologique du sens de l'effort.

INTRODUCTION: What are the nature and the neural substrate of voluntary force perception? STATE OF ART: Experimental findings demonstrate that efferent signals related to motor command play a dominant role in perceiving voluntary muscular force. This suggests that voluntary force perception is provided through a sense of effort and not through a sense of intramuscular tension. Nevertheless, experimental data show that the contribution of sensory input to effort awareness must not be dismissed. Sensory signals are not involved in generating a signal of effort but rather in calibrating and modulating its magnitude. Neuroimaging and neuropsychological studies revealed that many cortical structures are activated during tasks of voluntary muscular force perception. PERSPECTIVES AND CONCLUSION: In such tasks, the basal ganglia might support the coherence of cortical activity.

Bilateral hand transplantation: six years after the first case.

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

The influence of hand posture on corticospinal excitability during motor imagery: a transcranial magnetic stimulation study.

In order to study the interaction between proprioceptive information and motor imagery, we herein investigate how compatible and incompatible postural signals influence corticospinal excitability during the mental simulation of hand movements. Subjects were asked to imagine themselves joining the tips of the thumb and the little finger while they maintained one of the two following hand postures: posture A (PA, compatible), little finger, index and thumb extended, the remaining fingers flexed; or posture B (PB, incompatible), index and thumb extended, other fingers flexed. All subjects rated the imagined finger opposition movements as easier to perform when the hand was kept in PA than in PB (P < 0.01) and the correlation between the duration of motor imagery and movement execution was also higher for PA than PB (P < 0.01). For each posture, motor evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right opponens pollicis muscle during both motor imagery (MI) and rest (R) conditions. MEP area varied according to the hand posture: PA induced a higher increase in corticospinal excitability, when compared with PB. These results indicate that the actual limb posture affects the process of motor imagery. The source of this postural modulation effect is discussed.

Illusory movements of the paralyzed limb restore motor cortex activity.

In humans, limb amputation or brachial plexus avulsion (BPA) often results in phantom pain sensation. Actively observing movements made by a substitute of the injured limb can reduce phantom pain, Proc. R. Soc. London B Biol. Sci. 263, 377-386). The neural basis of phantom limb sensation and its amelioration remains unclear. Here, we studied the effects of visuomotor training on motor cortex (M1) activity in three patients with BPA. Functional magnetic resonance imaging scans were obtained before and after an 8-week training program during which patients learned to match voluntary "movements" of the phantom limb with prerecorded movements of a virtual hand. Before training, phantom limb movements activated the contralateral premotor cortex. After training, two subjects showed increased activity in the contralateral primary motor area. This change was paralleled by a significant reduction in phantom pain. The third subject showed no increase in motor cortex activity and no improvement in phantom pain. We suggest that successful visuomotor training restores a coherent body image in the M1 region and, as a result, directly affects the experience of phantom pain sensation. Artificial visual feedback on the movements of the phantom limb may thus "fool" the brain and reestablish the original hand/arm cortical representation.

Renal size and function in patients with neuropathic bladder due to myelomeningocele: the role of growth hormone.

PURPOSE: Patients with spina bifida have smaller kidneys than healthy individuals. We evaluated the correlation between small size and decreased renal function, and the possible role of growth hormone deficiency. MATERIALS AND METHODS: A total of 54 patients (mean age 11.5 years, median 11, standard deviation +/- 4.52) were healthy except for neuropathic bladder due to spina bifida. Renal function was evaluated with mercaptoacetyltriglycine renal scintigraphy and creatinine clearance. Renal anatomy was evaluated with renal ultrasound and voiding cystourethrography. Serum insulin-like growth factor-1 (IGF-1) levels were measured in all patients with immunoradiometric assay. Renal measurements in our patients were compared using the Sutherland nomogram. RESULTS: A total of 22 patients (41%) had smaller kidneys than normal subjects and 31 appeared to have creatinine clearance values lower than 120 ml per minute per 1.73 m2. The statistical comparison between kidney size and creatinine clearance was significant (p <0.05, r = 0.381). Scintigraphic data showed total effective renal plasma flow less than 568 ml per minute per 1.73 m2 body surface area (normal mean value for age). Comparison between effective renal plasma flow and creatinine clearance was significant (p <0.05, r = 0.31). Serum levels of IGF-1 were normal for age in all patients (mean 332.06 ng/ml, median 303.4, range 39.4 to 732.3). CONCLUSIONS: The kidneys are smaller in patients with spina bifida than in healthy subjects when compared using the Sutherland nomogram. There is a significant correlation between smaller renal length and decreased renal function in all patients, even in those who are healthy except for neurogenic bladder secondary to spina bifida. IGF-1 levels were normal for age, and, therefore, these patients had no growth hormone deficiency. These findings call into question the hypothesis that growth hormone deficiency contributes to smaller kidney size. Other hypotheses can be suggested, such as a defect of embryological growth secondary to malformation, or the result of a defect in homocysteine-methionine metabolism.

Motor and visual imagery as two complementary but neurally dissociable mental processes.

Recent studies indicate that covert mental activities, such as simulating a motor action and imagining the shape of an object, involve shared neural representations with actual motor performance and with visual perception, respectively. Here we investigate the performance, by normal individual and subjects with a selective impairment in either motor or visual imagery, of an imagery task involving a mental rotation. The task involved imagining a hand in a particular orientation in space and making a subsequent laterality judgement. A simple change in the phrasing of the imagery instructions (first-person or third-person imagery) and in actual hand posture (holding the hands on the lap or in the back) had a strong impact on response time (RT) in normal subjects, and on response accuracy in brain-damaged subjects. The pattern of results indicates that the activation of covert motor and visual processes during mental imagery depends on both top-down and bottom-up factors, and highlights the distinct but complementary contribution of covert motor and visual processes during mental rotation.

Action planning in a virtual context after prefrontal cortex damage.

Patients with frontal lobe lesions are known to encounter severe problems in the organisation of their behaviour in everyday life. Script generation tasks assess the subject's conceptual ability to formulate and evaluate a coherent and structured plan of action. In the present study, we investigated to what extent neuropsychological deficits observed at the conceptual level of action knowledge lead to impairments in action execution. We examined seven patients with prefrontal cortex damage and sixteen normal subjects. Subjects were first asked to verbally formulate a plan of action and then to use this knowledge for 'executing' the actions in a virtual 3-dimensional interactive apartment presented on a computer screen. The results indicated that the presence of the realistic context improved patients' performance. However, specific impairments were observed in patients in the execution condition, namely actions slips, omissions, failure in initiating actions and purposeless displacements. Moreover, an analysis of planning time showed that, differently of the patients group, normal subjects spent more time during plan execution as compared to plan generation. These results suggest that after a frontal lobe lesion a defective formulation of a routine plan might affect the execution of the corresponding course of actions.

Script knowledge after severe traumatic brain injury.

Severe diffuse traumatic brain injury (TBI) may impair the performance of daily-life complex activities. The aim of the present study was to assess whether these difficulties are related to a representational impairment of action knowledge. Two tasks requiring the manipulation of scripts were used. The first (script reconstitution) required subjects to sort cards describing actions belonging to 4 different scripts, presented in a random order. The second (script generation) required subjects to generate actions belonging to a given script. The results showed that TBI patients had preserved access to goal representation and action knowledge. However, they demonstrated (1) significant impairments when they had to deal with simultaneous competing sources of information and (2) a lack of inhibitory control on routine overlearned skills. Patients' performance was significantly correlated with behavioral modifications in everyday life. These data suggest that action impairment in severe TBI patients cannot be attributed to an impairment of action knowledge per se. As previously suggested by Schwartz et al., a restriction of limited-capacity processing resources may account for the observed deficits.

Partially overlapping neural networks for real and imagined hand movements.

Neuroimagery findings have shown similar cerebral networks associated with imagination and execution of a movement. On the other hand, neuropsychological studies of parietal-lesioned patients suggest that these networks may be at least partly distinct. In the present study, normal subjects were asked to either imagine or execute auditory-cued hand movements. Compared with rest, imagination and execution showed overlapping networks, including bilateral premotor and parietal areas, basal ganglia and cerebellum. However, direct comparison between the two experimental conditions showed that specific cortico-subcortical areas were more engaged in mental simulation, including bilateral premotor, prefrontal, supplementary motor and left posterior parietal areas, and the caudate nuclei. These results suggest that a specific neuronal substrate is involved in the processing of hand motor representations.

Differential amygdala responses to winning and losing: a functional magnetic resonance imaging study in humans.

The amygdala has been shown to respond to many distinct types of affective stimuli, including reward and punishment feedback in animals. In humans, winning and losing situations can be considered as reward and punishment experiences, respectively. In this study, we used functional magnetic resonance imaging (fMRI) to measure regional brain activity when human subjects were given feedback on their performance during a simple response time task in a fictitious competitive tournament. Lexical stimuli were used to convey positive 'win' or negative 'lose' feedback. The frequency of positive and negative trials was parametrically varied by the experimenters independently from the subjects' actual performance and unbeknownst to them. The results showed that the parametric increase of winning was associated with left amygdala activation whereas the parametric increase of losing was associated with right amygdala activation. These findings provide functional evidence that the human amygdala differentially responds to changes in magnitude of positive or negative reinforcement conveyed by lexical stimuli.

How patients with Parkinson's disease retrieve and manage cognitive event knowledge.

Several studies have pointed out that basal ganglia are involved in adaptive control of action at both motor and cognitive level. This study aimed to investigate how basal ganglia retrieve and manage script event knowledge required in planning behavior. Script event knowledge was investigated in patients with Parkinson's Disease using three kinds of activity that differed in familiarity. Unlike patients with prefrontal lesions, patients with Parkinson's Disease were able to order events in a typical sequence and obeyed the boundaries and hierarchies between events. In contrast, patients with Parkinson's Disease were impaired in evaluating how important each script event was within the context of goal-oriented planning activity. Our findings indicate that the prefrontal cortex and the basal ganglia are differentially involved in planning. The role of the basal ganglia might consist in providing a feedback about the goodness of each action while building up meaningful sequences of events during learning.