Innovative Quantitative Assessment of Hand Function in Carpal Tunnel Syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) compromises fine sensorimotor function during activities of daily living and affects a large number of individuals with high burden costs for society. The purpose of this study was to quantitatively characterize fine movement skills in CTS patients preoperatively and at 1 month postoperatively by means of a sensor-engineered glove, in order to provide new insights for evaluative and finally therapeutic purposes. METHODS: Forty-one CTS patients and 41 age- and gender-matched healthy controls (HC) were analyzed by adopting the engineered glove Hand Test System (HTS), which previously demonstrated its reliability and sensitivity to detect hands dysfunction in several neurological diseases. A sub-group of 11 CTS subjects was re-tested 1 month after surgery. Three parameters-touch duration (TD), inter-tapping interval (ITI), and movement rate (MR)-were considered to characterize hand function. RESULTS: The affected hand of CTS patients generally showed worst finger opposition performances than HC. Comparing the dominant hand, all parameters were able to significantly discriminate CTS patients from HC. Considering the nondominant hand, the best performing parameter in discriminating CTS from HC was TD. The follow-up assessment at 1 month after surgery showed that considered parameters were able to monitor patients' recovery. In particular, the TD parameter recorded at the 3 different assigned task modalities resulted significantly enhanced. CONCLUSIONS: Results of this pilot study proved the validity of the parameters obtained through the sensor-engineered glove to assess objectively hand functional status and surgical outcomes in CTS.

Characteristics and Applications of Technology-Aided Hand Functional Assessment: A Systematic Review.

Technology-aided hand functional assessment has received considerable attention in recent years. Its applications are required to obtain objective, reliable, and sensitive methods for clinical decision making. This systematic review aims to investigate and discuss characteristics of technology-aided hand functional assessment and their applications, in terms of the adopted sensing technology, evaluation methods and purposes. Based on the shortcomings of current applications, and opportunities offered by emerging systems, this review aims to support the design and the translation to clinical practice of technology-aided hand functional assessment. To this end, a systematic literature search was led, according to recommended PRISMA guidelines, in PubMed and IEEE Xplore databases. The search yielded 208 records, resulting into 23 articles included in the study. Glove-based systems, instrumented objects and body-networked sensor systems appeared from the search, together with vision-based motion capture systems, end-effector, and exoskeleton systems. Inertial measurement unit (IMU) and force sensing resistor (FSR) resulted the sensing technologies most used for kinematic and kinetic analysis. A lack of standardization in system metrics and assessment methods emerged. Future studies that pertinently discuss the pathophysiological content and clinimetrics properties of new systems are required for leading technologies to clinical acceptance.

A multi-laboratory evaluation of microelectrode array-based measurements of neural network activity for acute neurotoxicity testing.

There is a need for methods to screen and prioritize chemicals for potential hazard, including neurotoxicity. Microelectrode array (MEA) systems enable simultaneous extracellular recordings from multiple sites in neural networks in real time and thereby provide a robust measure of network activity. In this study, spontaneous activity measurements from primary neuronal cultures treated with three neurotoxic or three non-neurotoxic compounds was evaluated across four different laboratories. All four individual laboratories correctly identifed the neurotoxic compounds chlorpyrifos oxon (an organophosphate insecticide), deltamethrin (a pyrethroid insecticide) and domoic acid (an excitotoxicant). By contrast, the other three compounds (glyphosate, dimethyl phthalate and acetaminophen) considered to be non-neurotoxic ("negative controls"), produced only sporadic changes of the measured parameters. The results were consistent across the different laboratories, as all three neurotoxic compounds caused concentration-dependent inhibition of mean firing rate (MFR). Further, MFR appeared to be the most sensitive parameter for effects of neurotoxic compounds, as changes in electrical activity measured by mean frequency intra burst (MFIB), and mean burst duration (MBD) did not result in concentration-response relationships for some of the positive compounds, or required higher concentrations for an effect to be observed. However, greater numbers of compounds need to be tested to confirm this. The results obtained indicate that measurement of spontaneous electrical activity using MEAs provides a robust assessment of compound effects on neural network function.

Microelectrode array (MEA) platform as a sensitive tool to detect and evaluate Ostreopsis cf. ovata toxicity.

In the last decade, the occurrence of harmful dinoflagellate blooms of the genus Ostreopsis has increased both in frequency and in geographic distribution with adverse impacts on public health and the economy. Ostreopsis species are producers of palytoxin-like toxins (putative palytoxin and ovatoxins) which are among the most potent natural non-protein compounds known to date, exhibiting extreme toxicity in mammals, including humans. Most existing toxicological data are derived from in vivo mouse assay and are related to acute effects of pure palytoxin, without considering that the toxicity mechanism of dinoflagellates can be dependent on the varying composition of complex biotoxins mixture and on the presence of cellular components. In this study, in vitro neuronal networks coupled to microelectrode array (MEA)-based system are proposed, for the first time, as sensitive biosensors for the evaluation of marine alga toxicity on mammalian cells. Toxic effect was investigated by testing three different treatments of laboratory cultured Ostreopsis cf. ovata cells: filtered and re-suspended algal cells; filtered, re-suspended and sonicated algal cells; conditioned growth medium devoid of algal cells. The great sensitivity of this system revealed the mixture of PTLX-complex analogues naturally released in the growth medium and the different potency of the three treatments to inhibit the neuronal network spontaneous electrical activity. Moreover, by means of the multiparametric analysis of neuronal network activity, the approach revealed a different toxicity mechanism of the cellular component compared to the algal conditioned growth medium, highlighting the potential active role of the first treatment.

An engineered glove for investigating the neural correlates of finger movements using functional magnetic resonance imaging.

Objective measurement of concomitant finger motor performance is recommended for functional magnetic resonance imaging (fMRI) studies investigating brain activity during finger tapping tasks, because performance modality and ability can influence the selection of different neural networks. In this study, we present a novel glove system for quantitative evaluation of finger opposition movements during fMRI (called Glove Analyzer for fMRI, GAF). Several tests for magnetic resonance (MR) compatibility were performed concerning magnet forces, image artifacts and right functioning of the system. Then, pilot fMRI of finger opposition tasks were conducted at 1.5T and 3T to investigate the neural correlates of sequences of finger opposition movements with the right hand, with simultaneous behavioral recording by means of GAF. All the MR compatibility tests succeeded, and the fMRI analysis revealed mainly the activation of the left sensorimotor areas and right cerebellum, regions that are known to be involved in finger movements. No artifactual clusters were detected in the activation maps. At the same time, through the parameters calculated by GAF it was possible to describe the sensorimotor strategy adopted by the subjects during the required task. Thus, the proposed device resulted to be MR compatible and can be useful for future fMRI studies investigating the neural correlates of finger opposition movements, allowing follow-up studies and comparisons among different groups of patients.

Multiparametric characterisation of neuronal network activity for in vitro agrochemical neurotoxicity assessment.

The last few decades have seen the marketing of hundreds of new pesticide products with a forecasted expansion of the global agrochemical industry. As several pesticides directly target nervous tissue as their mechanism of toxicity, alternative methods to routine in vivo animal testing, such as the Multi Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to perform sensitive, quick and low cost neuro-toxicological screening. Here, we examined the effects of a training set of eleven active substances known to have neuronal or non-neuronal targets, contained in the most commonly used agrochemicals, on the spontaneous electrical activity of cortical neuronal networks grown on MEAs. A multiparametric characterisation of neuronal network firing and bursting was performed with the aim of investigating how this can contribute to the efficient evaluation of in vitro chemical-induced neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters identified four different groups of chemicals: one wherein only inhibition is observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac); a third in which increases at low chemical concentration are followed by decreases at high concentration, with exception of MISI_B that only decreased (fipronil); a fourth in which no effects are observed (paraquat, glyphosate, imidacloprid, mepiquat). The overall results demonstrated that the multiparametric description of the neuronal networks activity makes MEA-based screening platform an accurate and consistent tool for the evaluation of the toxic potential of chemicals. In particular, among the bursting parameters the MISI_B was the best that correlates with potency and may help to better define chemical toxicity when MFR is affected only at relatively high concentration.

Feasibility Assessment of Micro-Electrode Chip Assay as a Method of Detecting Neurotoxicity in vitro.

Detection and characterization of chemically induced toxic effects in the nervous system represent a challenge for the hazard assessment of chemicals. In vivo, neurotoxicological assessments exploit the fact that the activity of neurons in the central and peripheral nervous system has functional consequences. And so far, no in vitro method for evaluating the neurotoxic hazard has yet been validated and accepted for regulatory purpose. The micro-electrode array (MEA) assay consists of a culture chamber into which an integrated array of micro-electrodes is capable of measuring extracellular electrophysiology (spikes and bursts) from electro-active tissues. A wide variety of electrically excitable biological tissues may be placed onto the chips including primary cultures of nervous system tissue. Recordings from this type of in vitro cultured system are non-invasive, give label free evaluations and provide a higher throughput than conventional electrophysiological techniques. In this paper, 20 substances were tested in a blinded study for their toxicity and dose-response curves were obtained from fetal rat cortical neuronal networks coupled to MEAs. The experimental procedure consisted of evaluating the firing activity (spiking rate) and modification/reduction in response to chemical administration. Native/reference activity, 30 min of activity recording per dilution, plus the recovery points (after 24 h) were recorded. The preliminary data, using a set of chemicals with different mode-of-actions (13 known to be neurotoxic, 2 non-neuroactive and not toxic, and 5 non-neuroactive but toxic) show good predictivity (sensitivity: 0.77; specificity: 0.86; accuracy: 0.85). Thus, the MEA with a neuronal network has the potency to become an effective tool to evaluate the neurotoxicity of substances in vitro.

Application of micro-electrode arrays (MEAs) as an emerging technology for developmental neurotoxicity: evaluation of domoic acid-induced effects in primary cultures of rat cortical neurons.

Due to lack of knowledge only a few industrial chemicals have been identified as developmental neurotoxicants. Current developmental neurotoxicity (DNT) guidelines (OECD and EPA) are based entirely on in vivo studies that are both time consuming and costly. Consequently, there is a high demand to develop alternative in vitro methods for initial screening to prioritize chemicals for further DNT testing. One of the most promising tools for neurotoxicity assessment is the measurement of neuronal electrical activity using micro-electrode arrays (MEAs) that provides a functional and neuronal specific endpoint that until now has been used mainly to detect acute neurotoxicity. Here, electrical activity measurements were evaluated to be a suitable endpoint for the detection of potential developmental neurotoxicants. Initially, primary cortical neurons grown on MEA chips were characterized for different cell markers over time, using immunocytochemistry. Our results show that primary cortical neurons could be a promising in vitro model for DNT testing since some of the most critical neurodevelopment processes such as progenitor cell commitment, proliferation and differentiation of astrocytes and maturation of neurons are present. To evaluate if electrical activity could be a suitable endpoint to detect chemicals with DNT effects, our model was exposed to domoic acid (DomA), a potential developmental neurotoxicant for up to 4 weeks. Long-term exposure to a low concentration (50nM) of DomA increased the basal spontaneous electrical activity as measured by spike and burst rates. Moreover, the effect induced by the GABA(A) receptor antagonist bicuculline was significantly lower in the DomA treated cultures than in the untreated ones. The MEA measurements indicate that chronic exposure to DomA changed the spontaneous electrical activity leading to the possible neuronal mal functioning. The obtained results suggest that the MEAs could be a useful tool to identify compounds with DNT potential.

A novel algorithm for precise identification of spikes in extracellularly recorded neuronal signals.

The spike represents the fundamental bit of information transmitted by the neurons within a network in order to communicate. Then, given the importance of the spike rate as well as the spike time for coding the activity generated at the level of a cell assembly, a relevant issue in extracellular electrophysiology is the correct identification of the spike in multisite recordings from brain areas or neuronal networks. In this paper, we present a novel spike detection algorithm, named Precise Timing Spike Detection (PTSD), aimed at (i) reducing the number of false positives and false negatives, in order to optimize the rate code, and (ii) improving the time precision of the identified spike, in order to optimize the spike timing. The PTSD algorithm considers consecutive portions of the signal and looks for the Relative Maximum/Minimum whose peak-to-peak amplitude is above a defined differential threshold and responds to specific requirements. To validate the algorithm, the presented spike detection has been compared with other methods either commercially available or proposed in the literature by using two benchmarking procedures: (i) visual inspection by a group of experts of a portion of signal recorded from a rat cortical culture and (ii) detection of the spikes generated by a realistic neuronal network model. In both cases our algorithm produced the best performances in terms of efficiency and precision. The ROC curve analysis further proved that the best results are reached by the application of the PTSD.

The complementarity of the technical tools of tissue engineering and the concepts of artificial organs for the design of functional bioartificial tissues.

Although tissue engineering uses powerful biological tools, it still has a weak conceptual foundation, which is restricted at the cell level. The design criteria at the cell level are not directly related with the tissue functions, and consequently, such functions cannot be implemented in bioartificial tissues with the currently used methods. On the contrary, the field of artificial organs focuses on the function of the artificial organs that are treated in the design as integral entities, instead of the optimization of the artificial organ components. The field of artificial organs has already developed and tested methodologies that are based on system concepts and mathematical-computational methods that connect the component properties with the desired global organ function. Such methodologies are needed in tissue engineering for the design of bioartificial tissues with tissue functions. Under the framework of biomedical engineering, artificial organs and tissue engineering do not present competitive approaches, but are rather complementary and should therefore design a common future for the benefit of patients.

The effects of rate and sequence complexity on repetitive finger movements.

We studied the effects of movement rate and sequence complexity on the execution of externally paced finger movements. Simple thumb-index opposition movements (SEQ1), oppositions of thumb to index, medium, ring and little fingers (SEQ2), and oppositions of thumb to index, ring, medium and little fingers (SEQ3) were paced by a metronome at rates that ranged from 0.5 to 5 Hz. At rates higher than 2.5 Hz touch duration, as well as spatial and timing accuracy changed, although with a different pattern, for the sequences. Delayed movements were mostly present at lowest rates in SEQ1; at 0.5 Hz and at frequencies higher than 3.5 Hz in SEQ2; at rates higher than 3.5 Hz in SEQ3. Syncopation occurred at rates higher than 3 Hz but only for SEQ2 and SEQ3 when movements are delayed. Power spectrum analysis of timing error series indicated that SEQ1 performance is influenced by memory-related processes at all movement rates. On the other hand, for the other two sequences, at rates higher than 4 Hz the timing error series exhibit a slight but significant reduction of its long-range correlation characteristics. These findings suggest that different strategies are used for sensorimotor processing when the movement rate and sequence complexity are increased.