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Near-Infrared Light Responsive Multi-Compartmental Hydrogel Particles Synthesized Through Droplets Assembly Induced by Superhydrophobic Surface.
Small. 2014 Jul 24;
Authors: Luo R, Cao Y, Shi P, Chen CH
Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed.
PMID: 25059988 [PubMed - as supplied by publisher]
Neuronal Ensemble Synchrony during Human Focal Seizures.
J Neurosci. 2014 Jul 23;34(30):9927-44
Authors: Truccolo W, Ahmed OJ, Harrison MT, Eskandar EN, Cosgrove GR, Madsen JR, Blum AS, Potter NS, Hochberg LR, Cash SS
Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (?40-60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ?3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50-100 ms level. In addition, transient fine synchrony occurred primarily during the initial ?20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (?80 Hz) gamma-band and during high-frequency oscillations (?130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons.
PMID: 25057195 [PubMed - in process]
Dysfunctional Cortical Inhibition in Adult ADHD: Neural Correlates in Auditory Event-Related Potentials.
J Neurosci Methods. 2014 Jul 14;
Authors: Schubert JK, Gonzalez-Trejo E, Retz W, Rösler M, Corona-Strauss FI, Steidl G, Teuber T, Strauss DJ
In recent times, the relevance of an accurate diagnosis of attention-deficit/ hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.
PMID: 25033725 [PubMed - as supplied by publisher]
Decoding Vigilance with NIRS.
PLoS One. 2014;9(7):e101729
Authors: Bogler C, Mehnert J, Steinbrink J, Haynes JD
Sustained, long-term cognitive workload is associated with variations and decrements in performance. Such fluctuations in vigilance can be a risk factor especially during dangerous attention demanding activities. Functional MRI studies have shown that attentional performance is correlated with BOLD-signals, especially in parietal and prefrontal cortical regions. An interesting question is whether these BOLD-signals could be measured in real-world scenarios, say to warn in a dangerous workplace whenever a subjects' vigilance is low. Because fMRI lacks the mobility needed for such applications, we tested whether the monitoring of vigilance might be possible using Near-Infrared Spectroscopy (NIRS). NIRS is a highly mobile technique that measures hemodynamics in the surface of the brain. We demonstrate that non-invasive NIRS signals correlate with vigilance. These signals carry enough information to decode subjects' reaction times at a single trial level.
PMID: 25032963 [PubMed - as supplied by publisher]
Brain representations for acquiring and recalling visual-motor adaptations.
Neuroimage. 2014 Jul 11;
Authors: Bédard P, Sanes JN
Humans readily learn and remember new motor skills, a process that likely underlies adaptation to changing environments. During adaptation, the brain develops new sensory-motor relationships, and if consolidation occurs, a memory of the adaptation can be retained for extended periods. Considerable evidence exists that multiple brain circuits participate in acquiring new sensory-motor memories, though the networks engaged in recalling these and whether the same brain circuits participate in their formation and recall has less clarity. To address these issues, we assessed brain activation with functional MRI while young healthy adults learned and recalled new sensory-motor skills by adapting to world-view rotations of visual feedback that guided hand movements. We found cerebellar activation related to adaptation rate, likely reflecting changes related to overall adjustments to the visual rotation. A set of parietal and frontal regions, including inferior and superior parietal lobules, premotor area, supplementary motor area and primary somatosensory cortex, exhibited non-linear learning-related activation that peaked in the middle of the adaptation phase. Activation in some of these areas, including the inferior parietal lobule, intra-parietal sulcus and somatosensory cortex, likely reflected actual learning, since the activation correlated with learning after-effects. Lastly, we identified several structures having recall-related activation, including the anterior cingulate and the posterior putamen, since the activation correlated with recall efficacy. These findings demonstrate dynamic aspects of brain activation patterns related to formation and recall of a sensory-motor skill, such that non-overlapping brain regions participate in distinctive behavioral events.
PMID: 25019676 [PubMed - as supplied by publisher]
The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats.
Ther Hypothermia Temp Manag. 2014 Jul 14;
Authors: Bazley FA, Pashai N, Kerr CL, All AH
Local and general hypothermia are used to treat spinal cord injury (SCI), as well as other neurological traumas. While hypothermia is known to provide significant therapeutic benefits due to its neuroprotective nature, it is unclear how the treatment may affect healthy tissues or whether it may cause undesired temperature changes in areas of the body that are not the targets of treatment. We performed 2-hour moderate general hypothermia (32°C core) or local hypothermia (30°C spinal cord) on rats that had received either a moderate contusive SCI or laminectomy (control) while monitoring temperatures at three sites: the core, spinal cord, and cortex. First, we identified that injured rats that received general hypothermia exhibited larger temperature drops at the spinal cord (-3.65°C, 95% confidence intervals [CIs] -3.72, -3.58) and cortex (-3.64°C, CIs -3.73, -3.55) than uninjured rats (spinal cord: -3.17°C, CIs -3.24, -3.10; cortex: -3.26°C, CIs -3.34, -3.17). This was found due to elevated baseline temperatures in the injured group, which could be due to inflammation. Second, both general hypothermia and local hypothermia caused a significant reduction in the cortical temperature (-3.64°C and -1.18°C, respectively), although local hypothermia caused a significantly lower drop in cortical temperature than general hypothermia (p<0.001). Lastly, the rates of rewarming of the cord were not significantly different among the methods or injury groups that were tested; the mean rate of rewarming was 0.13±0.1°C/min. In conclusion, local hypothermia may be more suitable for longer durations of hypothermia treatment for SCI to reduce temperature changes in healthy tissues, including the cortex.
PMID: 25019643 [PubMed - as supplied by publisher]
Dimensionality reduction for the analysis of brain oscillations.
Neuroimage. 2014 Jul 5;
Authors: Haufe S, Dähne S, Nikulin VV
Neuronal oscillations were shown to be associated with perceptual, motor and cognitive brain operations. While complex spatio-temporal dynamics are a hallmark of neuronal oscillations, they also represent a formidable challenge for a proper extraction and quantifications of oscillatory activity with non-invasive recording techniques such as EEG and MEG. In order to facilitate the study of neuronal oscillations we present a general purpose pre-processing approach, which can be applied for a wide range of analyses including but not restricted to inverse modeling and multivariate single-trial classification. The idea is to use dimensionality reduction with spatio-spectral decomposition (SSD) instead of the commonly and almost exclusively used principal component analysis (PCA). The key advantage of SSD lies in selecting components explaining oscillations-related variance instead of just any variance as in the case of PCA. For the validation of SSD pre-processing we performed extensive simulations with different inverse modeling algorithms and signal-to-noise ratios. In all these simulations SSD invariably outperformed PCA often by a large margin. Moreover, using a database of multichannel EEG recordings from 80 subjects we show that pre-processing with SSD significantly increases the performance of single-trial classification of imagined movements, compared to the classification with PCA pre-processing or without any dimensionality reduction. Our simulations and analysis of real EEG experiments show that, while not being supervised, the SSD algorithm is capable of extracting components primarily relating to the signal of interest often using as little as 20 % of the data variance, instead of > 90 % variance as in case of PCA. Given its ease of use, absence of supervision, and capability to efficiently reduce the dimensionality of multivariate EEG/MEG data, we advocate the application of SSD pre-processing for the analysis of spontaneous and induced neuronal oscillations in normal subjects and patients.
PMID: 25003816 [PubMed - as supplied by publisher]
Manipulation of isolated brain nerve terminals by an external magnetic field using D-mannose-coated ?-Fe2O3 nano-sized particles and assessment of their effects on glutamate transport.
Beilstein J Nanotechnol. 2014;5:778-88
Authors: Borisova T, Krisanova N, Bor?sov A, Sivko R, Ostapchenko L, Babic M, Horak D
The manipulation of brain nerve terminals by an external magnetic field promises breakthroughs in nano-neurotechnology. D-Mannose-coated superparamagnetic nanoparticles were synthesized by coprecipitation of Fe(II) and Fe(III) salts followed by oxidation with sodium hypochlorite and addition of D-mannose. Effects of D-mannose-coated superparamagnetic maghemite (?-Fe2O3) nanoparticles on key characteristics of the glutamatergic neurotransmission were analysed. Using radiolabeled L-[(14)C]glutamate, it was shown that D-mannose-coated ?-Fe2O3 nanoparticles did not affect high-affinity Na(+)-dependent uptake, tonic release and the extracellular level of L-[(14)C]glutamate in isolated rat brain nerve terminals (synaptosomes). Also, the membrane potential of synaptosomes and acidification of synaptic vesicles was not changed as a result of the application of D-mannose-coated ?-Fe2O3 nanoparticles. This was demonstrated with the potential-sensitive fluorescent dye rhodamine 6G and the pH-sensitive dye acridine orange. The study also focused on the analysis of the potential use of these nanoparticles for manipulation of nerve terminals by an external magnetic field. It was shown that more than 84.3 ± 5.0% of L-[(14)C]glutamate-loaded synaptosomes (1 mg of protein/mL) incubated for 5 min with D-mannose-coated ?-Fe2O3 nanoparticles (250 µg/mL) moved to an area, in which the magnet (250 mT, gradient 5.5 ?/m) was applied compared to 33.5 ± 3.0% of the control and 48.6 ± 3.0% of samples that were treated with uncoated nanoparticles. Therefore, isolated brain nerve terminals can be easily manipulated by an external magnetic field using D-mannose-coated ?-Fe2O3 nanoparticles, while the key characteristics of glutamatergic neurotransmission are not affected. In other words, functionally active synaptosomes labeled with D-mannose-coated ?-Fe2O3 nanoparticles were obtained.
PMID: 24991515 [PubMed]
Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy.
Biomed Eng Online. 2013;12:120
Authors: Liao LD, Orellana J, Liu YH, Lin YR, Vipin A, Thakor NV, Shen K, Wilder-Smith E
BACKGROUND: Vascular hemodynamics is central to the regulation of neuro-metabolism and plays important roles in peripheral nerves diseases and their prevention. However, at present there are only a few techniques capable of directly measuring peripheral nerve vascular hemodynamics.
METHOD: Here, we investigate the use of dark-field functional photoacoustic microscopy (fPAM) for intrinsic visualizing of the relative hemodynamics of the rat sciatic nerve in response to localized temperature modulation (i.e., cooling and rewarming).
RESULTS AND CONCLUSION: Our main results show that the relative functional total hemoglobin concentration (HbT) is more significantly correlated with localized temperature changes than the hemoglobin oxygen saturation (SO2) changes in the sciatic nerve. Our study also indicates that the relative HbT changes are better markers of neuronal activation than SO2 during nerve temperature changes. Our results show that fPAM is a promising candidate for in vivo imaging of peripheral nerve hemodynamics without the use of contrast agents. Additionally, this technique may shed light on the neuroprotective effect of hypothermia on peripheral nerves by visualizing their intrinsic hemodynamics.
PMID: 24245952 [PubMed - indexed for MEDLINE]
Discriminative Analysis of Brain Functional Connectivity Patterns for Mental Fatigue Classification.
Ann Biomed Eng. 2014 Jun 25;
Authors: Sun Y, Lim J, Meng J, Kwok K, Thakor N, Bezerianos A
Mental fatigue is a commonly experienced state that can be induced by placing heavy demands on cognitive systems. This often leads to lowered productivity and increased safety risks. In this study, we developed a functional-connectivity based mental fatigue monitoring method. Twenty-six subjects underwent a 20-min mentally demanding test of sustained attention with high-resolution EEG monitoring. Functional connectivity patterns were obtained on the cortical surface via source localization of cortical activities in the first and last 5-min quartiles of the experiment. Multivariate pattern analysis was then adopted to extract the highly discriminative functional connectivity information. The algorithm used in the present study demonstrated an overall accuracy of 81.5% (p < 0.0001) for fatigue classification through leave-one-out cross validation. Moreover, we found that the most discriminative connectivity features were located in or across middle frontal gyrus and several motor areas, in agreement with the important role that these cortical regions play in the maintenance of sustained attention. This work therefore demonstrates the feasibility of a functional-connectivity-based mental fatigue assessment method, opening up a new avenue for modeling natural brain dynamics under different mental states. Our method has potential applications in several domains, including traffic and industrial safety.
PMID: 24962984 [PubMed - as supplied by publisher]
The Analytic Bilinear Discrimination of Single-Trial EEG Signals in Rapid Image Triage.
PLoS One. 2014;9(6):e100097
Authors: Yu K, Ai-Nashash H, Thakor N, Li X
The linear discriminant analysis (LDA) method is a classical and commonly utilized technique for dimensionality reduction and classification in brain-computer interface (BCI) systems. Being a first-order discriminator, LDA is usually preceded by the feature extraction of electroencephalogram (EEG) signals, as multi-density EEG data are of second order. In this study, an analytic bilinear classification method which inherits and extends LDA is proposed. This method considers 2-dimentional EEG signals as the feature input and performs classification using the optimized complex-valued bilinear projections. Without being transformed into frequency domain, the complex-valued bilinear projections essentially spatially and temporally modulate the phases and magnitudes of slow event-related potentials (ERPs) elicited by distinct brain states in the sense that they become more separable. The results show that the proposed method has demonstrated its discriminating capability in the development of a rapid image triage (RIT) system, which is a challenging variant of BCIs due to the fast presentation speed and consequently overlapping of ERPs.
PMID: 24933017 [PubMed - as supplied by publisher]
Chronic Treatment with Mood-Stabilizers Attenuates Abnormal Hyperlocomotion of GluA1-Subunit Deficient Mice.
PLoS One. 2014;9(6):e100188
Authors: Maksimovic M, Vekovischeva OY, Aitta-Aho T, Korpi ER
Abnormal excitatory glutamate neurotransmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1-/- mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1-/- mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1-/- mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but ran similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1-/- mouse line can be utilized in screening for new therapeutics.
PMID: 24932798 [PubMed - as supplied by publisher]
Single cell kinase signaling assay using pinched flow coupled droplet microfluidics.
Biomicrofluidics. 2014 May;8(3):034104
Authors: Ramji R, Wang M, Bhagat AA, Tan Shao Weng D, Thakor NV, Teck Lim C, Chen CH
Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5?cm). In this study, we developed a short pinched flow channel (5?mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12?h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib.
PMID: 24926389 [PubMed - as supplied by publisher]
Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.
J Neural Eng. 2014 Jun 12;11(4):046007
Authors: Perge JA, Zhang S, Malik WQ, Homer ML, Cash S, Friehs G, Eskandar EN, Donoghue JP, Hochberg LR
Objective. Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Significance. Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041.).
PMID: 24921388 [PubMed - as supplied by publisher]
A brain-computer interface for single-trial detection of gait initiation from movement related cortical potentials.
Clin Neurophysiol. 2014 May 20;
Authors: Jiang N, Gizzi L, Mrachacz-Kersting N, Dremstrup K, Farina D
OBJECTIVE: Applications of brain-computer interfacing (BCI) in neurorehabilitation have received increasing attention. The intention to perform a motor task can be detected from scalp EEG and used to control rehabilitation devices, resulting in a patient-driven rehabilitation paradigm. In this study, we present and validate a BCI system for detection of gait initiation using movement related cortical potentials (MRCP).
METHODS: The templates of MRCP were extracted from 9-channel scalp EEG during gait initiation in 9 healthy subjects. Independent component analysis (ICA) was used to remove artifacts, and the Laplacian spatial filter was applied to enhance the signal-to-noise ratio of MRCP. Following these pre-processing steps, a matched filter was used to perform single-trial detection of gait initiation.
RESULTS: ICA preprocessing was shown to significantly improve the detection performance. With ICA preprocessing, across all subjects, the true positive rate (TPR) of the detection was 76.9±8.97%, and the false positive rate was 2.93±1.09 per minute.
CONCLUSION: The results demonstrate the feasibility of detecting the intention of gait initiation from EEG signals, on a single trial basis.
SIGNIFICANCE: The results are important for the development of new gait rehabilitation strategies, either for recovery/replacement of function or for neuromodulation.
PMID: 24910150 [PubMed - as supplied by publisher]
Motor modules of human locomotion: influence of EMG averaging, concatenation, and number of step cycles.
Front Hum Neurosci. 2014;8:335
Authors: Oliveira AS, Gizzi L, Farina D, Kersting UG
Locomotion can be investigated by factorization of electromyographic (EMG) signals, e.g., with non-negative matrix factorization (NMF). This approach is a convenient concise representation of muscle activities as distributed in motor modules, activated in specific gait phases. For applying NMF, the EMG signals are analyzed either as single trials, or as averaged EMG, or as concatenated EMG (data structure). The aim of this study is to investigate the influence of the data structure on the extracted motor modules. Twelve healthy men walked at their preferred speed on a treadmill while surface EMG signals were recorded for 60s from 10 lower limb muscles. Motor modules representing relative weightings of synergistic muscle activations were extracted by NMF from 40 step cycles separately (EMGSNG), from averaging 2, 3, 5, 10, 20, and 40 consecutive cycles (EMGAVR), and from the concatenation of the same sets of consecutive cycles (EMGCNC). Five motor modules were sufficient to reconstruct the original EMG datasets (reconstruction quality >90%), regardless of the type of data structure used. However, EMGCNC was associated with a slightly reduced reconstruction quality with respect to EMGAVR. Most motor modules were similar when extracted from different data structures (similarity >0.85). However, the quality of the reconstructed 40-step EMGCNC datasets when using the muscle weightings from EMGAVR was low (reconstruction quality ~40%). On the other hand, the use of weightings from EMGCNC for reconstructing this long period of locomotion provided higher quality, especially using 20 concatenated steps (reconstruction quality ~80%). Although EMGSNG and EMGAVR showed a higher reconstruction quality for short signal intervals, these data structures did not account for step-to-step variability. The results of this study provide practical guidelines on the methodological aspects of synergistic muscle activation extraction from EMG during locomotion.
PMID: 24904375 [PubMed]
Stereovision and augmented reality for closed-loop control of grasping in hand prostheses.
J Neural Eng. 2014 Jun 3;11(4):046001
Authors: Markovic M, Dosen S, Cipriani C, Popovic D, Farina D
Objective. Technologically advanced assistive devices are nowadays available to restore grasping, but effective and effortless control integrating both feed-forward (commands) and feedback (sensory information) is still missing. The goal of this work was to develop a user friendly interface for the semi-automatic and closed-loop control of grasping and to test its feasibility. Approach. We developed a controller based on stereovision to automatically select grasp type and size and augmented reality (AR) to provide artificial proprioceptive feedback. The system was experimentally tested in healthy subjects using a dexterous hand prosthesis to grasp a set of daily objects. The subjects wore AR glasses with an integrated stereo-camera pair, and triggered the system via a simple myoelectric interface. Main results. The results demonstrated that the subjects got easily acquainted with the semi-autonomous control. The stereovision grasp decoder successfully estimated the grasp type and size in realistic, cluttered environments. When allowed (forced) to correct the automatic system decisions, the subjects successfully utilized the AR feedback and achieved close to ideal system performance. Significance. The new method implements a high level, low effort control of complex functions in addition to the low level closed-loop control. The latter is achieved by providing rich visual feedback, which is integrated into the real life environment. The proposed system is an effective interface applicable with small alterations for many advanced prosthetic and orthotic/therapeutic rehabilitation devices.
PMID: 24891493 [PubMed - as supplied by publisher]
Towards User-Friendly Spelling with an Auditory Brain-Computer Interface: The CharStreamer Paradigm.
PLoS One. 2014;9(6):e98322
Authors: Höhne J, Tangermann M
Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI) aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: "CharStreamer". The speller can be used with an instruction as simple as "please attend to what you want to spell". The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions) is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n?=?10) of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences.
PMID: 24886978 [PubMed - as supplied by publisher]
The effective neural drive to muscles is the common synaptic input to motor neurons.
J Physiol. 2014 May 23;
Authors: Farina D, Negro F, Dideriksen JL
We analyzed the transformation of synaptic input to the pool of motor neurons into the neural drive to the muscle. The aim was to explain the relations between common oscillatory signals sent to motor neurons and the effective component of the neural signal sent to muscles as output of the spinal cord circuitries. The approach is based on theoretical derivations, computer simulations, and experiments. It is shown theoretically that for frequencies smaller than the average discharge rates of the motor neurons, the pool of motor neurons determines a pure amplification of the frequency components common to all motor neurons, so that the common input is transmitted almost undistorted and the non-common components are strongly attenuated. The effective neural drive to the muscle thus mirrors the common synaptic input to motor neurons. The simulations with three models of motor neuron confirmed the theoretical results by showing that the coherence function between common input components and the neural drive to the muscle tends to one when increasing the number of active motor neurons. This result, which was relatively insensitive to the type of model used, was also supported experimentally by observing that, in the low-pass signal bandwidth, the peak in coherence between groups of motor units of the abductor digiti minimi muscle of 5 healthy subjects tended to one when increasing the number of motor units. These results have implications for our understanding of the neural control of muscles as well as for methods used for estimating the strength of common input to populations of motor neurons. This article is protected by copyright. All rights reserved.
PMID: 24860172 [PubMed - as supplied by publisher]
The Right Dorsal Habenula Limits Attraction to an Odor in Zebrafish.
Curr Biol. 2014 May 21;
Authors: Krishnan S, Mathuru AS, Kibat C, Rahman M, Lupton CE, Stewart J, Claridge-Chang A, Yen SC, Jesuthasan S
BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays.
RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance.
CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.
PMID: 24856207 [PubMed - as supplied by publisher]
Near-infrared light triggerable deformation-free polysaccharide double network hydrogels.
Chem Commun (Camb). 2014 May 22;
Authors: Luo RC, Lim ZH, Li W, Shi P, Chen CH
To prepare a hydrogel with robust mechanical properties and programmable remotely-controlled releasing ability, we synthesized an agarose/alginate double network hydrogel incorporating polypyrrole (PPy) nanoparticles as a near-infrared (NIR) laser responsive releasing system. This hydrogel exhibited pulsatile releasing behaviours according to the laser switching while maintaining its morphology and mechanical strength.
PMID: 24849317 [PubMed - as supplied by publisher]
Amyloid precursor protein at node of Ranvier modulates nodal formation.
Cell Adh Migr. 2014 Apr 11;8(4)
Authors: Xu DE, Zhang WM, Yang ZZ, Zhu HM, Yan K, Li S, Bagnard D, Dawe GS, Ma QH, Xiao ZC
Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.
PMID: 24846210 [PubMed - as supplied by publisher]
EEG predictors of covert vigilant attention.
J Neural Eng. 2014 May 19;11(3):035009
Authors: Martel A, Dähne S, Blankertz B
Objective. The present study addressed the question whether neurophysiological signals exhibit characteristic modulations preceding a miss in a covert vigilant attention task which mimics a natural environment in which critical stimuli may appear in the periphery of the visual field. Approach. Subjective, behavioural and encephalographic (EEG) data of 12 participants performing a modified Mackworth Clock task were obtained and analysed offline. The stimulus consisted of a pointer performing regular ticks in a clockwise sequence across 42 dots arranged in a circle. Participants were requested to covertly attend to the pointer and press a response button as quickly as possible in the event of a jump, a rare and random event. Main results. Significant increases in response latencies and decreases in the detection rates were found as a function of time-on-task, a characteristic effect of sustained attention tasks known as the vigilance decrement. Subjective sleepiness showed a significant increase over the duration of the experiment. Increased activity in the ?-frequency range (8-14 Hz) was observed emerging and gradually accumulating 10 s before a missed target. Additionally, a significant gradual attenuation of the P3 event-related component was found to antecede misses by 5 s. Significance. The results corroborate recent findings that behavioural errors are presaged by specific neurophysiological activity and demonstrate that lapses of attention can be predicted in a covert setting up to 10 s in advance reinforcing the prospective use of brain-computer interface (BCI) technology for the detection of waning vigilance in real-world scenarios. Combining these findings with real-time single-trial analysis from BCI may pave the way for cognitive states monitoring systems able to determine the current, and predict the near-future development of the brain's attentional processes.
PMID: 24835495 [PubMed - as supplied by publisher]
Disrupted Functional Brain Connectivity and Its Association to Structural Connectivity in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.
PLoS One. 2014;9(5):e96505
Authors: Sun Y, Yin Q, Fang R, Yan X, Wang Y, Bezerianos A, Tang H, Miao F, Sun J
Although anomalies in the topological architecture of whole-brain connectivity have been found to be associated with Alzheimer's disease (AD), our understanding about the progression of AD in a functional connectivity (FC) perspective is still rudimentary and few study has explored the function-structure relations in brain networks of AD patients. By using resting-state functional MRI (fMRI), this study firstly investigated organizational alternations in FC networks in 12 AD patients, 15 amnestic mild cognitive impairment (aMCI) patients, and 14 age-matched healthy aging subjects and found that all three groups exhibit economical small-world network properties. Nonetheless, we found a decline of the optimal architecture in the progression of AD, represented by a more localized modular organization with less efficient local information transfer. Our results also show that aMCI forms a boundary between normal aging and AD and represents a functional continuum between healthy aging and the earliest signs of dementia. Moreover, we revealed a dissociated relationship between the overall FC and structural connectivity (SC) in AD patients. In this study, diffusion tensor imaging tractography was used to map the structural network of the same individuals. The decreased FC-SC coupling may be indicative of more stringent and less dynamic brain function in AD patients. Our findings provided insightful implications for understanding the pathophysiological mechanisms of brain dysfunctions in aMCI and AD patients and demonstrated that functional disorders can be characterized by multimodal neuroimaging-based metrics.
PMID: 24806295 [PubMed - as supplied by publisher]
Safe Use of Repetitive Transcranial Magnetic Stimulation in Patients With Implanted Vagus Nerve Stimulators.
Brain Stimul. 2014 Apr 12;
Authors: Philip NS, Carpenter SL, Carpenter LL
Vagus nerve stimulation (VNS) and repetitive transcranial stimulation (rTMS) devices are FDA cleared for therapeutic use in treatment resistant depression. Since VNS systems have ferromagnetic components and large-scale safety testing has not been done, the implanted VNS device is considered a contraindication for rTMS therapy. This contraindication should not be considered absolute, as VNS components typically lie outside the electromagnetic field generated by an rTMS treatment coil. We solicited information from clinicians at several academic medical centers through an informal survey about their use of rTMS for depressed patients with implanted VNS systems, and reviewed relevant safety issues with one rTMS device manufacturer. rTMS clinical practices may use special consent procedures and take additional precautions to enhance safety in these situations. Specific recommendations are provided for minimizing risks (heating or movement of VNS components and unintended change in VNS stimulation parameters) when delivering rTMS to patients with implanted VNS systems.
PMID: 24794163 [PubMed - as supplied by publisher]
Neurotechnology: A New Approach for Treating Brain Disorders.
R I Med J (2013). 2014;96(3):18-21
Authors: Robson JA, Davenport RJ
Advances in neuroscience, engineering and computer technologies are creating opportunities to connect the brain directly to devices to treat a variety of disorders, both neurological and psychiatric. They are opening a new field of neuroscience called "neurotechnology." This article reviews efforts in this area that are ongoing at Brown University and the hospitals affiliated with Brown's Alpert Medical School. Two general approaches are being used. One uses advanced electrodes to "sense" the activity of many individual neurons in the cerebral cortex and then use that activity for therapeutic purposes. The other uses various types of devices to stimulate specific networks in the brain in order to restore normal function and alleviate symptoms. [Full text available at http://rimed.org/rimedicaljournal-2014-05.asp, free with no login].
PMID: 24791262 [PubMed - as supplied by publisher]
Locked in, but not out?
Neurology. 2014 Apr 30;
Authors: Hochberg LR, Cudkowicz ME
The most devastating aspect of amyotrophic lateral sclerosis (ALS) may not be the loss of mobility or spontaneous respiration but the inability to communicate. For people with ALS who elect mechanical ventilation, the inexorable disease progression can lead to an incomplete locked-in syndrome (LIS)(1,2) and then to a total LIS where neither eye movements nor any other efferent capacity remains. The moment that occurs, consciousness undoubtedly persists, but for an unknown period of time. In some cases, years later, family members maintain that their loved one is communicating by changing pupil size or pulse rate, or just a look in the eye. The dispassionate physician remains uncertain, perhaps believing that consciousness requires not just an internal dialogue but also observing the results of thoughts or actions. Others may quietly hope that consciousness cannot survive extended periods of immobility, unannounced and unmitigated discomfort, and complete disconnection.
PMID: 24789868 [PubMed - as supplied by publisher]
Indestructible plastic: the neuroscience of the new aging brain.
Front Hum Neurosci. 2014;8:219
Authors: Holman C, de Villers-Sidani E
In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.
PMID: 24782746 [PubMed - as supplied by publisher]
Finding brain oscillations with power dependencies in neuroimaging data.
Neuroimage. 2014 Apr 7;
Authors: Dähne S, Nikulin VV, Ramírez D, Schreier PJ, Müller KR, Haufe S
Phase synchronization among neuronal oscillations within the same frequency band has been hypothesized to be a major mechanism for communication between different brain areas. On the other hand, cross-frequency communications are more flexible allowing interactions between oscillations with different frequencies. Among such cross-frequency interactions amplitude-to-amplitude interactions are of a special interest as they show how the strength of spatial synchronization in different neuronal populations relates to each other during a given task. While, previously, amplitude-to-amplitude correlations were studied primarily on the sensor level, we present a source separation approach using spatial filters which maximize the correlation between the envelopes of brain oscillations recorded with electro-/magnetencephalography (EEG/MEG) or intracranial multichannel recordings. Our approach, which is called canonical source power correlation analysis (cSPoC), is thereby capable of extracting genuine brain oscillations solely based on their assumed coupling behavior even when the signal-to-noise ratio of the signals is low. In addition to using cSPoC for the analysis of cross-frequency interactions in the same subject, we show that it can also be utilized for studying amplitude dynamics of neuronal oscillations across subjects. We assess the performance of cSPoC in simulations as well as in three distinctively different analysis scenarios of real EEG data, each involving several subjects. In the simulations, cSPoC outperforms unsupervised state-of-art approaches. In the analysis of real EEG recordings, we demonstrate excellent unsupervised discovery of meaningful power-to-power couplings, within as well as across subjects and frequency bands.
PMID: 24721331 [PubMed - as supplied by publisher]
Manipulating measurement scales in medical statistical analysis and data mining: A review of methodologies.
J Res Med Sci. 2014 Jan;19(1):47-56
Authors: Marateb HR, Mansourian M, Adibi P, Farina D
BACKGROUND: selecting the correct statistical test and data mining method depends highly on the measurement scale of data, type of variables, and purpose of the analysis. Different measurement scales are studied in details and statistical comparison, modeling, and data mining methods are studied based upon using several medical examples. We have presented two ordinal-variables clustering examples, as more challenging variable in analysis, using Wisconsin Breast Cancer Data (WBCD).
ORDINAL-TO-INTERVAL SCALE CONVERSION EXAMPLE: a breast cancer database of nine 10-level ordinal variables for 683 patients was analyzed by two ordinal-scale clustering methods. The performance of the clustering methods was assessed by comparison with the gold standard groups of malignant and benign cases that had been identified by clinical tests.
RESULTS: the sensitivity and accuracy of the two clustering methods were 98% and 96%, respectively. Their specificity was comparable.
CONCLUSION: by using appropriate clustering algorithm based on the measurement scale of the variables in the study, high performance is granted. Moreover, descriptive and inferential statistics in addition to modeling approach must be selected based on the scale of the variables.
PMID: 24672565 [PubMed - as supplied by publisher]