A regional strategy to decrease the time to thrombectomy in patients with low probability of treatment by thrombolysis.

BACKGROUND AND PURPOSE: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC). METHODS: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups. RESULTS: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19). CONCLUSIONS: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories.

Distinct adaptation patterns between grip dynamics and arm kinematics when the body is upside-down.

In humans, practically all movements are learnt and performed in a constant gravitational field. Yet, studies on arm movements and object manipulation in parabolic flight have highlighted very fast sensorimotor adaptations to altered gravity environments. Here, we wondered if the motor adjustments observed in those altered gravity environments could also be observed on Earth in a situation where the body is upside-down. To address this question, we asked participants to perform rhythmic arm movements in two different body postures (right-side-up and upside-down) while holding an object in precision grip. Analyses of grip-load force coordination and of movement kinematics revealed distinct adaptation patterns between grip and arm control. Grip force and load force were tightly synchronized from the first movements performed in upside-down posture, reflecting a malleable allocentric grip control. In contrast, velocity profiles showed a more progressive adaptation to the upside-down posture and reflected an egocentric planning of arm kinematics. In addition to suggesting distinct mechanisms between grip dynamics and arm kinematics for adaptation to novel contexts, these results also suggest the existence of general mechanisms underlying gravity-dependent motor adaptation that can be used for fast sensorimotor coordination across different postures on Earth and, incidentally, across different gravitational conditions in parabolic flights, in human centrifuges, or in Space.NEW & NOTEWORTHY During rhythmic arm movements performed in an upside-down posture, grip control adapted very quickly, but kinematics adaptation was more progressive. Our results suggest that grip control and movement kinematics planning might operate in different reference frames. Moreover, by comparing our results with previous results from parabolic flight studies, we propose that a common mechanism underlies adaptation to unfamiliar body postures and adaptation to altered gravity.

Will MRI replace the EEG for the diagnosis of nonconvulsive status epilepticus, especially focal?

Magnetic resonance imaging (MRI) can now be used to diagnose or to provide confirmation of focal nonconvulsive status epilepticus (NCSE). Approximately half of patients with status epilepticus (SE) have signal changes. MRI can also aid in the differential diagnosis with generalized NCSE when there is a clinical or EEG doubt, e.g. with metabolic/toxic encephalopathies or Creutzfeldt-Jakob disease. With the development of stroke centers, MRI is available 24h/24 in most hospitals. MRI has a higher spatial resolution than electroencephalography (EEG). MRI with hyperintense lesions on FLAIR and DWI provides information related to brain activity over a longer period of time than a standard EEG where only controversial patterns like lateralized periodic discharges (LPDs) may be recorded. MRI may help identify the ictal nature of LPDs. The interpretation of EEG tracings is not easy, with numerous pitfalls and artifacts. Continuous video-EEGs require a specialized neurophysiology unit. The learning curve for MRI is better than for EEG. It is now easy to transfer MRI to a platform with expertise. MRI is more accessible than single photon emission computed tomography (SPECT) or positron emission tomography (PET). For the future, it is more interesting to develop a strategy with MRI than SPECT or PET for the diagnosis of NCSE. With the development of artificial intelligence, MRI has the potential to transform the diagnosis of SE. Additional MRI criteria beyond the classical clinical/EEG criteria of NCSE (rhythmic versus periodic, spatiotemporal evolution of the pattern…) should now be systematically added. However, it is more complicated to move patients to MRI than to perform an EEG in the intensive care unit, and at this time, we do not know how long the signal changes persist after the end of the SE. Studies with MRI at fixed intervals and after SE cessation are necessary.

Robustness of Controlled Release Tablets Based on a Cross-linked Pregelatinized Potato Starch Matrix.

The aim of this study was to evaluate the potential of a cross-linked pregelatinized potato starch (PREGEFLO® PI10) as matrix former for controlled release tablets. Different types of tablets loaded with diprophylline, diltiazem HCl or theophylline were prepared by direct compression of binary drug/polymer blends. The drug content was varied from 20 to 50%. Two hydroxypropyl methylcellulose grades (HPMC K100LV and K100M) were studied as alternative matrix formers. Drug release was measured in a variety of release media using different types of experimental set-ups. This includes 0.1 N HCl, phosphate buffer pH 6.8 and water, optionally containing different amounts of NaCl, sucrose, ethanol or pancreatin, fasted state simulated gastric fluid, fed state simulated gastric fluid, fasted state simulated intestinal fluid, fed state simulated intestinal fluid as well as media simulating the conditions in the colon of healthy subjects and patients suffering from Crohn's disease. The USP apparatuses I/II/III were used under a range of operating conditions and optionally coupled with the simulation of additional mechanical stress. Importantly, the drug release kinetics was not substantially affected by the investigated environmental conditions from tablets based on the cross-linked pregelatinized potato starch, similar to HPMC tablets. However, in contrast to the latter, the starch-based tablets roughly kept their shape upon exposure to the release media (they "only" increased in size) during the observation period, and the water penetration into the systems was much less pronounced. Thus, the investigated cross-linked pregelatinized potato starch offers an interesting potential as matrix former in controlled release tablets.

Multisensory components of rapid motor responses to fingertip loading.

Tactile and muscle afferents provide critical sensory information for grasp control, yet the contribution of each sensory system during online control has not been clearly identified. More precisely, it is unknown how these two sensory systems participate in online control of digit forces following perturbations to held objects. To address this issue, we investigated motor responses in the context of fingertip loading, which parallels the impact of perturbations to held objects on finger motion and fingerpad deformation, and characterized surface recordings of intrinsic (first dorsal interosseous, FDI) and extrinsic (flexor digitorum superficialis, FDS) hand muscles based on statistical modeling. We designed a series of experiments probing the effects of peripheral stimulation with or without anesthesia of the finger, and of task instructions. Loading of the fingertip generated a motor response in FDI at ~60 ms following the perturbation onset, which was only driven by muscle stretch, as the ring-block anesthesia reduced the gain of the response occurring later than 90 ms, leaving responses occurring before this time unaffected. In contrast, the motor response in FDS was independent of the lateral motion of the finger. This response started at ~90 ms on average and was immediately adjusted to task demands. Altogether these results highlight how a rapid integration of partially distinct sensorimotor circuits supports rapid motor responses to fingertip loading.NEW & NOTEWORTHY To grasp and manipulate objects, the brain uses touch signals related to skin deformation as well as sensory information about motion of the fingers encoded in muscle spindles. Here we investigated how these two sensory systems contribute to feedback responses to perturbation applied to the fingertip. We found distinct response components, suggesting that each sensory system engages separate sensorimotor circuits with distinct functions and latencies.

Regulation of diapause in carnivores.

Embryonic diapause is an evolutionary strategy to ensure that offspring are born when maternal and environmental conditions are optimal for survival. In many species of carnivores, obligate embryonic diapause occurs in every gestation. In mustelids, the regulation of diapause and reactivation is influenced by photoperiod, which then acts to regulate the secretion of pituitary prolactin. Prolactin in turn regulates ovarian steroid function. Reciprocal embryo transplant studies indicate that this state of embryonic arrest is conferred by uterine conditions and is presumed to be due to a lack of specific factors necessary for continued development. Studies of global gene expression in the mink (Neovison vison) revealed reduced expression of a cluster of genes that regulate the abundance of polyamines in the uterus during diapause, including the rate-limiting enzyme in polyamine production, ornithine decarboxylase (ODC). In addition, in this species, in vivo inhibition of the conversion of ornithine to the polyamine, putrescine, induces a reversible arrest in embryonic development and an arrest in both trophoblast and inner cell mass proliferation in vitro. Putrescine, at 0.5, 2 and 1,000 µM concentrations induced reactivation of mink embryos in culture, indicated by an increase in embryo volume, observed within five days. Further, prolactin induces ODC1 expression in the uterus, thereby regulating uterine polyamine levels. These results indicate that pituitary prolactin acts on ovarian and uterine targets to terminate embryonic diapause. In summary, our findings suggest that the polyamines, with synthesis under the control of pituitary prolactin, are the uterine factor whose absence is responsible for embryonic diapause in mustelid carnivores.

Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: The PROOF cohort.

OBJECTIVES: The aim of this study was to determine whether cognitive reserve in the elderly affects the evolution of cognitive performance and what its relationship is with active lifestyles in later life. METHODS: Cognitive performance was evaluated at baseline and 8 years later in 543 participants of the PROOF cohort, initially aged 67 years. Subjects were categorized as Cognitively Elite (CE), Cognitively Normal (CN) or Cognitively Impaired (CI) at each evaluation. At follow-up, demographic data and lifestyle, including social, intellectual and physical behaviors, were collected by questionnaires. RESULTS: As much as 69% (n=375) remained unchanged, while 25.5% (n=138) decreased and 5.5% (n=30) improved. When present, the reduction in cognitive status was most often limited to one level, but was dependent on the initial level, affecting up to 73% of the initially CN, but only 58% of the initially CE. Cognitive stability was significantly associated with the degree of social engagement at follow-up (CE: P=0.009; CN: P=0.025). CONCLUSION: In the healthy elderly, high cognitive ability predicts both cognitive ability and social involvement in later life. Cognitive decline by only one level may also extend the time to reach impairment, underlining the importance of the so-called cognitive reserve.

Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas.

BACKGROUND: A promising therapeutic approach for aggressive B-cell Non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL) is to target kinases involved in signal transduction and gene regulation. PIM1/2 serine/threonine kinases are highly expressed in activated B-cell-like DLBCL (ABC-DLBCL) with poor prognosis. In addition, both PIM kinases have a reported synergistic effect with c-MYC in mediating tumour development in several cancers, c-MYC gene being translocated to one of the immunoglobulin loci in nearly all BLs. METHODS: For these reasons, we tested the efficiency of several PIM kinase inhibitors (AZD1208, SMI4a, PIM1/2 inhibitor VI and Quercetagetin) in preventing proliferation of aggressive NHL-derived cell lines and compared their efficiency with PIM1 and/or PIM2 knockdown. RESULTS: We observed that most of the anti-proliferative potential of these inhibitors in NHL was due to an off-target effect. Interestingly, we present evidence of a kinase-independent function of PIM2 in regulating cell cycle. Moreover, combining AZD1208 treatment and PIM2 knockdown additively repressed cell proliferation. CONCLUSION: Taken together, this study suggests that at least a part of PIM1/2 oncogenic potential could be independent of their kinase activity, justifying the limited anti-tumorigenic outcome of PIM-kinase inhibitors in NHL.

Inertial torque during reaching directly impacts grip-force adaptation to weightless objects.

A hallmark of movement control expressed by healthy humans is the ability to gradually improve motor performance through learning. In the context of object manipulation, previous work has shown that the presence of a torque load has a direct impact on grip-force control, characterized by a significantly slower grip-force adjustment across lifting movements. The origin of this slower adaptation rate remains unclear. On the one hand, information about tangential constraints during stationary holding may be difficult to extract in the presence of a torque. On the other hand, inertial torque experienced during movement may also potentially disrupt the grip-force adjustments, as the dynamical constraints clearly differ from the situation when no torque load is present. To address the influence of inertial torque loads, we instructed healthy adults to perform visually guided reaching movements in weightlessness while holding an unbalanced object relative to the grip axis. Weightlessness offered the possibility to remove gravitational constraints and isolate the effect of movement-related feedback on grip force adjustments. Grip-force adaptation rates were compared with a control group who manipulated a balanced object without any torque load and also in weightlessness. Our results clearly show that grip-force adaptation in the presence of a torque load is significantly slower, which suggests that the presence of torque loads experienced during movement may alter our internal estimates of how much force is required to hold an unbalanced object stable. This observation may explain why grasping objects around the expected location of the center of mass is such an important component of planning and control of manipulation tasks.

Gravity-dependent estimates of object mass underlie the generation of motor commands for horizontal limb movements.

Moving requires handling gravitational and inertial constraints pulling on our body and on the objects that we manipulate. Although previous work emphasized that the brain uses internal models of each type of mechanical load, little is known about their interaction during motor planning and execution. In this report, we examine visually guided reaching movements in the horizontal plane performed by naive participants exposed to changes in gravity during parabolic flight. This approach allowed us to isolate the effect of gravity because the environmental dynamics along the horizontal axis remained unchanged. We show that gravity has a direct effect on movement kinematics, with faster movements observed after transitions from normal gravity to hypergravity (1.8g), followed by significant movement slowing after the transition from hypergravity to zero gravity. We recorded finger forces applied on an object held in precision grip and found that the coupling between grip force and inertial loads displayed a similar effect, with an increase in grip force modulation gain under hypergravity followed by a reduction of modulation gain after entering the zero-gravity environment. We present a computational model to illustrate that these effects are compatible with the hypothesis that participants partially attribute changes in weight to changes in mass and scale incorrectly their motor commands with changes in gravity. These results highlight a rather direct internal mapping between the force generated during stationary holding against gravity and the estimation of inertial loads that limb and hand motor commands must overcome.

[Ignored homicides]. / Homicides ignorés.

Forensic medicine is a fundamental science for a good evolution of the law and a serious protection of citizens. This science is also inextricably linked to public health. As basic discipline, we consider useful to revisit homicides which escape the investigators'sagacity and especially to know the reasons of this missing. Forensic high quality depends on respect of the crime scene, through specialized training and above all the recognition of this crucial discipline in our contemporary society.

Adaptive control of grip force to compensate for static and dynamic torques during object manipulation.

Manipulating a cup by the handle requires compensating for the torque induced by the moment of the mass of the cup relative to the location of the handle. In the present study, we investigated the control strategy of subjects asked to perform grip-lift movements with an object with center of mass located away from the grip axis. Participants were asked to lift the manipulandum with a two-fingers precision grip and stabilize it in front of a visual target. Subjects showed a gradual and slow adaptation of the grip-force scaling across trials: the grip force tended to decrease slowly, and the temporal coordination between grip-force and load-torque rates displayed gradually, better-coordinated patterns. Importantly, this adaptation was much slower than the stabilization of the same parameters measured either when no torque came into play or after previous adaptation to the presence of a torque. In contrast, the maximum rotation induced by the torque was controlled efficiently after only few trials, and an unexpected decrease in the tangential torque produced significant overcompensation. An unexpected increase in torque produced a consistent opposite effect. This shows that the compensation for the dynamic torque was based on an anticipatory, dynamic counter-torque produced by the arm and wrist motor commands. The comparatively slow stabilization of grip-force control suggests a specific adaptation process engaged by the presence of the torque. This paradigm, including tangential torques, clearly constitutes a powerful tool to extract the adaptive component of grip control during object manipulation.

Determinants of uptake, short-term and continued use of insecticide-treated curtains and jar covers for dengue control.

OBJECTIVE: To evaluate the acceptance and long-term use of insecticide-treated (IT) materials for dengue vector control. METHODS: In 2007, IT jar covers and/or curtains (PermaNet®) were distributed under routine conditions to 4101 households (10 clusters) in Venezuela and to 2032 households (22 clusters) in Thailand. The use of IT tools was measured at distribution (uptake), at 5/6 months (short-term use) and at 18/22 months (continued use) after distribution. Determinants of use were assessed with logistic regression analysis. RESULTS: The uptake of IT curtains was 76.7% in Venezuela and 92.3% in Thailand. It was associated with being a resident for >5 years (OR Venezuela 3.0 95% CI 2.0-4.4; OR Thailand 3.5 95% CI 1.7-7.3) and with pre-intervention use of ordinary curtains (OR Venezuela 2.2 95% CI 1.4-3.6). The continued use decreased significantly to 38.4% of households in Venezuela and 59.7% in Thailand and was, conditional on short-term use, only determined by the perceived effectiveness of IT curtains (OR Venezuela 13.0 95%CI 8.7-19.5; OR Thailand 4.9 95% CI 3.1-7.8). Disease knowledge and pre-intervention perception of mosquito nuisance were not associated with IT curtains' uptake or use. The uptake of IT jar covers in Venezuela was 21.5% and essentially determined by the presence of uncovered jars in the household (OR 32.5 95% CI 14.5-72.6). Their continued use, conditional on short-time use, was positively associated with the household use of Abate® (OR 7.8 95% CI 2.1-28.9). CONCLUSION: The use of IT curtains rapidly declines over time. Continued use is mainly determined by the perceived effectiveness of the tool. This poses a real challenge if IT curtains are to be introduced in dengue control programmes.

Optimal Duration of MRI Follow-up to Safely Identify Middle Ear Residual Cholesteatoma.

BACKGROUND AND PURPOSE: Previous studies have demonstrated the usefulness of non-EPI DWI for detection of residual cholesteatoma. However, limited data are available to determine the suitable duration of imaging follow-up after a first MR imaging with normal findings has been obtained. The present study aimed to determine the optimal duration of non-EPI DWI follow-up for residual cholesteatoma. MATERIALS AND METHODS: A retrospective, monocentric study was performed between 2013 and 2019 and included all participants followed up after canal wall up tympanoplasty with at least 2 non-EPI DWI examinations performed on the same 1.5T MR imaging scanner. MR images were reviewed independently by 2 radiologists. Sensitivity and specificity values were calculated as a function of time after the operation. Receiver operating characteristic curves were analyzed to determine the optimal follow-up duration. RESULTS: We analyzed 47 MRIs from 17 participants. At the end of the individual follow-up period, a residual cholesteatoma had been found in 41.1% of cases. The follow-up duration ranged from 20 to 198 months (mean, 65.9 [SD, 43.9] months). Participants underwent between 2 and 5 non-EPI DWI examinations. Analyses of the receiver operating characteristic curves revealed that the optimal diagnostic value of non-EPI DWI occurred 56 months after the operation when the first MR imaging performed a mean of 17.3 (SD, 6.8) months after the operation had normal findings (sensitivity = 0.71; specificity = 0.7, Youden index = 0.43). CONCLUSIONS: Repeat non-EPI DWI is required to detect slow-growing middle ear residual cholesteatomas. We, therefore, recommend performing non-EPI DWI for at least the first 5 years after the initial operation.

Flow-Diversion Treatment for Unruptured ICA Bifurcation Aneurysms with Unfavorable Morphology for Coiling.

BACKGROUND AND PURPOSE: Few reports described flow diversion for ICA bifurcation aneurysms. Our aim was to provide further insight into flow diversion for ICA bifurcation aneurysms difficult to treat with other strategies. MATERIALS AND METHODS: Consecutive patients receiving flow diverters for unruptured ICA bifurcation aneurysms were collected. Aneurysm occlusion (O'Kelly-Marotta grading scale) and clinical outcomes were evaluated. RESULTS: Twenty saccular ICA bifurcation aneurysms were treated with the Pipeline Embolization Device deployed from the M1 to the ICA, covering the aneurysm and the A1 segment. All patients presented with an angiographic visualized contralateral flow from the anterior communicating artery. Mean aneurysm size was 6.5 (SD, 3.2) mm (range, 4.5-20 mm). All lesions had an unfavorable dome-to-neck ratio (mean/median, 1.6/1.6; range, 0.8-2.8; interquartile range = 0.5) or aspect ratio for coiling (mean/median = 1.5/1.55; range, 0.8-2.5; interquartile range = 0.6). One was a very large aneurysm (20 mm). Nineteen medium-sized lesions were completely occluded during the angiographic follow-up (13 months). No cases of aneurysm rupture or retreatment were reported. No adverse events were described. Aneurysm occlusion was associated with the asymptomatic flow modification of the covered A1 that was occluded and contralaterally filled among 10 patients (50%), narrowed among 9 patients (45%), and unchanged in 1 subject (5%). There was no difference in the mean initial diameter of the occluded (2.1 [SD 0.4] mm; range, 1.6-3 mm) and narrowed (2 [SD, 0.2] mm; range, 1.7-2.6 mm) A1 segments. CONCLUSIONS: Medium-sized unruptured ICA bifurcation aneurysms with unfavorable morphology for coiling can be treated with M1 ICA flow diversion. Aneurysm occlusion is associated with flow modifications of the covered A1 that seems safe in the presence of a favorable collateral anatomy through the anterior communicating artery complex.

Prevalence of carotid web in a French cohort of cryptogenic stroke.

BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.

Influence of operator experience on the technical and clinical results of Woven EndoBridge endovascular treatment for intracranial aneurysms.

BACKGROUND & PURPOSE: The safety and efficacy of the Woven EndoBridge (WEB) device has been proven in recent multicenter trials. This study investigated whether operator experience influences WEB treatment-related outcomes. MATERIAL AND METHODS: This was a retrospective analysis of a prospectively collected multicenter database. The data of all patients who underwent WEB treatment for an intracranial aneurysm from March 2014 to June 2020 in two high-volume centers were pooled. Operator experience was indexed by the number of WEB treatments performed previously. The primary endpoint was the overall complication rate. Secondary endpoints were long-term adequate (Raymond-Roy classification of 1-2.) angiographic occlusion, WEB-related complications, number of WEB not deployed, procedure duration, and radiation exposure (air kerma). RESULTS: Among 237 patients (mean age 59.4 +/- 11.5 years) treated with WEB (median aneurysm diameter, 5.8 mm; interquartile range 4.5-7 mm), WEB-related complications occurred in 28 patients (11.8%) and adequate long-term occlusion was achieved for 154 aneurysms (86%). The median number of WEB treatment performed previously per operator was 20 (IQR, 9-41). The overall complication rate, WEB-related complication rate and aneurysm occlusion rate were not significantly correlated with WEB operator experience. There were also no significant correlations between the WEB operator experience and the number of WEB not deployed, procedure duration or radiation exposure. CONCLUSION: There was no significant association between the number of WEB treatments previously performed per operator and any technical or clinical results after intracranial aneurysm treatment with WEB. These results imply a relatively short learning curve for this device in high-volume neurovascular centers.

Fingertip moisture is optimally modulated during object manipulation.

Coordination between the normal force exerted by fingers on a held object and the tangential constraints at the fingertips helps to successfully manipulate objects. It is well established that the minimal grip force required to prevent an object from slipping strongly depends on the frictional properties at the finger-object interface. Moreover, interindividual variation in the modulation of grip force suggests that the moisture level of the skin could influence grip force strategy. In the present study we asked subjects to perform a horizontal point-to-point task holding an object with a precision grip. The object was equipped with a moisture sensor. We found large inter- and intraindividual moisture level variations. There was a strong correlation between grip force exerted and moisture level at the fingertips. Indeed, the grip force was minimal when the fingertip moisture was optimal with respect to friction. Furthermore, fingertip moisture tended toward this optimal level at which grip force is minimal. In conclusion, we showed a modulation of the grip force with moisture level and hypothesized novel mechanisms of moisture regulation that tend to stabilize the moisture level toward the value that minimizes grip force.

Saccadic compensation for smooth eye and head movements during head-unrestrained two-dimensional tracking.

Spatial updating is the ability to keep track of the position of world-fixed objects while we move. In the case of vision, this phenomenon is called spatial constancy and has been studied in head-restraint conditions. During head-restrained smooth pursuit, it has been shown that the saccadic system has access to extraretinal information from the pursuit system to update the objects' position in the surrounding environment. However, during head-unrestrained smooth pursuit, the saccadic system needs to keep track of three different motor commands: the ocular smooth pursuit command, the vestibuloocular reflex (VOR), and the head movement command. The question then arises whether saccades compensate for these movements. To address this question, we briefly presented a target during sinusoidal head-unrestrained smooth pursuit in darkness. Subjects were instructed to look at the flash as soon as they saw it. We observed that subjects were able to orient their gaze to the memorized (and spatially updated) position of the flashed target generally using one to three successive saccades. Similar to the behavior in the head-restrained condition, we found that the longer the gaze saccade latency, the better the compensation for intervening smooth gaze displacements; after about 400 ms, 62% of the smooth gaze displacement had been compensated for. This compensation depended on two independent parameters: the latency of the saccade and the eye contribution to the gaze displacement during this latency period. Separating gaze into eye and head contributions, we show that the larger the eye contribution to the gaze displacement, the better the overall compensation. Finally, we found that the compensation was a function of the head oscillation frequency and we suggest that this relationship is linked to the modulation of VOR gain. We conclude that the general mechanisms of compensation for smooth gaze displacements are similar to those observed in the head-restrained condition.

Movement stability under uncertain internal models of dynamics.

Sensory noise and feedback delay are potential sources of instability and variability for the on-line control of movement. It is commonly assumed that predictions based on internal models allow the CNS to anticipate the consequences of motor actions and protect the movements from uncertainty and instability. However, during motor learning and exposure to unknown dynamics, these predictions can be inaccurate. Therefore a distinct strategy is necessary to preserve movement stability. This study tests the hypothesis that in such situations, subjects adapt the speed and accuracy constraints on the movement, yielding a control policy that is less prone to undesirable variability in the outcome. This hypothesis was tested by asking subjects to hold a manipulandum in precision grip and to perform single-joint, discrete arm rotations during short-term exposure to weightlessness (0 g), where the internal models of the limb dynamics must be updated. Measurements of grip force adjustments indicated that the internal predictions were altered during early exposure to the 0 g condition. Indeed, the grip force/load force coupling reflected that the grip force was less finely tuned to the load-force variations at the beginning of the exposure to the novel gravitational condition. During this learning period, movements were slower with asymmetric velocity profiles and target undershooting. This effect was compared with theoretical results obtained in the context of optimal feedback control, where changing the movement objective can be directly tested by adjusting the cost parameters. The effect on the simulated movements quantitatively supported the hypothesis of a change in cost function during early exposure to a novel environment. The modified optimization criterion reduces the trial-to-trial variability in spite of the fact that noise affects the internal prediction. These observations support the idea that the CNS adjusts the movement objective to stabilize the movement when internal models are uncertain.