Stimulation of frontal pathways disrupts hand muscle control during object manipulation.

The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an 'arrest' pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a 'clumsy' pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

Association of 7-Day Profiles of Motor Activity in Marital Dyads with One Component Affected by Parkinson's Disease.

(1) Background: A noticeable association between the motor activity (MA) profiles of persons living together has been found in previous studies. Social actigraphy methods have shown that this association, in marital dyads composed of healthy individuals, is greater than that of a single person compared to itself. This study aims at verifying the association of MA profiles in dyads where one component is affected by Parkinson's disease (PD). (2) Methods: Using a wearable sensor-based social actigraphy approach, we continuously monitored, for 7 days, the activities of 27 marital dyads including one component with PD. (3) Results: The association of motor activity profiles within a marital dyad (cross-correlation coefficient 0.344) is comparable to the association of any participant with themselves (0.325). However, when considering the disease severity quantified by the UPDRS III score, it turns out that the less severe the symptoms, the more associated are the MA profiles. (4) Conclusions: Our findings suggest that PD treatment could be improved by leveraging the MA of the healthy spouse, thus promoting lifestyles also beneficial for the component affected by PD. The actigraphy approach provided valuable information on habitual functions and motor fluctuations, and could be useful in investigating the response to treatment.

Motor impairment evoked by direct electrical stimulation of human parietal cortex during object manipulation.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)-lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

2-O-Acetyl-3,4,5,6-tetra-O-benzyl-d-myo-inosityl diphenylphosphate: A new useful intermediate to inositol phosphate and phospholipids.

Inositol phosphates and inositol phospholipids are ubiquitous in biochemistry and play a central role in cell signaling and regulation events. For this reason, their synthesis has attracted widespread interest. This paper describes the preparation of a new optically active inositol phosphate derivative, 2-O-acetyl-3,4,5,6-tetra-O-benzyl-d-myo-inosityl diphenylphosphate (6), and its characterization by spectroscopic methods. Compound (6) represents a useful intermediate for the preparation of inositol phosphate and phospholipids, in particular of glycerophosphoinositol (GPI), a natural anti-inflammatory agent.

Gait disorders in CKD patients: muscle wasting or cognitive impairment? A cross-sectional pilot study to investigate gait signatures in Stage 1-5 CKD patients.

BACKGROUND: Instrumental gait analysis in nephrology is widely neglected, although patients with chronic kidney disease (CKD) show brain changes due to cerebrovascular disease and metabolic disorders that can potentially influence gait quality. Our study assesses the association between CKD stages and gait parameters, to understand the prevalent status of brain related gait parameters (i.e. variability) and of performance related parameters (i.e. gait speed, stride length). We hypothesize that gait changes are detectable already in early stages of CKD. METHODS: Forty-five participants distributed in 5 CKD severity groups underwent an instrumental gait analysis via a triaxial accelerometer affixed to the lower trunk under single- and dual-task conditions. In addition to spatio-temporal parameters, variability and dual-task cost of gait were extracted. A battery of clinical assessments was conducted with the aim of helping to better explain the findings of the gait analysis. A correlation analysis was made to investigate a linear relation between gait parameters and CKD severity. RESULTS: Statistically significant correlations (Pearson correlation coefficient) with CKD severity were found for gait speed (p < 0.01, r = -0.55, 95% CI [-0.73;-0.30]), stride length ( p < 0.01, r = -0.40, 95% CI [-0.62;-0.12]), step length (p < 0.01, r = -0.41, 95% CI [-0.63;-0.13], coefficient of variance (CV) of step length (p = 0.01, r = 0.36, 95% CI [0.08;0.59]), gait regularity (p < 0.01, r = -0.38, 95% CI [-0.61;-0.10]), dual-task cost of gait speed (p < 0.01, r = 0.40, 95% CI [0.13;0.62]) and dual-task cost of stride time (p = 0.03, r = 0.32, 95% CI [0.03;0.57]). Adjustment for age and gender confirmed all results except for gait regularity. With increasing severity of renal failure, Handgrip strength, Time for the Expanded Timed Get Up and Go test, executive functions, haemoglobin, and haematocrit, worsen. CONCLUSIONS: The correlation of CKD severity with spatio-temporal parameters (performance indices mainly relatable to peripheral functionality) and with variability of gait (related to central factors) supported by the results of the clinical assessments, suggests that gait disturbance in CKD patients is not only due to metabolic factors that lead to muscle wasting, but also to brain changes that affect motor control. This suggests that the treatment of renal disease should include cognitive aspects in addition to metabolic and functional factors.

To Live Together Is to Move Together: Social Actigraphy Applied to Healthy Elderly People.

(1) Background: Actigraphic methods allow prolonged monitoring of human physical activity (PA) by wearable sensors in a real-life unsupervised context. They generally do not characterize the social context, and nearby persons can have a modulating effect on the performed PA. The present study aims to apply an existing method for bimanual actigraphy to both components of a marital dyad to verify the level of association between the two PA profiles. Other dyad comparisons complete the overall figure. (2) Methods: Seven-day actigraphic recordings collected from both components of 20 married couples of retired, cohabiting, healthy subjects (age ranging from 58 to 87 years) were considered. (3) Results: PA profiles of a marital dyad are significantly more correlated (coefficient: 0.444) than unrelated couples (0.278). Interestingly, participants' profiles compared with their own recording shifted by 24 h, evidencing an intermediate level of association (0.335). Data from the literature, the high association (0.875) of individual right and left wrist profiles, enforce the analysis. (4) Conclusions: The proposed method, called "social actigraphy", confirmed that the partner has a relevant effect on one's PA profile, thus suggesting involving the partner in programs concerning lifestyle changes and patient rehabilitation.

Quantitative Assessment of Motor Neglect.

Background and Purpose: We used differential actigraphy as a novel, objective method to quantify motor neglect (a clinical condition whereby patients mimic hemiplegia even in the absence of sensorimotor deficits), whose diagnosis is at present highly subjective, based on the clinical observation of patients' spontaneous motor behavior. Methods: Patients wear wristwatch-like accelerometers, which record spontaneous motor activity of their upper limbs during 24 hours. Asymmetries of motor behavior are then automatically computed offline. On the basis of normal participants' performance, we calculated cutoff scores of left/right motor asymmetry. Results: Differential actigraphy showed contralesional motor neglect in 9 of 35 patients with unilateral strokes, consistent with clinical assessment. An additional patient with clinical signs of motor neglect obtained a borderline asymmetry score. Lesion location in a subgroup of 25 patients was highly variable, suggesting that motor neglect is a heterogenous condition. Conclusions: Differential actigraphy provides an ecological measure of spontaneous motor behavior, and can assess upper limb motricity in an objective and quantitative manner. It thus offers a convenient, cost-effective, and relatively automatized procedure for following-up motor behavior in neurological patients and to assess the effects of rehabilitation.

An overall framework for the E. coli γ-glutamyltransferase-catalyzed transpeptidation reactions.

γ-Glutamyl derivatives of proteinogenic or modified amino acids raise considerable interest as flavor enhancers or biologically active compounds. However, their supply, on a large scale and at reasonable costs, remains challenging. Enzymatic synthesis has been recognized as a possible affordable alternative with respect to both isolation procedures from natural sources, burdened by low-yield and by the requirement of massive amount of starting material, and chemical synthesis, inconvenient because of the need of protection/deprotection steps. The E. coli γ-glutamyltransferase (Ec-GGT) has already been proposed as a biocatalyst for the synthesis of various γ-glutamyl derivatives. However, enzymatic syntheses using this enzyme usually provide the desired products in limited yield. Hydrolysis and autotranspeptidation of the donor substrate have been identified as the side reactions affecting the final yield of the catalytic process. In addition, experimental conditions need to be specifically adjusted for each acceptor substrate. Substrate specificity and the fine characterization of the activities exerted by the enzyme over time has so far escaped rationalization. In this work, reactions catalyzed by Ec-GGT between the γ-glutamyl donor glutamine and several representative acceptor amino acids have been finely analyzed with the identification of single reaction products over time. This approach allowed to rationalize the effect of donor/acceptor molar ratio on the outcome of the transpeptidation reaction and on the distribution of the different byproducts, inferring a general scheme for Ec-GGT-catalyzed reactions. The propensity to react of the different acceptor substrates is in agreement with recent findings obtained using model substrates and further supported by x-ray crystallography and will contribute to characterize the still elusive acceptor binding site of the enzyme.

Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction.

Benzil reductases are dehydrogenases preferentially active on aromatic 1,2-diketones, but the reasons for this peculiar substrate recognition have not yet been clarified. The benzil reductase (KRED1-Pglu) from the non-conventional yeast Pichia glucozyma showed excellent activity and stereoselectivity in the monoreduction of space-demanding aromatic 1,2-dicarbonyls, making this enzyme attractive as biocatalyst in organic chemistry. Structural insights into the stereoselective monoreduction of 1,2-diketones catalyzed by KRED1-Pglu were investigated starting from its 1.77 Å resolution crystal structure, followed by QM and classical calculations; this study allowed for the identification and characterization of the KRED1-Pglu reactive site. Once identified the recognition elements involved in the stereoselective desymmetrization of bulky 1,2-dicarbonyls mediated by KRED1-Pglu, a mechanism was proposed together with an in silico prediction of substrates reactivity.

Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation.

Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.

Actigraphic Measurement of the Upper Limbs for the Prediction of Ischemic Stroke Prognosis: An Observational Study.

BACKGROUND: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. METHODS: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients' wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). RESULTS: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. CONCLUSIONS: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

Actigraphic measurement of the upper limbs movements in acute stroke patients.

BACKGROUND: Stroke units provide patients with a multiparametric monitoring of vital functions, while no instruments are actually available for a continuous monitoring of patients motor performance. Our aim was to develop an actigraphic index able both to identify the paretic limb and continuously monitor the motor performance of stroke patients in the stroke unit environment. METHODS: Twenty consecutive acute stroke patients (mean age 69.2 years SD 10.1, 8 males and 12 females) and 17 bed-restrained patients (mean age 70.5 years SD 7.3, 7 males and 10 females) hospitalized for orthopedic diseases of the lower limbs, but not experiencing neurological symptoms, were enrolled. This last group represented our control group. The motor activity of arms was recorded for 24 h using two programmable actigraphic systems showing off as wrist-worn watches. The firmware segmented the acquisition in epochs of 1 minute and for each epoch calculates two motor activity indices: MAe1 (Epoch-related Motor Activity index) and MAe2 (Epoch-related Motor Activity index 2). MAe1 is defined as the standard deviation of the acceleration module and MAe2 as the module of the standard deviation of acceleration components. To describe the 24 h motor performance of each limb, we calculated the mean value of MAe1 and MAe2 (respectively MA1_24h and MA2_24h). Then we obtained two Asymmetry Rate Indices: AR1_24h and AR2_24h to show the motor activity prevalence. AR1_24h refers to the asymmetry index between the values of MAe1 of both arms and AR2_24h to MAe2 values. The stroke patients were clinically evaluated by NIHSS at the beginning (NIHSST0) and at the end (NIHSST1) of the 24 h actigraphic recordings. RESULTS: Both MA1_24h and MA2_24h indices were smaller in the paretic than in the unaffected arm (respectively p = 0.004 and p = 0.004). AR2_24h showed a better capability (95% of paretic arms correctly identified, Phi Coefficient: 0.903) to discriminate the laterality of the clinical deficit than AR1_24h (85% of paretic arms correctly identified, Phi Coefficient: 0,698). We also found that AR1_24h did not differ between the two groups of patients while AR2_24h was greater in stroke patients than in controls and positively correlated with NIHSS total scores (r: 0.714, p < 0.001 for NIHSS, IC95%: 0.42-0.90) and with the sub-score relative to the paretic upper limb (r: 0.812, p < 0.001, IC95%: 0.62-0.96). CONCLUSIONS: Our data show that actigraphic monitoring of upper limbs can detect the laterality of the motor deficit and measure the clinical severity. These findings suggest that the above described actigraphic system could implement the existing multiparametric monitoring in stroke units.

Effects of Gait Strategy and Speed on Regularity of Locomotion Assessed in Healthy Subjects Using a Multi-Sensor Method.

The regularity of pseudo-periodic human movements, including locomotion, can be assessed by autocorrelation analysis of measurements using inertial sensors. Though sensors are generally placed on the trunk or pelvis, movement regularity can be assessed at any body location. Pathological factors are expected to reduce regularity either globally or on specific anatomical subparts. However, other non-pathological factors, including gait strategy (walking and running) and speed, modulate locomotion regularity, thus potentially confounding the identification of the pathological factor. The present study's objectives were (1) to define a multi-sensor method based on the autocorrelation analysis of the acceleration module (norm of the acceleration vector) to quantify regularity; (2) to conduct an experimental study on healthy adult subjects to quantify the effect on movement regularity of gait strategy (walking and running at the same velocity), gait speed (four speeds, lower three for walking, upper two for running), and sensor location (on four different body parts). Twenty-five healthy adults participated and four triaxial accelerometers were located on the seventh cervical vertebra (C7), pelvis, wrist, and ankle. The results showed that increasing velocity was associated with increasing regularity only for walking, while no difference in regularity was observed between walking and running. Regularity was generally highest at C7 and ankle, and lowest at the wrist. These data confirm and complement previous literature on regularity assessed on the trunk, and will support future analyses on individuals or groups with specific pathologies affecting locomotor functions.

Physical human-robot interaction of an active pelvis orthosis: toward ergonomic assessment of wearable robots.

BACKGROUND: In human-centered robotics, exoskeletons are becoming relevant for addressing needs in the healthcare and industrial domains. Owing to their close interaction with the user, the safety and ergonomics of these systems are critical design features that require systematic evaluation methodologies. Proper transfer of mechanical power requires optimal tuning of the kinematic coupling between the robotic and anatomical joint rotation axes. We present the methods and results of an experimental evaluation of the physical interaction with an active pelvis orthosis (APO). This device was designed to effectively assist in hip flexion-extension during locomotion with a minimum impact on the physiological human kinematics, owing to a set of passive degrees of freedom for self-alignment of the human and robotic hip flexion-extension axes. METHODS: Five healthy volunteers walked on a treadmill at different speeds without and with the APO under different levels of assistance. The user-APO physical interaction was evaluated in terms of: (i) the deviation of human lower-limb joint kinematics when wearing the APO with respect to the physiological behavior (i.e., without the APO); (ii) relative displacements between the APO orthotic shells and the corresponding body segments; and (iii) the discrepancy between the kinematics of the APO and the wearer's hip joints. RESULTS: The results show: (i) negligible interference of the APO in human kinematics under all the experimented conditions; (ii) small (i.e., < 1 cm) relative displacements between the APO cuffs and the corresponding body segments (called stability); and (iii) significant increment in the human-robot kinematics discrepancy at the hip flexion-extension joint associated with speed and assistance level increase. CONCLUSIONS: APO mechanics and actuation have negligible interference in human locomotion. Human kinematics was not affected by the APO under all tested conditions. In addition, under all tested conditions, there was no relevant relative displacement between the orthotic cuffs and the corresponding anatomical segments. Hence, the physical human-robot coupling is reliable. These facts prove that the adopted mechanical design of passive degrees of freedom allows an effective human-robot kinematic coupling. We believe that this analysis may be useful for the definition of evaluation metrics for the ergonomics assessment of wearable robots.

Drawing lines while imagining circles: Neural basis of the bimanual coupling effect during motor execution and motor imagery.

When people simultaneously draw lines with one hand and circles with the other hand, both trajectories tend to assume an oval shape, showing that hand motor programs interact (the so-called "bimanual coupling effect"). The aim of the present study was to investigate how motor parameters (drawing trajectories) and the related brain activity vary during bimanual movements both in real execution and in motor imagery tasks. In the 'Real' modality, subjects performed right hand movements (lines) and, simultaneously, Congruent (lines) or Non-congruent (circles) left hand movements. In the 'Imagery' modality, subjects performed only right hand movements (lines) and, simultaneously, imagined Congruent (lines) or Non-congruent (circles) left hand movements. Behavioral results showed a similar interference of both the real and the imagined circles on the actually executed lines, suggesting that the coupling effect also pertains to motor imagery. Neuroimaging results showed that a prefrontal-parietal network, mostly involving the pre-Supplementary Motor Area (pre-SMA) and the posterior parietal cortex (PPC), was significantly more active in Non-congruent than in Congruent conditions, irrespective of task (Real or Imagery). The data also confirmed specific roles of the right superior parietal lobe (SPL) in mediating spatial interference, and of the left PPC in motor imagery. Collectively, these findings suggest that real and imagined Non-congruent movements activate common circuits related to the intentional and predictive operation generating bimanual coupling, in which the pre-SMA and the PPC play a crucial role.

Analysis of relative displacement between the HX wearable robotic exoskeleton and the user's hand.

BACKGROUND: Advances in technology are allowing for the production of several viable wearable robotic devices to assist with activities of daily living and with rehabilitation. One of the most pressing limitations to user satisfaction is the lack of consistency in motion between the user and the robotic device. The displacement between the robot and the body segment may not correspond because of differences in skin and tissue compliance, mechanical backlash, and/or incorrect fit. FINDINGS: This report presents the results of an analysis of relative displacement between the user's hand and a wearable exoskeleton, the HX. HX has been designed to maximize comfort, wearability and user safety, exploiting chains with multiple degrees-of-freedom with a modular architecture. These appealing features may introduce several uncertainties in the kinematic performances, especially when considering the anthropometry, morphology and degree of mobility of the human hand. The small relative displacements between the hand and the exoskeleton were measured with a video-based motion capture system, while the user executed several different grips in different exoskeleton modes. CONCLUSIONS: The analysis furnished quantitative results about the device performance, differentiated among device modules and test conditions. In general, the global relative displacement for the distal part of the device was in the range 0.5-1.5 mm, while within 3 mm (worse but still acceptable) for displacements nearest to the hand dorsum. Conclusions over the HX design principles have been drawn, as well as guidelines for future developments.

Assessment of biofeedback rehabilitation in post-stroke patients combining fMRI and gait analysis: a case study.

BACKGROUND: The ability to walk independently is a primary goal for rehabilitation after stroke. Gait analysis provides a great amount of valuable information, while functional magnetic resonance imaging (fMRI) offers a powerful approach to define networks involved in motor control. The present study reports a new methodology based on both fMRI and gait analysis outcomes in order to investigate the ability of fMRI to reflect the phases of motor learning before/after electromyographic biofeedback treatment: the preliminary fMRI results of a post stroke subject's brain activation, during passive and active ankle dorsal/plantarflexion, before and after biofeedback (BFB) rehabilitation are reported and their correlation with gait analysis data investigated. METHODS: A control subject and a post-stroke patient with chronic hemiparesis were studied. Functional magnetic resonance images were acquired during a block-design protocol on both subjects while performing passive and active ankle dorsal/plantarflexion. fMRI and gait analysis were assessed on the patient before and after electromyographic biofeedback rehabilitation treatment during gait activities. Lower limb three-dimensional kinematics, kinetics and surface electromyography were evaluated. Correlation between fMRI and gait analysis categorical variables was assessed: agreement/disagreement was assigned to each variable if the value was in/outside the normative range (gait analysis), or for presence of normal/diffuse/no activation of motor area (fMRI). RESULTS: Altered fMRI activity was found on the post-stroke patient before biofeedback rehabilitation with respect to the control one. Meanwhile the patient showed a diffuse, but more limited brain activation after treatment (less voxels). The post-stroke gait data showed a trend towards the normal range: speed, stride length, ankle power, and ankle positive work increased. Preliminary correlation analysis revealed that consistent changes were observed both for the fMRI data, and the gait analysis data after treatment (R > 0.89): this could be related to the possible effects BFB might have on the central as well as on the peripheral nervous system. CONCLUSIONS: Our findings showed that this methodology allows evaluation of the relationship between alterations in gait and brain activation of a post-stroke patient. Such methodology, if applied on a larger sample subjects, could provide information about the specific motor area involved in a rehabilitation treatment.

Hydroxyapatite: An Eco-Friendly Material for Enzyme Immobilization.

Biocatalysis has emerged in the last decade as a valuable and eco-friendly tool in chemical synthesis, allowing in several instances to reduce or eliminate the use of hazardous reagents, environmentally dangerous solvents and harsh reaction conditions. Enzymes are indeed able to catalyse chemical transformations on non-natural substrates under mild reaction conditions, still maintaining their high chemo-, regio-, and stereoselectivity. Enzyme immobilization, i. e. the grafting of enzymes on solid supports, can be viewed as an enabling technology, as it allows a better control of the reaction and the recycling of the biocatalyst, thus rendering economically viable the use of expensive enzymes also on a large scale. To pursue a sustainable approach, the supports for enzyme immobilization should be eco-friendly and possibly renewable. This review highlights the use of hydroxyapatite (HAP), an inorganic biomaterial able to confer strength and stiffness to the bone tissue in animals, as carrier for enzyme immobilization. HAP is a cheap, non-toxic and biocompatible material, with high surface area and protein affinity. Different enzyme classes, immobilization strategies, and the use of diverse HAP-based supports will be discussed, underlining the immobilization conditions and the properties of the obtained biocatalysts.

'Moving' a paralysed hand: bimanual coupling effect in patients with anosognosia for hemiplegia.

Selective neurological impairments can shed light on different aspects of motor cognition. Brain-damaged patients with anosognosia for hemiplegia deny their motor deficit and believe they can still move the paralysed limb. Here we study, for the first time, if the anomalous subjective experience that their affected hand can still move, may have objective consequences that constrain movement execution with the opposite, intact hand. Using a bimanual motor task, in which anosognosic patients were asked to simultaneously trace out lines with their unaffected hand and circles with their paralysed hand, we found that the trajectories of the intact hand were influenced by the requested movement of the paralysed hand, with the intact hand tending to assume an oval trajectory (bimanual coupling effect). This effect was comparable to that of a group of healthy subjects who actually moved both hands. By contrast, brain-damaged patients with motor neglect or actual hemiplegia but no anosognosia did not show this bimanual constraint. We suggest that anosognosic patients may have intact motor intentionality and planning for the plegic hand. Rather than being merely an inexplicable confabulation, anosognosia for the plegic hand can produce objective constraints on what the intact hand does.

Changes of gait pattern in children with Charcot-Marie-Tooth disease type 1A: a 18 months follow-up study.

BACKGROUND: In a previous study we identified 3 different gait patterns in a group of children with CMT1A disease: Normal-like (NL), Foot-drop (FD), Foot-drop and Push-off Deficit (FD&POD). Goal of the present study was to perform a follow-up evaluation of the same group of patients to analyze possible changes of gait features in relation to disease progression or specific therapy. METHODS: Nineteen children with CMT1A were evaluated clinically (CMT-Examination Score and Overall Neuropathy Limitation Scale) and through gait analysis 18.2±1.5 months after a baseline evaluation. Meanwhile, 3 of them had foot surgery. RESULTS: Fifteen out of the 16 non-operated patients significantly changed at least one of the two parameters associated to primary signs (FD and/or POD). Eleven participants worsened at least one parameter and 9 improved one parameter. CMTES significantly worsened for the group of non-operated patients. However, there was no change in CMTES score in 4 patients and in ONLS score in 11. At subgroup level, participants originally belonging to NL group showed a trend towards a foot-drop deficit (-15%, ns); FD and FD&POD subgroups did not change their primary signs, although significant changes were identified individually. All 3 patients operated have improved push-off and proximal joint patterns during walking. Clinical scores did not change within any sub-group. CONCLUSIONS: Subtle changes occurring in 1.5 year in gait features of CMT1A children can be instrumentally identified. Such changes show a large inter-subject variability, with some patients even improving their walking pattern. There is anecdotal evidence that foot surgery may improve the push-off phase of gait.