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Slipping during side-step cutting: Anticipatory effects and familiarization.
Hum Mov Sci. 2014 Feb 21;
Authors: Oliveira AS, Silva PB, Lund ME, Farina D, Kersting UG
The aim of the present study was to verify whether the expectation of perturbations while performing side-step cutting manoeuvres influences lower limb EMG activity, heel kinematics and ground reaction forces. Eighteen healthy men performed two sets of 90° side-step cutting manoeuvres. In the first set, 10 unperturbed trials (Base) were performed while stepping over a moveable force platform. In the second set, subjects were informed about the random possibility of perturbations to balance throughout 32 trials, of which eight were perturbed (Pert, 10cm translation triggered at initial contact), and the others were "catch" trials (Catch). Center of mass velocity (CoMVEL), heel acceleration (HAC), ground reaction forces (GRF) and surface electromyography (EMG) from lower limb and trunk muscles were recorded for each trial. Surface EMG was analyzed prior to initial contact (PRE), during load acceptance (LA) and propulsion (PRP) periods of the stance phase. In addition, hamstrings-quadriceps co-contraction ratios (CCR) were calculated for these time-windows. The results showed no changes in CoMVEL, HAC, peak GRF and surface EMG PRE among conditions. However, during LA, there were increases in tibialis anterior EMG (30-50%) concomitant to reduced EMG for quadriceps muscles, gluteus and rectus abdominis for Catch and Pert conditions (15-40%). In addition, quadriceps EMG was still reduced during PRP (p<.05). Consequently, CCR was greater for Catch and Pert in comparison to Base (p<.05). These results suggest that there is modulation of muscle activity towards anticipating potential instability in the lower limb joints and assure safety to complete the task.
PMID: 24565168 [PubMed - as supplied by publisher]
Inducible and titratable silencing of Caenorhabditis elegans neurons in vivo with histamine-gated chloride channels.
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2770-5
Authors: Pokala N, Liu Q, Gordus A, Bargmann CI
Recent progress in neuroscience has been facilitated by tools for neuronal activation and inactivation that are orthogonal to endogenous signaling systems. We describe here a chemical-genetic approach for inducible silencing of Caenorhabditis elegans neurons in intact animals, using the histamine-gated chloride channel HisCl1 from Drosophila and exogenous histamine. Administering histamine to freely moving C. elegans that express HisCl1 transgenes in neurons leads to rapid and potent inhibition of neural activity within minutes, as assessed by behavior, functional calcium imaging, and electrophysiology of neurons expressing HisCl1. C. elegans does not use histamine as an endogenous neurotransmitter, and exogenous histamine has little apparent effect on wild-type C. elegans behavior. HisCl1-histamine silencing of sensory neurons, interneurons, and motor neurons leads to behavioral effects matching their known functions. In addition, the HisCl1-histamine system can be used to titrate the level of neural activity, revealing quantitative relationships between neural activity and behavioral output. We use these methods to dissect escape circuits, define interneurons that regulate locomotion speed (AVA, AIB) and escape-related omega turns (AIB), and demonstrate graded control of reversal length by AVA interneurons and DA/VA motor neurons. The histamine-HisCl1 system is effective, robust, compatible with standard behavioral assays, and easily combined with optogenetic tools, properties that should make it a useful addition to C. elegans neurotechnology.
PMID: 24550306 [PubMed - in process]
Exploiting the self-similarity in ERP images by nonlocal means for single-trial denoising.
IEEE Trans Neural Syst Rehabil Eng. 2013 Jul;21(4):576-83
Authors: Strauss DJ, Teuber T, Steidl G, Corona-Strauss FI
Event related potentials (ERPs) represent a noninvasive and widely available means to analyze neural correlates of sensory and cognitive processing. Recent developments in neural and cognitive engineering proposed completely new application fields of this well-established measurement technique when using an advanced single-trial processing. We have recently shown that 2-D diffusion filtering methods from image processing can be used for the denoising of ERP single-trials in matrix representations, also called ERP images. In contrast to conventional 1-D transient ERP denoising techniques, the 2-D restoration of ERP images allows for an integration of regularities over multiple stimulations into the denoising process. Advanced anisotropic image restoration methods may require directional information for the ERP denoising process. This is especially true if there is a lack of a priori knowledge about possible traces in ERP images. However due to the use of event related experimental paradigms, ERP images are characterized by a high degree of self-similarity over the individual trials. In this paper, we propose the simple and easy to apply nonlocal means method for ERP image denoising in order to exploit this self-similarity rather than focusing on the edge-based extraction of directional information. Using measured and simulated ERP data, we compare our method to conventional approaches in ERP denoising. It is concluded that the self-similarity in ERP images can be exploited for single-trial ERP denoising by the proposed approach. This method might be promising for a variety of evoked and event-related potential applications, including nonstationary paradigms such as changing exogeneous stimulus characteristics or endogenous states during the experiment. As presented, the proposed approach is for the a posteriori denoising of single-trial sequences.
PMID: 23060344 [PubMed - indexed for MEDLINE]
Time to address the problems at the neural interface.
J Neural Eng. 2014 Feb 6;11(2):020201
Authors: Durand DM, Ghovanloo M, Krames E
Neural engineers have made significant, if not remarkable, progress in interfacing with the nervous system in the last ten years. In particular, neuromodulation of the brain has generated significant therapeutic benefits [1-5]. EEG electrodes can be used to communicate with patients with locked-in syndrome . In the central nervous system (CNS), electrode arrays placed directly over or within the cortex can record neural signals related to the intent of the subject or patient [7, 8]. A similar technology has allowed paralyzed patients to control an otherwise normal skeletal system with brain signals [9, 10]. This technology has significant potential to restore function in these and other patients with neural disorders such as stroke . Although there are several multichannel arrays described in the literature, the workhorse for these cortical interfaces has been the Utah array . This 100-channel electrode array has been used in most studies on animals and humans since the 1990s and is commercially available. This array and other similar microelectrode arrays can record neural signals with high quality (high signal-to-noise ratio), but these signals fade and disappear after a few months and therefore the current technology is not reliable for extended periods of time. Therefore, despite these major advances in communicating with the brain, clinical translation cannot be implemented. The reasons for this failure are not known but clearly involve the interface between the electrode and the neural tissue. The Defense Advanced Research Project Agency (DARPA) as well as other federal funding agencies such as the National Science Foundation (NSF) and the National Institutes of Health have provided significant financial support to investigate this problem without much success. A recent funding program from DARPA was designed to establish the failure modes in order to generate a reliable neural interface technology and again was unsuccessful at producing a robust interface with the CNS. In 2013, two symposia were held independently to discuss this problem: one was held at the International Neuromodulation Society's 11th World Congress in Berlin and supported by the International Neuromodulation Society(1) and the other at the 6th International Neural Engineering conference in San Diego(2) and was supported by the NSF. Clearly, the neuromodulation and the neural engineering communities are keen to solve this problem. Experts from the field were assembled to discuss the problems and potential solutions. Although many important points were raised, few emerged as key issues. (1) The ability to access remotely and reliably internal neural signals . Although some of the technological problems have already been solved, this ability to access neural signals is still a significant problem since reliable and robust transcutaneous telemetry systems with large numbers of signals, each with wide bandwidth, are not readily available to researchers. (2) A translation strategy taking basic research to the clinic . The lack of understanding of the biological response to implanted constructs and the inability to monitor the sites and match the mechanical properties of the probe to the neural tissue properties continue to be an unsolved problem. In addition, the low levels of collaboration among neuroscientists, clinicians, patients and other stakeholders throughout different phases of research and development were considered to be significant impediments to progress. (3) Fundamental tools development procedures for neural interfacing . There are many laboratories testing various devices with different sets of criteria, but there is no consensus on the failure modes. The reliability, robustness of metrics and testing standards for such devices have not been established, either in academia or in industry. To start addressing this problem, the FDA has established a laboratory to test the reliability of some neural devices. Although the discussion was mostly centered on interfacing with the CNS, it has recently become clear that the peripheral nervous system (PNS) could be an important target for interfacing, perhaps even more accessible for interfacing than the CNS. A recent initiative called Bioelectronic Medicines(3) is a step in that direction. A recent summit held in New York was organized to investigate novel and disruptive neural technologies to interface specifically with the PNS in order to restore health and biological function to organs. With significant interest in neurotechnology for neural interfacing (see footnotes 1, 2 and 3) and uncovering new ways to treat, prevent and cure brain disorders (President Obama's brain initiative(4)), it seems clear that the problems at the interface will not remain unsolved for long. Finding solutions to the problem at the neural interface for interacting with the nervous system (PNS and CNS) is crucial for understanding and restoring brain function. This would in turn have a significant impact on health care and quality of life for patients with neural disorders. References  Follett K A et al 2010 Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease New Engl. J. Med. 362 2077-91  Holtzheimer P E et al 2012 Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression Arch. Gen. Psychiatry 69 150  Carron R, Chabardes S and Hammond C 2012 Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts NeuroChirurgie 58 209-17  Vidailhet M et al 2005 Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia New Engl. J. Med. 352 459-67  Theodore W H and Fisher R S 2004 Brain stimulation for epilepsy Lancet Neurol. 3 111-8  Kübler A, Kotchoubey B, Kaiser J, Wolpaw J R and Birbaumer N 2001 Brain-computer communication: unlocking the locked Psychol. Bull. 127 358-75  Schalk G, Miller K J, Anderson N R, Wilson J A, Smyth M D, Ojemann J G, Moran D W, Wolpaw J R and Leuthardt E C 2008 Two-dimensional movement control using electrocorticographic signals in humans J. Neural Eng. 5 75  Serruya M D, Hatsopoulos N G, Paninski L, Fellows M R and Donoghue J P 2002 Brain-machine interface: instant neural control of a movement signal Nature 416 141-2  Hochberg L R, Serruya M D, Friehs G M, Mukand J A, Saleh M, Caplan A H, Branner A, Chen D, Penn R D and Donoghue J P 2006 Neuronal ensemble control of prosthetic devices by a human with tetraplegia Nature 442 164-71  Collinger J L et al 2013 High-performance neuroprosthetic control by an individual with tetraplegia Lancet 381 557-64  Leuthardt E C, Schalk G, Wolpaw J R, Ojemann J G and Moran D W 2004 A brain-computer interface using electrocorticographic signals in humans J. Neural Eng. 1 63  Maynard E M, Nordhausen C T and Normann R A 1997 The Utah intracortical electrode array: a recording structure for potential brain-computer interfaces Electroencephalogr. Clin. Neurophysiol. 102 228-39 (1) www.neuromodulation.com/8-june-2013 (2) http://neuro.embs.org/wp-content/uploads/sites/2/2013/05/SymposiumAdvert1.pdf (3) www.gsk.com/explore-gsk/how-we-do-r-and-d/bioelectronics.html (4) www.whitehouse.gov/share/brain-initiative.
PMID: 24503546 [PubMed - as supplied by publisher]
Reduced task-induced variations in the distribution of activity across back muscle regions in individuals with low back pain.
Pain. 2014 Feb 3;
Authors: Falla D, Gizzi L, Tschapek M, Erlenwein J, Petzke F
This study investigated change in the distribution of lumbar erector spinae muscle activity and pressure pain sensitivity across the low back in individuals with low back pain (LBP) and healthy controls. Surface electromyographic (EMG) signals were recorded from multiple locations over the lumbar erector spinae muscle with a 13×5 grid of electrodes from 19 people with chronic non-specific LBP and 17 control subjects as they performed a repetitive lifting task. The EMG root mean square (RMS) was computed for each location of the grid to form a map of the EMG amplitude distribution. Pressure pain thresholds (PPT) were recorded before and after the lifting task over a similar area of the back. For the control subjects, the EMG RMS progressively increased more in the caudal region of the lumbar erector spinae during the repetitive task resulting in a shift in the distribution of muscle activity. In contrast, the distribution of muscle activity remained unaltered in the LBP group despite an overall increase in EMG amplitude. PPT was lower in the LBP group after completion of the repetitive task compared to baseline (average across all locations: pre: 268.0±165.9kPa; post: 242.0±166.7kPa) whereas no change in PPT over time was observed for the control group (320.1±162.1kPa; post: 322.0±179.5kPa). The results demonstrate that LBP alters the normal adaptation of lumbar erector spinae muscle activity to exercise which occurs in the presence of exercise-induced hyperalgesia. Reduced variability of muscle activity may have important implications for the provocation and recurrence of LBP due to repetitive tasks.
PMID: 24502841 [PubMed - as supplied by publisher]
A hybrid intelligent system for diagnosing microalbuminuria in type 2 diabetes patients without having to measure urinary albumin.
Comput Biol Med. 2014 Feb;45:34-42
Authors: Marateb HR, Mansourian M, Faghihimani E, Amini M, Farina D
Microalbuminuria (MA) is an independent predictor of cardiovascular and renal disease, development of overt nephropathy, and cardiovascular mortality in patients with type 2 diabetes. Detecting MA is an important screening tool to identify people with high risk of cardiovascular and kidney disease. The gold standard to detect MA is measuring 24-h urine albumin excretion. A new method for MA diagnosis is presented in this manuscript which uses clinical parameters usually monitored in type 2 diabetic patients without the need of an additional measurement of urinary albumin. We designed an expert-based fuzzy MA classifier in which rule induction was performed by particle swarm optimization. A variety of classifiers was tested. Additionally, multiple logistic regression was used for statistical feature extraction. The significant features were age, diabetic duration, body mass index and HbA1C (the average level of blood sugar over the previous 3 months, which is routinely checked every 3 months for diabetic patients). The resulting classifier was tested on a sample size of 200 patients with type 2 diabetes in a cross-sectional study. The performance of the proposed classifier was assessed using (repeated) holdout and 10-fold cross-validation. The minimum sensitivity, specificity, precision and accuracy of the proposed fuzzy classifier system with feature extraction were 95%, 85%, 84% and 92%, respectively. The proposed hybrid intelligent system outperformed other tested classifiers and showed "almost perfect agreement" with the gold standard. This algorithm is a promising new tool for screening MA in type-2 diabetic patients.
PMID: 24480161 [PubMed - in process]
Can retinal ganglion cell dipoles seed iso-orientation domains in the visual cortex?
PLoS One. 2014;9(1):e86139
Authors: Schottdorf M, Eglen SJ, Wolf F, Keil W
It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglion cells (RGCs). The typical spacing between adjacent cortical orientation columns preferring the same orientation then arises via Moiré-Interference between hexagonal ON/OFF RGC mosaics. While this Moiré-Interference critically depends on long-range hexagonal order within the RGC mosaics, a recent statistical analysis of RGC receptive field positions found no evidence for such long-range positional order. Hexagonal order may be only one of several ways to obtain spatially repetitive OPMs in the statistical connectivity model. Here, we investigate a more general requirement on the spatial structure of RGC mosaics that can seed the emergence of spatially repetitive cortical OPMs, namely that angular correlations between so-called RGC dipoles exhibit a spatial structure similar to that of OPM autocorrelation functions. Both in cat beta cell mosaics as well as primate parasol receptive field mosaics we find that RGC dipole angles are spatially uncorrelated. To help assess the level of these correlations, we introduce a novel point process that generates mosaics with realistic nearest neighbor statistics and a tunable degree of spatial correlations of dipole angles. Using this process, we show that given the size of available data sets, the presence of even weak angular correlations in the data is very unlikely. We conclude that the layout of ON/OFF ganglion cell mosaics lacks the spatial structure necessary to seed iso-orientation domains in the primary visual cortex.
PMID: 24475081 [PubMed - in process]
Functional cortical connectivity analysis of mental fatigue unmasks hemispheric asymmetry and changes in small-world networks.
Brain Cogn. 2014 Jan 21;85C:220-230
Authors: Sun Y, Lim J, Kwok K, Bezerianos A
Changes in functional connectivity across mental states can provide richer information about human cognition than simpler univariate approaches. Here, we applied a graph theoretical approach to analyze such changes in the lower alpha (8-10Hz) band of EEG data from 26 subjects undergoing a mentally-demanding test of sustained attention: the Psychomotor Vigilance Test. Behavior and connectivity maps were compared between the first and last 5min of the task. Reaction times were significantly slower in the final minutes of the task, showing a clear time-on-task effect. A significant increase was observed in weighted characteristic path length, a measure of the efficiency of information transfer within the cortical network. This increase was correlated with reaction time change. Functional connectivity patterns were also estimated on the cortical surface via source localization of cortical activities in 26 predefined regions of interest. Increased characteristic path length was revealed, providing further support for the presence of a reshaped global topology in cortical connectivity networks under fatigue state. Additional analysis showed an asymmetrical pattern of connectivity (right>left) in fronto-parietal regions associated with sustained attention, supporting the right-lateralization of this function. Interestingly, in the fatigue state, significance decreases were observed in left, but not right fronto-parietal connectivity. Our results indicate that functional network organization can change over relatively short time scales with mental fatigue, and that decreased connectivity has a meaningful relationship with individual difference in behavior and performance.
PMID: 24463002 [PubMed - as supplied by publisher]
A role for sorting nexin 27 in AMPA receptor trafficking.
Nat Commun. 2014 Jan 24;5:3176
Authors: Loo LS, Tang N, Al-Haddawi M, Stewart Dawe G, Hong W
Sorting nexin 27 (SNX27), a PDZ domain-containing endosomal protein, was recently shown to modulate glutamate receptor recycling in Down's syndrome. However, the precise molecular role of SNX27 in GluA1 trafficking is unclear. Here we report that SNX27 is enriched in dendrites and spines, along with recycling endosomes. Significantly, the mobilization of SNX27 along with recycling endosomes into spines was observed. Mechanistically, SNX27 interacts with K-ras GTPase via the RA domain; and following chemical LTP stimuli, K-ras is recruited to SNX27-enriched endosomes through a Ca(2+)/CaM-dependent mechanism, which in turn drives the synaptic delivery of homomeric GluA1 receptors. Impairment of SNX27 prevents LTP and associated trafficking of AMPARs. These results demonstrate a role for SNX27 in neuronal plasticity, provide a molecular explanation for the K-ras signal during LTP and identify SNX27 as the PDZ-containing molecular linker that couples the plasticity stimuli to the delivery of postsynaptic cargo.
PMID: 24458027 [PubMed - in process]
Neural correlates of task-related changes in physiological tremor.
J Neurophysiol. 2013 Jul;110(1):170-6
Authors: Laine CM, Negro F, Farina D
Appropriate control of muscle contraction requires integration of command signals with sensory feedback. Sensorimotor integration is often studied under conditions in which muscle force is controlled with visual feedback. While it is known that alteration of visual feedback can influence task performance, the underlying changes in neural drive to the muscles are not well understood. In this study, we characterize the frequency content of force fluctuations and neural drive when production of muscle force is target guided versus self guided. In the self-guided condition, subjects performed isometric contractions of the first dorsal interosseous (FDI) muscle while slowly and randomly varying their force level. Subjects received visual feedback of their own force in order to keep contractions between 6% and 10% of maximum voluntary contraction (MVC). In the target-guided condition, subjects used a display of their previously generated force as a target to track over time. During target tracking, force tremor increased significantly in the 3-5 and 7-9 Hz ranges, compared with self-guided contractions. The underlying changes in neural drive were assessed by coherence analysis of FDI motor unit activity. During target-guided force production, pairs of simultaneously recorded motor units showed less coherent activity in the 3-5 Hz frequency range but greater coherence in the 7-9 Hz range than in the self-guided contractions. These results show that the frequency content of common synaptic input to motoneurons is altered when force production is visually guided. We propose that a change in stretch-reflex gain could provide a potential mechanism for the observed changes in force tremor and motor unit coherence.
PMID: 23596333 [PubMed - indexed for MEDLINE]
Deliver us from evil? The temptation, realities, and neuroethico-legal issues of employing assessment neurotechnologies in public safety initiatives.
Theor Med Bioeth. 2014 Jan 20;
Authors: Giordano J, Kulkarni A, Farwell J
In light of the recent events of terrorism and publicized cases of mass slayings and serial killings, there have been calls from the public and policy-makers alike for neuroscience and neurotechnology (neuroS/T) to be employed to intervene in ways that define and assess, if not prevent, such wanton acts of aggression and violence. Ongoing advancements in assessment neuroS/T have enabled heretofore unparalleled capabilities to evaluate the structure and function of the brain, yet each and all are constrained by certain technical and practical limitations. In this paper, we present an overview of the capabilities and constraints of current assessment neuroS/T, address neuro-ethical and legal issues fostered by the use and potential misuse of these approaches, and discuss how neuroethics may inform science and the law to guide right and sound applications of neuroS/T to "deliver us from evil" while not being led into temptations of ampliative claims and inapt use.
PMID: 24442931 [PubMed - as supplied by publisher]
Modes and regulation of endocytic membrane retrieval in mouse auditory hair cells.
J Neurosci. 2014 Jan 15;34(3):705-16
Authors: Neef J, Jung S, Wong AB, Reuter K, Pangrsic T, Chakrabarti R, Kügler S, Lenz C, Nouvian R, Boumil RM, Frankel WN, Wichmann C, Moser T
Synaptic vesicle recycling sustains high rates of neurotransmission at the ribbon-type active zones (AZs) of mouse auditory inner hair cells (IHCs), but its modes and molecular regulation are poorly understood. Electron microscopy indicated the presence of clathrin-mediated endocytosis (CME) and bulk endocytosis. The endocytic proteins dynamin, clathrin, and amphiphysin are expressed and broadly distributed in IHCs. We used confocal vglut1-pHluorin imaging and membrane capacitance (Cm) measurements to study the spatial organization and dynamics of IHC exocytosis and endocytosis. Viral gene transfer expressed vglut1-pHluorin in IHCs and targeted it to synaptic vesicles. The intravesicular pH was ?6.5, supporting only a modest increase of vglut1-pHluorin fluorescence during exocytosis and pH neutralization. Ca(2+) influx triggered an exocytic increase of vglut1-pHluorin fluorescence at the AZs, around which it remained for several seconds. The endocytic Cm decline proceeded with constant rate (linear component) after exocytosis of the readily releasable pool (RRP). When exocytosis exceeded three to four RRP equivalents, IHCs additionally recruited a faster Cm decline (exponential component) that increased with the amount of preceding exocytosis and likely reflects bulk endocytosis. The dynamin inhibitor Dyngo-4a and the clathrin blocker pitstop 2 selectively impaired the linear component of endocytic Cm decline. A missense mutation of dynamin 1 (fitful) inhibited endocytosis to a similar extent as Dyngo-4a. We propose that IHCs use dynamin-dependent endocytosis via CME to support vesicle cycling during mild stimulation but recruit bulk endocytosis to balance massive exocytosis.
PMID: 24431429 [PubMed - in process]
Flavoprotein autofluorescence imaging of visual system activity in zebra finches and mice.
PLoS One. 2014;9(1):e85225
Authors: Michael N, Bischof HJ, Löwel S
Large-scale brain activity patterns can be visualized by optical imaging of intrinsic signals (OIS) based on activity-dependent changes in the blood oxygenation level. Another method, flavoprotein autofluorescence imaging (AFI), exploits the mitochondrial flavoprotein autofluorescence, which is enhanced during neuronal activity. In birds, topographic mapping of visual space has been shown in the visual wulst, the avian homologue of the mammalian visual cortex by using OIS. We here applied the AFI method to visualize topographic maps in the visual wulst because with OIS, which depends on blood flow changes, blood vessel artifacts often obscure brain activity maps. We then compared both techniques quantitatively in zebra finches and in C57Bl/6J mice using the same setup and stimulation conditions. In addition to experiments with craniotomized animals, we also examined mice with intact skull (in zebra finches, intact skull imaging is not feasible probably due to the skull construction). In craniotomized animals, retinotopic maps were obtained by both methods in both species. Using AFI, artifacts caused by blood vessels were generally reduced, the magnitude of neuronal activity significantly higher and the retinotopic map quality better than that obtained by OIS in both zebra finches and mice. In contrast, our measurements in non-craniotomized mice did not reveal any quantitative differences between the two methods. Our results thus suggest that AFI is the method of choice for investigations of visual processing in zebra finches. In mice, however, if researchers decide to use the advantages of imaging through the intact skull, they will not be able to exploit the higher signals obtainable by the AFI-method.
PMID: 24400130 [PubMed - in process]
EEG alpha activity is associated with individual differences in post-break improvement.
Neuroimage. 2013 Aug 1;76:81-9
Authors: Lim J, Quevenco FC, Kwok K
Continuous EEG activity has been used increasingly as a marker of mental and cognitive states, with previous work linking particular neural patterns to conditions of arousal or fatigue. This approach is more commonly used to assess task-related, as opposed to resting-state activity. In this study, we recorded the EEG of 31 healthy individuals as they performed two sessions of a 65-minute auditory oddball task, one with, and one without a 5-minute break opportunity. Over the course of the task, reaction times, as well as EEG power in theta and lower alpha bands increased in both conditions, but did not differ significantly between conditions. Over the period of the break, delta and theta EEG activity decreased significantly in comparison with activity in the equivalent period in the no-break condition. Individual differences in response to the break were observed, with approximately half the subjects showing an improvement, and half showing a decline. These individual differences were correlated both with decreases in theta activity, as well as resting upper alpha power during the period of the break. Our results suggest that tonic EEG activity during resting periods is meaningfully related to behavioral change between individuals based on physiological or psychological factors that remain to be explored.
PMID: 23523810 [PubMed - indexed for MEDLINE]
How do we recognise who is speaking?
Front Biosci (Schol Ed). 2014;6:92-109
Authors: Mathias SR, von Kriegstein K
The human brain effortlessly extracts a wealth of information from natural speech, which allows the listener to both understand the speech message and recognise who is speaking. This article reviews behavioural and neuroscientific work that has attempted to characterise how listeners achieve speaker recognition. Behavioural studies suggest that the action of a speaker's glottal folds and the overall length of their vocal tract carry important voice-quality information. Although these cues are useful for discriminating and recognising speakers under certain circumstances, listeners may use virtually any systematic feature for recognition. Neuroscientific studies have revealed that speaker recognition relies upon a predominantly right-lateralised network of brain regions. Specifically, the posterior parts of superior temporal sulcus appear to perform some of the acoustical analyses necessary for the perception of speaker and message, whilst anterior portions may play a more abstract role in perceiving speaker identity. This voice-processing network is supported by direct, early connections to non-auditory regions, such as the visual face-sensitive area in the fusiform gyrus, which may serve to optimize person recognition.
PMID: 24389264 [PubMed - in process]
What do clinicians need from a rehabilitation treatment taxonomy? An alternate approach for describing treatment content versus process.
Arch Phys Med Rehabil. 2014 Jan;95(1 Suppl):S74-6
Authors: Fasoli SE, Chen CC
Clinician feedback and thought processes about treatment classification and description will aid development of the rehabilitation treatment taxonomy (RTT) presented in this supplement. Here, we discuss comparisons between the proposed RTT and an inductive practice-based evidence (PBE) model used to describe rehabilitation treatments. Interviews with clinicians well versed with PBE highlight the complexity of rehabilitation treatments, and bring to light potential advantages and challenges of a deductive, theory-driven classification to uncover the black box of rehabilitation.
PMID: 24370328 [PubMed - in process]
A non-parametric Bayesian approach for clustering and tracking non-stationarities of neural spikes.
J Neurosci Methods. 2013 Dec 12;
Authors: Shalchyan V, Farina D
-Background Neural spikes from multiple neurons recorded in a multi-unit signal are usually separated by clustering. Drifts in the position of the recording electrode relative to the neurons over time cause gradual changes in the position and shapes of the clusters, challenging the clustering task. By dividing the data into short time intervals, Bayesian tracking of the clusters based on Gaussian cluster model has been previously proposed. However, the Gaussian cluster model is often not verified for neural spikes. -New Method We present a Bayesian clustering approach that makes no assumptions on the distribution of the clusters and use kernel-based density estimation of the clusters in every time interval as a prior for Bayesian classification of the data in the subsequent time interval. -Comparison with Existing Methods The proposed method was tested and compared to Gaussian model-based approach for cluster tracking by using both simulated and experimental datasets. -Results The results showed that the proposed non-parametric kernel-based density estimation of the clusters outperformed the sequential Gaussian model fitting in both simulated and experimental data tests. -Conclusions Using Non-parametric kernel density-based clustering that makes no assumptions on the distribution of the clusters enhances the ability of tracking cluster non-stationarity over time with respect to the Gaussian cluster modeling approach.
PMID: 24333470 [PubMed - as supplied by publisher]
Neurovascular coupling: in vivo optical techniques for functional brain imaging.
Biomed Eng Online. 2013;12:38
Authors: Liao LD, Tsytsarev V, Delgado-Martínez I, Li ML, Erzurumlu R, Vipin A, Orellana J, Lin YR, Lai HY, Chen YY, Thakor NV
Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology.
PMID: 23631798 [PubMed - indexed for MEDLINE]
Identification of common synaptic inputs to motor neurons from the rectified electromyogram.
J Physiol. 2013 May 15;591(Pt 10):2403-18
Authors: Farina D, Negro F, Jiang N
Oscillatory common inputs of cortical or peripheral origin can be identified from the motor neuron output with coherence analysis. Linear transmission is possible despite the motor neuron non-linearity because the same input is sent commonly to several neurons. Because of the linear transmission, common input components to motor neurons can be investigated from the surface EMG, for example by EEG-EMG or EMG-EMG coherence. In these studies, there is an open debate on the utility and appropriateness of EMG rectification. The present study addresses this issue using an analytical, simulation and experimental approach. The main novel theoretical contribution that we report is that the spectra of both the rectified and the raw EMG contain input spectral components to motor neurons. However, they differ by the contribution of amplitude cancellation which influences the rectified EMG spectrum when extracting common oscillatory inputs. Therefore, the degree of amplitude cancellation has an impact on the effectiveness of EMG rectification in extracting input spectral peaks. The theoretical predictions were exactly confirmed by realistic simulations of a pool of motor neurons innervating a muscle in a cylindrical volume conductor of EMG generation and by experiments conducted on the first dorsal interosseous and the abductor pollicis brevis muscles of seven healthy subjects during pinching. It was concluded that when the contraction level is relatively low, EMG rectification may be preferable for identifying common inputs to motor neurons, especially when the energy of the action potentials in the low frequency range is low. Nonetheless, different levels of cancellation across conditions influence the relative estimates of the degree of linear transmission of oscillatory inputs to motor neurons when using the rectified EMG.
PMID: 23507877 [PubMed - indexed for MEDLINE]
The role of actigraphy in the assessment of primary insomnia: a retrospective study.
Sleep Med. 2013 Nov 15;
Authors: Natale V, Léger D, Martoni M, Bayon V, Erbacci A
OBJECTIVE: The aim of our study was to evaluate quantitative actigraphic criteria obtained using the Actiwatch device (AW64; Cambridge Neurotechnology Ltd., Cambridge, UK) to differentiate participants with insomnia from normal sleepers.
METHODS: In our retrospective study, we recovered 493 actigraphic records from two sleep measure databases of patients with insomnia (n=151) and one of normal sleepers (n=342). We considered the following actigraphic sleep parameters: time in bed (TIB), sleep-onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), sleep efficiency (SE), number of awakenings (NWAK), terminal wakefulness (TWAK), fragmentation index (FI), and mean motor activity (MA). We also considered two actigraphic circadian indexes: interdaily stability and intradaily variability. Using the Youden index, we calculated the quantitative actigraphic criteria that performed best for each actigraphic sleep parameter. Finally, we created receiver operating characteristic curves to test the accuracy of each criterion identified.
RESULTS: All sleep parameters except TST and TWAK differentiated the two groups of participants, allowing calculation of quantitative actigraphic criteria. There were no differences in the circadian indices.
CONCLUSIONS: The quantitative actigraphic criteria obtained in our study were not the same as those obtained previously with a different device, suggesting the need to adopt shared technical solutions for actigraphy.
PMID: 24325809 [PubMed - as supplied by publisher]
Comparison of 7 versus 14 days wrist actigraphy monitoring in a sleep disorders clinic population.
Chronobiol Int. 2013 Dec 4;
Authors: Briscoe S, Hardy E, Pengo MF, Kosky C, Williams AJ, Hart N, Steier J
Wrist actigraphy is a valid measure to assess sleep and circadian rhythm abnormalities. It is listed in the diagnostic criteria for sleep disorders where single night polysomnography is insufficient (ICSD-2). However, an optimal recording time remains unclear. We hypothesised that seven days would provide sufficient data for analysis, similar to recordings for 14 days. We analysed three consecutive years of actigraphy data obtained within a tertiary sleep referral centre. Data were recorded continuously for two weeks using an AW4 actiwatch (Cambridge NeuroTechnology, Cambridge, UK; Mini Mitter Co, Sunriver, OR). Parameters, including sleep efficiency (SE), sleep latency (SL), sleep fragmentation index (SFI), total sleep time (TST) and wake after sleep onset (WASO) were analysed using GraphPad Prism (Version 5.02, GraphPad Software Inc, San Diego, CA) and classified into week one, week two and an overall average for the duration of 14 days. In addition, two experienced consultants working in the sleep laboratory compared the results of week one versus week two independently, visually analysing the data for circadian rhythmicity and fragmentation of the pattern, allowing calculation of the intraclass correlation coefficient (ICC), ?. The actigraphies of 239 patients (51.9% male; age 42 (16) years) were analysed. There was no difference in SE, SL, SFI or WASO between week one, week two and 14 days average recording. A small difference was found between TST week one (399.9 minutes, 95% CI 389.9-409.9 minutes) and TST week two (388.7 minutes, 95% CI 378.3-399.1 minutes), but not between TST for 14 days average recording (394.3 minutes, 95% CI 384.7-403.9 minutes) and either week. Independent scorers achieved a good agreement in the rhythmicity of the sleep pattern (ICC ? 0.734, p?<?0.001) and a low agreement for the fragmentation of the pattern (ICC ? 0.380, p?<?0.001). One week of wrist actigraphy recording provides similar data to two week actigraphies, despite subtle differences between the weeks. One week wrist actigraphy could be recommended as standard compared to longer recordings to maximise efficiency of the clinical service. Further studies are required to validate our results in specific clinical subgroups.
PMID: 24304408 [PubMed - as supplied by publisher]
Brain-machine interface (BMI) - application to neurological disorders.
Rinsho Shinkeigaku. 2013;53(11):962-5
Authors: Yoshimine T, Yanagisawa T, Hirata M
Brain-machine interface (BMI) is a new technology to receive input from the brain which is translated to operate a computer or other external device in real time. After significant progress during the recent 10 years, this technology is now very close to the clinical use to restore neural functions of patients with severe neurologic impairment. This technology is also a strong tool to investigate the mode of neuro-signal processing in the brain and to understand the mechanism of neural dysfunction which leads to the development of novel neurotechnology for the treatment of various sorts of neurological disorders.
PMID: 24291847 [PubMed - in process]
In vivo testing of a 3D bifurcating microchannel scaffold inducing separation of regenerating axon bundles in peripheral nerves.
J Neural Eng. 2013 Dec;10(6):066018
Authors: Stoyanova II, van Wezel RJ, Rutten WL
Artificial nerve guidance channels enhance the regenerative effectiveness in an injured peripheral nerve but the existing design so far has been limited to basic straight tubes simply guiding the growth to bridge the gap. Hence, one of the goals in development of more effective neuroprostheses is to create bidirectional highly selective neuro-electronic interface between a prosthetic device and the severed nerve. A step towards improving selectivity for both recording and stimulation have been made with some recent in vitro studies which showed that three-dimensional (3D) bifurcating microchannels can separate neurites growing on a planar surface and bring them into contact with individual electrodes. Since the growing axons in vivo have the innate tendency to group in bundles surrounded by connective tissue, one of the big challenges in neuro-prosthetic interface design is how to overcome it. Therefore, we performed experiments with 3D bifurcating guidance scaffolds implanted in the sciatic nerve of rats to test if this new channel architecture could trigger separation pattern of ingrowth also in vivo. Our results showed that this new method enabled the re-growth of neurites into channels with gradually diminished width (80, 40 and 20 µm) and facilitated the separation of the axonal bundles with 91% success. It seems that the 3D bifurcating scaffold might contribute towards conveying detailed neural control and sensory feedback to users of prosthetic devices, and thus could improve the quality of their daily life.
PMID: 24280623 [PubMed - in process]
On the interpretation of weight vectors of linear models in multivariate neuroimaging.
Neuroimage. 2013 Nov 14;
Authors: Haufe S, Meinecke F, Görgen K, Dähne S, Haynes JD, Blankertz B, Bießmann F
The increase in spatiotemporal resolution of neuroimaging devices is accompanied by a trend towards more powerful multivariate analysis methods. Often it is desired to interpret the outcome of these methods with respect to the cognitive processes under study. Here we discuss which methods allow for such interpretations, and provide guidelines for choosing an appropriate analysis for a given experimental goal: For a surgeon who needs to decide where to remove brain tissue it is most important to determine the origin of cognitive functions and associated neural processes. In contrast, when communicating with paralyzed or comatose patients via brain-computer interfaces, it is most important to accurately extract the neural processes specific to a certain mental state. These equally important but complementary objectives require different analysis methods. Determining the origin of neural processes in time or space from the parameters of a data-driven model requires what we call a forward model of the data; such a model explains how the measured data was generated from the neural sources. Examples are general linear models (GLMs). Methods for the extraction of neural information from data can be considered as backward models, as they attempt to reverse the data generating process. Examples are multivariate classifiers. Here we demonstrate that the parameters of forward models are neurophysiologically interpretable in the sense that significant nonzero weights are only observed at channels the activity of which is related to the brain process under study. In contrast, the interpretation of backward model parameters can lead to wrong conclusions regarding the spatial or temporal origin of the neural signals of interest, since significant nonzero weights may also be observed at channels the activity of which is statistically independent of the brain process under study. As a remedy for the linear case, we propose a procedure for transforming backward models into forward models. This procedure enables the neurophysiological interpretation of the parameters of linear backward models. We hope that this work raises awareness for an often encountered problem and provides a theoretical basis for conducting better interpretable multivariate neuroimaging analyses.
PMID: 24239590 [PubMed - as supplied by publisher]
Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates.
J Neural Eng. 2013 Nov 12;10(6):066014
Authors: Barrese JC, Rao N, Paroo K, Triebwasser C, Vargas-Irwin C, Franquemont L, Donoghue JP
Objective. Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach. Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results. Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. Significance. This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade.
PMID: 24216311 [PubMed - as supplied by publisher]
Neurotechnology: BRAIN storm.
Nature. 2013 Nov 7;503(7474):26-8
Authors: Shen H
PMID: 24201265 [PubMed - in process]
Optogenetic stimulation effectively enhances intrinsically generated network synchrony.
Front Neural Circuits. 2013;7:167
Authors: El Hady A, Afshar G, Bröking K, Schlüter OM, Geisel T, Stühmer W, Wolf F
Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson's disease, and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened, reduced, or even abolished. We combined electrical recording using multi-electrode array with optical stimulation of cultured channelrhodopsin-2 transducted hippocampal neurons to study and manipulate network burst synchronization. We found low frequency photo-stimulation protocols that are sufficient to induce potentiation of network bursting, modifying bursting dynamics, and increasing interneuronal synchronization. Surprisingly, slowly fading-in light stimulation, which substantially delayed and reduced light-driven spiking, was at least as effective in reorganizing network dynamics as much stronger pulsed light stimulation. Our study shows that mild stimulation protocols that do not enforce particular activity patterns onto the network can be highly effective inducers of network-level plasticity.
PMID: 24155695 [PubMed - as supplied by publisher]
Estimating the modulatory effects of nanoparticles on neuronal circuits using computational upscaling.
Int J Nanomedicine. 2013;8:3559-3572
Authors: Busse M, Stevens D, Kraegeloh A, Cavelius C, Vukelic M, Arzt E, Strauss DJ
BACKGROUND: Beside the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug delivery schemes are already in clinical trials. However the influence of the nanoparticles themselves is still unknown in medical applications, especially for complex interactions in neural systems. The aim of this study was to investigate in vitro effects of coated silver nanoparticles (cAgNP) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects on neuronal circuits.
METHODS: We first performed patch clamp measurements to investigate the effects of nanosized silver particles, surrounded by an organic coating, on excitability of single cells. We then determined which parameters were altered by exposure to those nanoparticles using the Hodgkin-Huxley model of the sodium current. As a third step, we integrated those findings into a well-defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAgNP, in silico.
RESULTS: We observed rapid suppression of sodium currents after exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium currents we identified the parameters likely affected by cAgNP. We then examined the effects of such changes on the activity of networks. In silico network modeling indicated effects of local cAgNP application on firing patterns in all neurons in the circuit.
CONCLUSION: Our sodium current simulation shows that suppression of sodium currents by cAgNP results primarily by a reduction in the amplitude of the current. The network simulation shows that locally cAgNP-induced changes result in changes in network activity in the entire network, indicating that local application of cAgNP may influence the activity throughout the network.
PMID: 24115840 [PubMed - as supplied by publisher]
Computational models of optogenetic tools for controlling neural circuits with light.
Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:5934-5937
Authors: Nikolic K, Jarvis S, Grossman N, Schultz S
Optogenetics is a new neurotechnology innovation based on the creation of light sensitivity of neurons using gene technologies and remote light activation. Optogenetics allows for the first time straightforward targeted neural stimulation with practically no interference between multiple stimulation points since either light beam can be finely confined or the expression of light sensitive ion channels and pumps can be genetically targeted. Here we present a generalised computational modeling technique for various types of optogenetic mechanisms, which was implemented in the NEURON simulation environment. It was demonstrated on the example of a two classical mechanisms for cells optical activation and silencing: channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR).We theoretically investigate the dynamics of the neural response of a layer 5 cortical pyramidal neuron (L5) to four different types of illuminations: 1) wide-field whole cell illumination 2) wide-field apical dendritic illumination 3) focal somatic illumination and 4) focal axon initial segment (AIS) illumination. We show that whole-cell illumination of halorhodopsin most effectively hyperpolarizes the neuron and is able to silence the cell even when driving input is present. However, when channelrhodopsin-2 and halorhodopsin are concurrently active, the relative location of each illumination determines whether the response is modulated with a balance towards depolarization. The methodology developed in this study will be significant to interpret and design optogenetic experiments and in the field of neuroengineering in general.
PMID: 24111090 [PubMed - as supplied by publisher]
Fragmentation of slow wave sleep after onset of complete locked-in state.
J Clin Sleep Med. 2013 Sep;9(9):951-3
Authors: Soekadar SR, Born J, Birbaumer N, Bensch M, Halder S, Murguialday AR, Gharabaghi A, Nijboer F, Schölkopf B, Martens S
UNLABELLED: Locked-in syndrome (LIS) as a result of brainstem lesions or progressive neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), is a severe medical condition in which a person is fully conscious but unable to move or talk. LIS can transition into complete locked-in syndrome (CLIS) in which residual abilities to communicate through muscle twitches are entirely lost. It is unknown how CLIS affects circadian rhythm and sleep/wake patterns. Here we report a 39-year-old ALS patient who transitioned from LIS to CLIS while brain activity was continuously recorded using electrocorticography (ECoG) over one month. While we found no circadian rhythm in heart rate and body temperature, transition into CLIS was associated with increased fragmentation of slow wave sleep (SWS) across the day. Total time in SWS did not change. SWS fragmentation might reflect progressive circadian system impairment and should be considered as a factor further limiting communication capabilities in these patients.
CITATION: Soekadar SR; Born J; Birbaumer N; Bensch M; Halder S; Murguialday AR; Gharabaghi A; Nijboer F; Schölkopf B; Martens S. Fragmentation of slow wave sleep after onset of complete locked-in state. J Clin Sleep Med 2013;9(9):951-953.
PMID: 23997708 [PubMed - in process]