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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]
Nonlocal two dimensional denoising of frequency specific chirp evoked ABR single trials.
Conf Proc IEEE Eng Med Biol Soc. 2012;2012:2527-30
Authors: Schubert JK, Teuber T, Steidl G, Strauss DJ, Corona-Strauss FI
Recently, we have shown that denoising evoked potential (EP) images is possible using two dimensional diffusion filtering methods. This restoration allows for an integration of regularities over multiple stimulations into the denoising process. In the present work we propose the nonlocal means (NLM) method for EP image denoising. The EP images were constructed using auditory brainstem responses (ABR) collected in young healthy subjects using frequency specific and broadband chirp stimulations. It is concluded that the NLM method is more efficient than conventional approaches in EP imaging denoising, specially in the case of ABRs, where the relevant information can be easily masked by the ongoing EEG activity, i.e., signals suffer from rather low signal-to-noise ratio SNR. The proposed approach is for the a posteriori denoising of single trials after the experiment and not for real time applications.
PMID: 23366439 [PubMed - indexed for MEDLINE]
Modeling the influences of nanoparticles on neural field oscillations in thalamocortical networks.
Conf Proc IEEE Eng Med Biol Soc. 2012;2012:1230-3
Authors: Busse M, Kraegeloh A, Arzt E, Strauss DJ
The purpose of this study is twofold. First, we present a simplified multiscale modeling approach integrating activity on the scale of ionic channels into the spatiotemporal scale of neural field potentials: Resting upon a Hodgkin-Huxley based single cell model we introduced a neuronal feedback circuit based on the Llinás-model of thalamocortical activity and binding, where all cell specific intrinsic properties were adopted from patch-clamp measurements. In this paper, we expand this existing model by integrating the output to the spatiotemporal scale of field potentials. Those are supposed to originate from the parallel activity of a variety of synchronized thalamocortical columns at the quasi-microscopic level, where the involved neurons are gathered together in units. Second and more important, we study the possible effects of nanoparticles (NPs) that are supposed to interact with thalamic cells of our network model. In two preliminary studies we demonstrated in vitro and in vivo effects of NPs on the ionic channels of single neurons and thereafter on neuronal feedback circuits. By means of our new model we assumed now NPs induced changes on the ionic currents of the involved thalamic neurons. Here we found extensive diversified pattern formations of neural field potentials when comparing to the modeled activity without neuromodulating NPs addition. This model provides predictions about the influences of NPs on spatiotemporal neural field oscillations in thalamocortical networks. These predictions can be validated by high spatiotemporal resolution electrophysiological measurements like voltage sensitive dyes and multiarray recordings.
PMID: 23366120 [PubMed - indexed for MEDLINE]
Tissue-Compliant Neural Implant from Microfabricated LBL Nanocomposite.
ACS Nano. 2013 Aug 9;
Authors: Zhang H, Patel PR, Xie Z, Swanson S, Wang X, Kotov NA
Current neural prosthetic devices (NPDs) induce chronic inflammation due to complex mechanical and biological reactions related to staggering discrepancies of mechanical properties with neural tissue. Relatively large size of the implants and traumas to blood-brain barrier contribute to inflammation reactions as well. Mitigation of these problems and the realization of long-term brain interface require a new generation of NPDs fabricated from flexible materials compliant with the brain tissue. However such materials will need to display hard-to-combine mechanical and electrical properties which are not available in the toolbox of classical neurotechnology. Moreover, these new materials will concomitantly demand different methods of (a) device micromanufacturing and (b) surgical implantation in brains because currently used processes take advantage of high stiffness of the devices. Carbon nanotubes (CNTs) serve as a promising foundation for such materials because of their record mechanical and electrical properties but CNT-based tissue-compliant devices have not been realized yet. In this study, we formalize the mechanical requirements to tissue-compliant implants based on critical rupture strength of brain tissue and demonstrate that miniature CNT-based devices can satisfy these requirements. We fabricated them using MEMS-like technology and miniaturized them so that at least two dimensions of the electrodes would be comparable to brain tissue cells. The nanocomposite-based flexible neural electrodes were implanted into rat motor cortex using surgical procedure specifically designed for soft tissue-compliant implants. The post-surgery implant localization in motor cortex was successfully visualized with magnetic resonance and photoacoustic imaging. In vivo functionality was demonstrated by successful registration of the low frequency neural recording in live brain of anesthetized rats. Investigation of inflammation processes around these electrodes will be required to establish their prospects as long-term neural electrodes.
PMID: 23930825 [PubMed - as supplied by publisher]
Triangulating perspectives on functional neuroimaging for disorders of mental health.
BMC Psychiatry. 2013 Aug 8;13(1):208
Authors: Anderson JA, Mizgalewicz A, Illes J
BACKGROUND: Functional neuroimaging is being used in clinical psychiatry today despite the vigorous objections of many in the research community over issues of readiness. To date, a systematic examination of the perspectives of key stakeholders involved in this debate has not yet been attempted. To this fill this gap, we interviewed investigators who conduct functional neuroimaging studies involving adults with mood disorders, schizophrenia, obsessive compulsive disorder, and/or attention deficit hyperactivity disorder, providers who offer clinical neuroimaging services in the open marketplace, and consumers of these services, in order to understand perspectives underlying different views and practices.
METHODS: Semi-structured interviews were conducted over the telephone. Verbal consent was obtained and all interviews were audio recorded. Interviews of investigators and service providers followed the same interview guide. A separate set of questions was developed for consumers. All interviews were transcribed and made software ready. We applied the qualitative methodology of constant comparison to analyze the data, whereby two researchers independently analyzed the results into textual themes. Coding discrepancies were discussed until consensus was achieved.
RESULTS: Investigators, service providers, and consumers held many common perspectives about the potential or actual risks and benefits of functional neuroimaging for mental illness. However, we also found striking divergences. Service providers focused on the challenges posed by the persistence of symptoms based diagnostic categories, whereas the limitations of the science in this area was the challenge noted most frequently by investigators. The majority of consumers stated that their expectations were met.
CONCLUSION: Our findings point toward a fundamental tension between academic investigators on the one hand, and commercial service providers and their customers on the other. This scenario poses dangers to the communities directly involved, and to public trust in science and medicine more generally. We conclude with recommendations for work that needs to be done to minimize tensions and maximize the potential of neurotechnology through concerted efforts to respect its limitations while leveraging the strengths, investments, and hopes of each stakeholder group.
PMID: 23924295 [PubMed - as supplied by publisher]
Ghrelin stimulates synaptic formation in cultured cortical networks in a dose-dependent manner.
Regul Pept. 2013 Jul 24;
Authors: Stoyanova II, le Feber J, Rutten WL
Ghrelin was initially related to appetite stimulation and growth hormone secretion. However, it also has a neuroprotective effect in neurodegenerative diseases and regulates cognitive function. The cellular basis of these processes are related to synaptic efficacy and plasticity. Previous studies indicated that ghrelin has an excitatory effect on neuronal activity, and stimulates synaptic plasticity in vivo. Plasticity in the adult brain occurs in many different ways, including changes in synapse morphology and number. Therefore, we used in vitro neuronal cultures to investigate how ghrelin affects synaptogenesis. We used dissociated cortical cultures of newborn rats, chronically treated with different doses of ghrelin (0.5, 1, 1.5 and 2?M). After one-, two-, three- or four weeks cultures were immunostained for the presynaptic marker synaptophysin. In parallel, additional groups of non-treated cultures were immunostained for detection of ghrelin receptor (GHSR1). During development, GHSR1was increasingly expressed in all type of neurons, as well as the synaptophysin. Synaptic density depended on ghrelin concentration, and was much higher than in controls in all age groups. In conclusion, ghrelin leads to earlier network formation in dissociated cortical networks and an increase in number of synapses. The effect is probably mediated by GHSR1. These findings suggest that ghrelin may provide a novel therapeutic strategy for the treatment of disorders related to synaptic impairment.
PMID: 23892033 [PubMed - as supplied by publisher]
Support of a patient-specific therapeutical acoustic stimulation in tinnitus by numerical modeling.
Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5578-81
Authors: Haab L, Scheerer M, Ruckert J, Hannemann R, Strauss DJ
The pathogenesis of tinnitus involves multiple hierarchical levels of auditory processing and appraisal of sensory saliency. Early tinnitus onset is most likely attributed to homeostatic plasticity in the periphery, while the chronification and decompensation are tightly linked to brain areas for the allocation of attentional resources, such as e.g., the thalamocortical feedback loops and the limbic system. Increased spontaneous firing after sensory deafferentation might be sufficient to generate a phantom perception, yet the question why not every peripheral hearing loss automatically elicits a tinnitus sensation is still to be addressed. Utilizing quantitative modeling of multiple hierarchical levels in the auditory pathway, we demonstrate the effects of lateral inhibition on increased spontaneous firing and the resulting elevation of firing regularity and synchronization of neural activity. The presented therapeutical approach is based on the idea of disrupting the heightened regularity of the neural population response in the tinnitus frequency range. This neural activity regularity depends on lateral dispersion of common noise and thus is susceptible for edge effects and might be influenced by a change in neural activity in bordering frequency ranges by fitted acoustical stimulation. We propose the use of patient specifically adapted tailor-made notched acoustic stimulation, utilizing modeling results for the optimal adjustment of the stimulation frequencies to archive a therapeutical edge-effect.
PMID: 23367193 [PubMed - indexed for MEDLINE]
Seizure detection on/off system using rats' ECoG.
Conf Proc IEEE Eng Med Biol Soc. 2012;2012:4688-91
Authors: Park YS, Netoff TI, Yang X, Parhi KK
We present an enhanced algorithm for seizure onset and offset detection in rats' ECoG. Because a seizure in rats' ECoG evolves much more stereotypically than that in human, analyzing seizure evolution in rats' ECoG is advantageous to understanding the evolution process. The proposed algorithm outperforms a prior automatic seizure detection and termination system in in-vivo rats' ECoG. We improve the algorithm by using relevant frequency bands of 14-22 Hz to onsets and 7-45 Hz to offsets; by using spectral power rather than spectral amplitudes for its feature; and by replacing the 2-point moving-average filter for postprocessing with a 2(nd) order Kalman filter. Not only does the proposed algorithm provide better detection statistics, but it lowers the system's complexity by no longer requiring computation of a fast Fourier transform and by using a single structure with the two different spectral power features for onset and offset detection.
PMID: 23366974 [PubMed - indexed for MEDLINE]
Quantification of listening effort correlates in the oscillatory EEG activity: a feasibility study.
Conf Proc IEEE Eng Med Biol Soc. 2012;2012:4615-8
Authors: Bernarding C, Strauss DJ, Hannemann R, Corona-Strauss FI
So far, a generally accepted objective measure for the listening effort estimation in clinical settings is not existent. Such a measure could support the hearing aid fitting in order to reduce the listening effort in hearing impaired patients by an adequate adaption of their personal hearing aids. In the current study, we propose a new measure for the quantification of large-scale listening effort correlates. This measure takes the phase information of the ongoing oscillatory EEG activity into account. The phase was gained from the 32 channel EEG. Then, the entropy of the extracted phase was calculated. We assume that this angular entropy reflects phase synchronization effects of the ongoing activities due to an increased attention on the relevant (speech) signal. Thus, we expect that smaller values of the angular entropy reflect a more "ordered" process of the phase distribution. The new method was tested in 13 young normal hearing subjects using different auditory tasks consisting of differently adapted sentences to create different listening conditions. The results indicate that the angular entropy can be applied to reveal significantly differences between the solving and the relaxing part of the paradigm, i.e. between a more effortful and a more relaxing listening situation. It is concluded, that the further research includes the development of more effortful listening tasks in order to reveal also differences between the auditory paradigms.
PMID: 23366956 [PubMed - indexed for MEDLINE]
Advantages of closed-loop calibration in intracortical brain-computer interfaces for people with tetraplegia.
J Neural Eng. 2013 Jul 10;10(4):046012
Authors: Jarosiewicz B, Masse NY, Bacher D, Cash SS, Eskandar E, Friehs G, Donoghue JP, Hochberg LR
Objective. Brain-computer interfaces (BCIs) aim to provide a means for people with severe motor disabilities to control their environment directly with neural activity. In intracortical BCIs for people with tetraplegia, the decoder that maps neural activity to desired movements has typically been calibrated using 'open-loop' (OL) imagination of control while a cursor automatically moves to targets on a computer screen. However, because neural activity can vary across contexts, a decoder calibrated using OL data may not be optimal for 'closed-loop' (CL) neural control. Here, we tested whether CL calibration creates a better decoder than OL calibration even when all other factors that might influence performance are held constant, including the amount of data used for calibration and the amount of elapsed time between calibration and testing. Approach. Two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial performed a center-out-back task using an intracortical BCI, switching between decoders that had been calibrated on OL versus CL data. Main results. Even when all other variables were held constant, CL calibration improved neural control as well as the accuracy and strength of the tuning model. Updating the CL decoder using additional and more recent data resulted in further improvements. Significance. Differences in neural activity between OL and CL contexts contribute to the superiority of CL decoders, even prior to their additional 'adaptive' advantage. In the near future, CL decoder calibration may enable robust neural control without needing to pause ongoing, practical use of BCIs, an important step toward clinical utility.
PMID: 23838067 [PubMed - as supplied by publisher]
A musculoskeletal model of human locomotion driven by a low dimensional set of impulsive excitation primitives.
Front Comput Neurosci. 2013;7:79
Authors: Sartori M, Gizzi L, Lloyd DG, Farina D
Human locomotion has been described as being generated by an impulsive (burst-like) excitation of groups of musculotendon units, with timing dependent on the biomechanical goal of the task. Despite this view being supported by many experimental observations on specific locomotion tasks, it is still unknown if the same impulsive controller (i.e., a low-dimensional set of time-delayed excitastion primitives) can be used as input drive for large musculoskeletal models across different human locomotion tasks. For this purpose, we extracted, with non-negative matrix factorization, five non-negative factors from a large sample of muscle electromyograms in two healthy subjects during four motor tasks. These included walking, running, sidestepping, and crossover cutting maneuvers. The extracted non-negative factors were then averaged and parameterized to obtain task-generic Gaussian-shaped impulsive excitation curves or primitives. These were used to drive a subject-specific musculoskeletal model of the human lower extremity. Results showed that the same set of five impulsive excitation primitives could be used to predict the dynamics of 34 musculotendon units and the resulting hip, knee and ankle joint moments (i.e., NRMSE = 0.18 ± 0.08, and R (2) = 0.73 ± 0.22 across all tasks and subjects) without substantial loss of accuracy with respect to using experimental electromyograms (i.e., NRMSE = 0.16 ± 0.07, and R (2) = 0.78 ± 0.18 across all tasks and subjects). Results support the hypothesis that biomechanically different motor tasks might share similar neuromuscular control strategies. This might have implications in neurorehabilitation technologies such as human-machine interfaces for the torque-driven, proportional control of powered prostheses and orthoses. In this, device control commands (i.e., predicted joint torque) could be derived without direct experimental data but relying on simple parameterized Gaussian-shaped curves, thus decreasing the input drive complexity and the number of needed sensors.
PMID: 23805099 [PubMed - as supplied by publisher]
In vivo assessment of human brain oscillations during application of transcranial electric currents.
Nat Commun. 2013 Jun 21;4:2032
Authors: Soekadar SR, Witkowski M, Cossio EG, Birbaumer N, Robinson SE, Cohen LG
Brain oscillations reflect pattern formation of cell assemblies' activity, which is often disturbed in neurological and psychiatric diseases like depression, schizophrenia and stroke. In the neurobiological analysis and treatment of these conditions, transcranial electric currents applied to the brain proved beneficial. However, the direct effects of these currents on brain oscillations have remained an enigma because of the inability to record them simultaneously. Here we report a novel strategy that resolves this problem. We describe accurate reconstructed localization of dipolar sources and changes of brain oscillatory activity associated with motor actions in primary cortical brain regions undergoing transcranial electric stimulation. This new method allows for the first time direct measurement of the effects of non-invasive electrical brain stimulation on brain oscillatory activity and behavior.
PMID: 23787780 [PubMed - as supplied by publisher]
Corticotropin-releasing factor infusion into nucleus incertus suppresses medial prefrontal cortical activity and hippocampo-medial prefrontal cortical long-term potentiation.
Eur J Neurosci. 2013 May 14;
Authors: Farooq U, Rajkumar R, Sukumaran S, Wu Y, Tan WH, Dawe GS
The medial prefrontal cortex (mPFC) in the rat has been implicated in a variety of cognitive processes, including working memory and expression of fear memory. We investigated the inputs from a brain stem nucleus, the nucleus incertus (NI), to the prelimbic area of the mPFC. This nucleus strongly expresses corticotropin-releasing factor type 1 (CRF1 ) receptors and responds to stress. A retrograde tracer was used to verify connections from the NI to the mPFC. Retrogradely labelled cells in the NI expressed CRF receptors. Electrophysiological manipulation of the NI revealed that stimulation of the NI inhibited spontaneous neuronal firing in the mPFC. Similarly, CRF infusion into the NI, in order to mimic a stressful condition, inhibited neuronal firing and burst firing in the mPFC. The effect of concurrent high-frequency stimulation of the NI on plasticity in the hippocampo-prelimbic medial prefrontal cortical (HP-mPFC) pathway was studied. It was found that electrical stimulation of the NI impaired long-term potentiation in the HP-mPFC pathway. Furthermore, CRF infusion into the NI produced similar results. These findings might account for some of the extra-pituitary functions of CRF and indicate that the NI may play a role in stress-driven modulation of working memory and possibly other cognitive processes subserved by the mPFC.
PMID: 23668693 [PubMed - as supplied by publisher]
Accessing the neural drive to muscle and translation to neurorehabilitation technologies.
IEEE Rev Biomed Eng. 2012;5:3-14
Authors: Farina D, Negro F
This review describes methods for interfacing motor neurons from muscle recordings and their applications in studies on the neural control of movement and in the design of technologies for neurorehabilitation. After describing methods for accessing the neural drive to muscles in vivo in humans, we discuss the mechanisms of transmission of synaptic input into motor neuron output and of force generation. The synaptic input received by a motor neuron population is largely common among motor neurons. This allows linear transmission of the input and a reduced dimensionality of control by the central nervous system. Force is generated by low-pass filtering the neural signal sent to the muscle. These concepts on neural control of movement are used for the development of neurorehabilitation technologies, which are discussed with representative examples on movement replacement, restoration, and neuromodulation. It is concluded that the analysis of the output of spinal motor neurons from muscle signals provides a unique means for understanding the neural coding of movement in vivo in humans and thus for reproducing this code artificially with the aim of restoring lost or impaired motor functions.
PMID: 23231985 [PubMed - indexed for MEDLINE]
Effectiveness of an 8-week exercise programme on pain and specificity of neck muscle activity in patients with chronic neck pain: A randomized controlled study.
Eur J Pain. 2013 May 6;
Authors: Falla D, Lindstrøm R, Rechter L, Boudreau S, Petzke F
BACKGROUND: Although exercise can be effective for relief of neck pain, little is known about the effect of exercise on the neural control of neck muscles. METHODS: A randomized controlled trial was conducted on 46 women with chronic neck pain to investigate the immediate effectiveness of an 8-week exercise programme on pain and directional specificity of neck muscle activity. At baseline, the patients completed questionnaires including the neck disability index (NDI) and performed a circular contraction of their head in the horizontal plane at 15?N force, with continuous change in force direction in the range 0-360°. Electromyography (EMG) was recorded from the sternocleidomastoid (SCM) and splenius capitis (SCap) muscles. Tuning curves of the EMG amplitude were computed, which depicts muscle activity over a range of force directions. The mean point of the tuning curves defined a directional vector, which determined the specificity of muscle activity. Patients were randomly assigned either to a training or control group. RESULTS: A significant between-group difference in the change in NDI was observed. A reduction in NDI was observed following training (pre: 18.2?±?7.4; post: 14.1?±?6.5; p?<?0.01) but not for the control group (pre: 17.5?±?6.3; post: 16.6?±?7.4). The training group showed higher specificity of muscle activity post-intervention (pre: 18.6?±?9.8%, post: 24.7?±?14.3%; p?<?0.05), whereas no change occurred for the control group (pre: 19.4?±?11.9%, post: 18.2?±?10.1%). CONCLUSION: An exercise programme that aims to enhance motor control of the cervical spine improves the specificity of neck muscle activity and reduces pain and disability in patients with neck pain.
PMID: 23649799 [PubMed - as supplied by publisher]
Mitochondrial Exchanger NCLX Plays a Major Role in the Intracellular Ca2+ Signaling, Gliotransmission, and Proliferation of Astrocytes.
J Neurosci. 2013 Apr 24;33(17):7206-19
Authors: Parnis J, Montana V, Delgado-Martinez I, Matyash V, Parpura V, Kettenmann H, Sekler I, Nolte C
Mitochondria not only provide cells with energy, but are central to Ca(2+) signaling. Powered by the mitochondrial membrane potential, Ca(2+) enters the mitochondria and is released into the cytosol through a mitochondrial Na(+)/Ca(2+) exchanger. We established that NCLX, a newly discovered mitochondrial Na(+)/Ca(2+) exchanger, is expressed in astrocytes isolated from mice of either sex. Immunoblot analysis of organellar fractions showed that the location of NCLX is confined to mitochondria. Using pericam-based mitochondrial Ca(2+) imaging and NCLX inhibition either by siRNA or by the pharmacological blocker CGP37157, we demonstrated that NCLX is responsible for mitochondrial Ca(2+) extrusion. Suppression of NCLX function altered cytosolic Ca(2+) dynamics in astrocytes and this was mediated by a strong effect of NCLX activity on Ca(2+) influx via store-operated entry. Furthermore, Ca(2+) influx through the store-operated Ca(2+) entry triggered strong, whereas ER Ca(2+) release triggered only modest mitochondrial Ca(2+) transients, indicating that the functional cross talk between the plasma membrane and mitochondrial domains is particularly strong in astrocytes. Finally, silencing of NCLX expression significantly reduced Ca(2+)-dependent processes in astrocytes (i.e., exocytotic glutamate release, in vitro wound closure, and proliferation), whereas Ca(2+) wave propagation was not affected. Therefore, NCLX, by meditating astrocytic mitochondrial Na(+)/Ca(2+) exchange, links between mitochondria and plasma membrane Ca(2+) signaling, thereby modulating cytoplasmic Ca(2+) transients required to control a diverse array of astrocyte functions.
PMID: 23616530 [PubMed - in process]
Noise Suppression and Surplus Synchrony by Coincidence Detection.
PLoS Comput Biol. 2013 Apr;9(4):e1002904
Authors: Schultze-Kraft M, Diesmann M, Grün S, Helias M
The functional significance of correlations between action potentials of neurons is still a matter of vivid debate. In particular, it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to correlated spiking on a fine temporal scale between pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high input correlation, in the presence of synchrony, a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks.
PMID: 23592953 [PubMed - as supplied by publisher]
Intra-day signal instabilities affect decoding performance in an intracortical neural interface system.
J Neural Eng. 2013 Apr 10;10(3):036004
Authors: Perge JA, Homer ML, Malik WQ, Cash S, Eskandar E, Friehs G, Donoghue JP, Hochberg LR
Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional 'bias' in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. Significance. We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs.
PMID: 23574741 [PubMed - as supplied by publisher]
Direct Brain Control and Communication in Paralysis.
Brain Topogr. 2013 Mar 28;
Authors: Birbaumer N, Gallegos-Ayala G, Wildgruber M, Silvoni S, Soekadar SR
Despite considerable growth in the field of brain-computer or brain-machine interface (BCI/BMI) research reflected in several hundred publications each year, little progress was made to enable patients in complete locked-in state (CLIS) to reliably communicate using their brain activity. Independent of the invasiveness of the BCI systems tested, no sustained direct brain control and communication was demonstrated in a patient in CLIS so far. This suggested a more fundamental theoretical problem of learning and attention in brain communication with BCI/BMI, formulated in the extinction-of-thought hypothesis. While operant conditioning and goal-directed thinking seems impaired in complete paralysis, classical conditioning of brain responses might represent the only alternative. First experimental studies in CLIS using semantic conditioning support this assumption. Evidence that quality-of-life in locked-in-state is not as limited and poor as generally believed draise doubts that "patient wills" or "advanced directives"signed long-before the locked-in-state are useful. On the contrary, they might be used as an excuse to shorten anticipated long periods of care for these patients avoiding associated financial and social burdens. Current state and availability of BCI/BMI systems urge a broader societal discourse on the pressing ethical challenges associated with the advancements in neurotechnology and BCI/BMI research.
PMID: 23536247 [PubMed - as supplied by publisher]
Nicotine and clozapine cross-prime the locus coeruleus noradrenergic system to induce long-lasting potentiation in the rat hippocampus.
Hippocampus. 2013 Mar 20;
Authors: Rajkumar R, Suri S, Deng HM, Dawe GS
A priming-challenge schedule of nicotine treatment causes long-lasting potentiation (LLP), a form of synaptic plasticity closely associated with the norepinephrine (NE) neurotransmitter system, at the medial perforant path (MPP)-dentate gyrus (DG) synapse in the rat hippocampus. Previous reports revealed that nicotine activates the locus coeruleus (LC) noradrenergic (NAergic) system and this mechanism may underlie its beta-adrenoceptor sensitive LLP effects. Clozapine, an atypical antipsychotic, is also known to activate the LC. Interactions between nicotine and clozapine are of interest because of the prevalence of smoking in patients with schizophrenia and increasing interest in the use of nicotinic receptor ligands as cognitive enhancers. Rats were subchronically primed with nicotine, clozapine or saline. Twenty one to twenty eight days later, the effects of the nicotine, clozapine or saline challenge on the evoked field excitatory postsynaptic potentials (fEPSP) at the MPP-DG monosynaptic pathway were recorded as a measure of LLP. We confirmed the hypothesis that a challenge dose of either nicotine or clozapine induces LLP exclusively in nicotine- and clozapine-primed rats, and not in saline-primed rats, thus indicating a cross-priming effect. Moreover, unilateral suppression of LC using lidocaine abolished the LLP induced by nicotine in clozapine-primed rats. Furthermore, systemic treatment with clonidine (an ?2 adrenoceptor agonist that reduces NAergic activity via autoreceptors) prior to the challenge doses blocked the nicotine/clozapine-induced LLP in nicotine- and clozapine- primed rats. These findings may add to understanding of the cognitive enhancing effects of nicotine. © 2013 Wiley Periodicals, Inc.
PMID: 23520012 [PubMed - as supplied by publisher]