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  • Journal article
    Sollini J, Chadderton P, 2016,

    Comodulation enhances signal detection via priming of auditory cortical circuits

    , Journal of Neuroscience, Vol: 36, Pages: 12299-12311, ISSN: 0270-6474

    Acoustic environments are composed of complex overlapping sounds that the auditory system is required to segregate into discrete perceptual objects. The functions of distinct auditory processing stations in this challenging task are poorly understood. Here we show a direct role for mouse auditory cortex in detection and segregation of acoustic information. We measured the sensitivity of auditory cortical neurons to brief tones embedded in masking noise. By altering spectrotemporal characteristics of the masker, we reveal that sensitivity to pure tone stimuli is strongly enhanced in coherently modulated broadband noise, corresponding to the psychoacoustic phenomenon comodulation masking release. Improvements in detection were largest following priming periods of noise alone, indicating that cortical segregation is enhanced over time. Transient opsin-mediated silencing of auditory cortex during the priming period almost completely abolished these improvements, suggesting that cortical processing may play a direct and significant role in detection of quiet sounds in noisy environments.

  • Journal article
    Datta G, Violante IR, Scott G, Zimmerman K, Santos-Ribeiro A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Matthews PMet al., 2016,

    Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis.

    , Multiple Sclerosis, Vol: 23, Pages: 1469-1478, ISSN: 1352-4585

    BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied. TSPO PET imaging with [(11)C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). RESULTS: [(11)C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [(11)C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [(11)C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [(11)C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. CONCLUSION: MRS [ myo-inositol] and PET [(11)C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [(11)C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.

  • Journal article
    Makin T, de Vignemont F, Faisal AA,

    Neurocognitive considerations to the embodiment of technology

    , Nature Biomedical Engineering, ISSN: 2157-846X

    By exploiting robotics and information technology, teams of biomedical engineers are enhancing human sensory and motor abilities. Such augmentation technology ― to be worn, implanted or ingested ― aims to both restore and improve existing human capabilities (such as faster running, via exoskeletons), and to add new ones (for example, a ‘radar sense’). The development of augmentation technology is driven by rapid advances in human–machine interfaces, energy storage and mobile computing. Although engineers are embracing body augmentation from a technical perspective, little attention has been devoted to how the human brain might support such technological innovation. In this Comment, we highlight expected neurocognitive bottlenecks imposed by brain plasticity, adaptation and learning that could impact the design and performance of sensory and motor augmentation technology. We call for further consideration of how human–machine integration can be best achieved.

  • Conference paper
    Li L, Violante I, Ross E, Leech R, Hampshire A, Carmichael D, Sharp Det al., 2016,


    , Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
  • Journal article
    Newbould R, Muraro P, Bishop C, Waldman Aet al., 2016,

    Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions

    , NeuroImage-Clinical, Vol: 13, Pages: 9-15, ISSN: 2213-1582

    Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between “younger” and “older” onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses.21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors.Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group.These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.

  • Journal article
    Wisden W, Uygun DS, Ye Z, Zecharia AY, Harding EC, Yu X, Yustos R, Vyssotski AL, Brickley SG, Franks NPet al., 2016,

    Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons

    , Journal of Neuroscience, Vol: 36, Pages: 11171-11184, ISSN: 0270-6474

    Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep.

  • Journal article
    Badura A, Clopath C, Schonewille M, De Zeeuw CIet al., 2016,

    Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    , Scientific Reports, Vol: 6, ISSN: 2045-2322

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.

  • Journal article
    Leppa E, Linden A-M, Aller MI, Wulff P, Vekovischeva O, Luscher B, Lueddens H, Wisden W, Korpi ERet al., 2016,

    Increased motor-impairing effects of the neuroactive steroid sregnanolone in mice with targeted inactivation of the GABA(A) seceptor gamma 2 subunit in the cerebellum

    , Frontiers in Pharmacology, Vol: 7, ISSN: 1663-9812

    Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABAA receptors. In recombinant receptors and genetic mouse models their actions depend on the α, β, and δ subunits of the receptor, especially on those that form extrasynaptic GABAA receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched γ2 subunit-containing receptors and even on αβ binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5β-pregnan-3α-ol-20-one is altered in genetically engineered mouse models that have deficient GABAA receptor-mediated synaptic inhibition in selected neuronal populations. Mouse lines with the GABAA receptor γ2 subunit gene selectively deleted either in parvalbumin-containing cells (including cerebellar Purkinje cells), cerebellar granule cells, or just in cerebellar Purkinje cells were trained on the accelerated rotating rod and then tested for motor impairment after cumulative intraperitoneal dosing of 5β-pregnan-3α-ol-20-one. Motor-impairing effects of 5β-pregnan-3α-ol-20-one were strongly increased in all three mouse models in which γ2 subunit-dependent synaptic GABAA responses in cerebellar neurons were genetically abolished. Furthermore, rescue of postsynaptic GABAA receptors in Purkinje cells normalized the effect of the steroid. Anxiolytic/explorative effects of the steroid in elevated plus maze and light:dark exploration tests in mice with Purkinje cell γ2 subunit inactivation were similar to those in control mice. The results suggest that, when the deletion of γ2 subunit has removed synaptic GABAA receptors from the specific cerebellar neuronal populations, the effects of neuroactive steroids solely on extrasynaptic αβ or αβδ receptors lead to enhanced changes in the cerebellum-generated behavior.

  • Journal article
    Wilson C, Munoz-Palma E, Henriquez DR, Palmisano I, Tulio Nunez M, Di Giovanni S, Gonzalez-Billault Cet al., 2016,

    A Feed-Forward Mechanism Involving the NOX Complex and RyR-Mediated Ca2+ Release During Axonal Specification

    , Journal of Neuroscience, Vol: 36, Pages: 11107-11119, ISSN: 1529-2401

    Physiological levels of ROS support neurite outgrowth and axonal specification, but the mechanisms by which ROS are able to shapeneurons remain unknown. Ca 2, a broad intracellular second messenger, promotes both Rac1 activation and neurite extension. Ca 2releasefromthe endoplasmic reticulum, mediated by boththe IP3R1 and ryanodine receptor (RyR) channels, requires physiological ROSlevels that are mainly sustained by the NADPH oxidase (NOX) complex. In this work, we explore the contribution of the link betweenNOX and RyR-mediated Ca 2 release toward axonal specification of rat hippocampal neurons. Using genetic approaches, we findthatNOX activation promotes both axonal development and Rac1 activationthrough a RyR-mediatedmechanism,whichinturn activatesNOX through Rac1, one of the NOX subunits. Collectively, these data suggest a feedforward mechanism that integrates both NOX activityand RyR-mediated Ca 2 release to support cellular mechanisms involved in axon development.

  • Journal article
    Stango A, Yazdandoost KY, Negro F, Farina Det al., 2016,

    Characterization of in-body to on-body wireless radio frequency link for upper limb prostheses.

    , PLOS One, Vol: 11, ISSN: 1932-6203

    Wireless implanted devices can be used to interface patients with disabilities with the aim of restoring impaired motor functions. Implanted devices that record and transmit electromyographic (EMG) signals have been applied for the control of active prostheses. This simulation study investigates the propagation losses and the absorption rate of a wireless radio frequency link for in-to-on body communication in the medical implant communication service (MICS) frequency band to control myoelectric upper limb prostheses. The implanted antenna is selected and a suitable external antenna is designed. The characterization of both antennas is done by numerical simulations. A heterogeneous 3D body model and a 3D electromagnetic solver have been used to model the path loss and to characterize the specific absorption rate (SAR). The path loss parameters were extracted and the SAR was characterized, verifying the compliance with the guideline limits. The path loss model has been also used for a preliminary link budget analysis to determine the feasibility of such system compliant with the IEEE 802.15.6 standard. The resulting link margin of 11 dB confirms the feasibility of the system proposed.

  • Conference paper
    Patrick KCA, Imtiaz SA, Bowyer S, Rodriguez Villegas Eet al., 2016,

    An Algorithm for Automatic Detection of Drowsiness for Use inWearable EEG Systems

    , IEEE EMBC 2016, Publisher: IEEE, ISSN: 1557-170X

    Lack of proper restorative sleep can induce sleepinessat odd hours making a person drowsy. This onset of drowsinesscan be detrimental for the individual in a number of waysif it happens at an unwanted time. For example, drowsinesswhile driving a vehicle or operating heavy machinery poses athreat to the safety and wellbeing of individuals as well as thosearound them. Timely detection of drowsiness can prevent theoccurrence of unfortunate accidents thereby improving roadand work environment safety. In this paper, by analyzing theelectroencephalographic (EEG) signals of human subjects inthe frequency domain, several features across different EEGchannels are explored. Of these, three features are identified tohave a strong correlation with drowsiness. A weighted sum ofthese defining features, extracted from a single EEG channel,is then used with a simple classifier to automatically separatethe state of wakefulness from drowsiness. The proposed algorithmresulted in drowsiness detection sensitivity of 85% andspecificity of 93%.

  • Journal article
    De Marcellis A, Palange E, Nubile L, Faccio M, Di Patrizio Stanchieri G, Constandinou Tet al., 2016,

    A pulsed coding technique based on optical UWB modulation for high data rate low power wireless implantable biotelemetry

    , Electronics, Vol: 5, Pages: 1-10, ISSN: 2079-9292

    This paper reports on a pulsed coding technique based on optical Ultra-wideband (UWB)modulation for wireless implantable biotelemetry systems allowing for high data rate link whilstenabling significant power reduction compared to the state-of-the-art. This optical data codingapproach is suitable for emerging biomedical applications like transcutaneous neural wirelesscommunication systems. The overall architecture implementing this optical modulation techniqueemploys sub-nanosecond pulsed laser as the data transmitter and small sensitive area photodiode asthe data receiver. Moreover, it includes coding and decoding digital systems, biasing and drivinganalogue circuits for laser pulse generation and photodiode signal conditioning. The complete systemhas been implemented on Field-Programmable Gate Array (FPGA) and prototype Printed CircuitBoard (PCB) with discrete off-the-shelf components. By inserting a diffuser between the transmitterand the receiver to emulate skin/tissue, the system is capable to achieve a 128 Mbps data rate with abit error rate less than 10 9 and an estimated total power consumption of about 5 mW correspondingto a power efficiency of 35.9 pJ/bit. These results could allow, for example, the transmission of an800-channel neural recording interface sampled at 16 kHz with 10-bit resolution.

  • Conference paper
    Castronovo AM, Mrachacz-Kersting N, Landi F, Jørgensen H, Severinsen K, Farina Det al., 2016,

    Motor Unit Coherence at Low Frequencies Increases Together with Cortical Excitability Following a Brain-Computer Interface Intervention in Acute Stroke Patients.

    , 3rd International Conference on NeuroRehabilitation (ICNR2016), Publisher: Springer, Pages: 1001-1005

    This study aims at investigating the neurophysiological correlates of increased cortical excitability following a Brain-Computer interface based intervention in three acute stroke survivors. The analysis was performed on high-density EMG signals recorded from the Tibialis Anterior muscle. All patients showed an increased excitability in the motor cortex area of interest following the BCI intervention. Moreover, coherence between motor unit spike trains increased in the frequency band 1–5 Hz, suggesting an increase in the common oscillatory drive to the target muscle.

  • Conference paper
    Mace M, Rinne P, Kinany N, Bentley P, Burdet Eet al., 2016,

    Collaborative gaming to enhance patient performance during virtual therapy

    , 3rd International Conference on NeuroRehabilitation (ICNR), Publisher: Springer International Publishing AG, Pages: 375-379, ISSN: 2195-3562

    We present a collaborative training game, based on a novel task where the participants are virtually but dynamically coupled and require collective actions for successful task completion. This can be considered a new type of interpersonal interaction which both increases player motivation during training (compared to single-player participation) and also intrinsically balances the skill levels of the two partners without the need for an additional procedure. This is achieved by a temporary averaging, during collaboration, of the individual performance’s which leads to a more balanced playing field and challenge point being set for both partners.

  • Journal article
    Aszmann OC, Vujaklija I, Roche AD, Salminger S, Herceg M, Sturma A, Hruby LA, Pittermann A, Hofer C, Amsuess S, Farina Det al., 2016,

    Elective amputation and bionic substitution restore functional hand use after critical soft tissue injuries

    , Scientific Reports, Vol: 6, ISSN: 2045-2322

    Critical soft tissue injuries may lead to a non-functional and insensate limb. In these cases standard reconstructive techniques will not suffice to provide a useful outcome, and solutions outside the biological arena must be considered and offered to these patients. We propose a concept which, after all reconstructive options have been exhausted, involves an elective amputation along with a bionic substitution, implementing an actuated prosthetic hand via a structured tech-neuro-rehabilitation program. Here, three patients are presented in whom this concept has been successfully applied after mutilating hand injuries. Clinical tests conducted before, during and after the procedure, evaluating both functional and psychometric parameters, document the benefits of this approach. Additionally, in one of the patients, we show the possibility of implementing a highly functional and natural control of an advanced prosthesis providing both proportional and simultaneous movements of the wrist and hand for completing tasks of daily living with substantially less compensatory movements compared to the traditional systems. It is concluded that the proposed procedure is a viable solution for re-gaining highly functional hand use following critical soft tissue injuries when existing surgical measures fail. Our results are clinically applicable and can be extended to institutions with similar resources.

  • Journal article
    Rinne P, Mace M, Nakornchai T, Zimmerman K, Fayer S, Sharma P, Liardon JL, Burdet E, Bentley Pet al., 2016,

    Democratizing Neurorehabilitation: How Accessible are Low-Cost Mobile-Gaming Technologies for Self-Rehabilitation of Arm Disability in Stroke?

    , PLOS One, Vol: 11, ISSN: 1932-6203

    Motor-training software on tablets or smartphones (Apps) offer a low-cost, widely-available solution to supplement arm physiotherapy after stroke. We assessed the proportions of hemiplegic stroke patients who, with their plegic hand, could meaningfully engage with mobile-gaming devices using a range of standard control-methods, as well as by using a novel wireless grip-controller, adapted for neurodisability. We screened all newly-diagnosed hemiplegic stroke patients presenting to a stroke centre over 6 months. Subjects were compared on their ability to control a tablet or smartphone cursor using: finger-swipe, tap, joystick, screen-tilt, and an adapted handgrip. Cursor control was graded as: no movement (0); less than full-range movement (1); full-range movement (2); directed movement (3). In total, we screened 345 patients, of which 87 satisfied recruitment criteria and completed testing. The commonest reason for exclusion was cognitive impairment. Using conventional controls, the proportion of patients able to direct cursor movement was 38-48%; and to move it full-range was 55-67% (controller comparison: p>0.1). By comparison, handgrip enabled directed control in 75%, and full-range movement in 93% (controller comparison: p<0.001). This difference between controllers was most apparent amongst severely-disabled subjects, with 0% achieving directed or full-range control with conventional controls, compared to 58% and 83% achieving these two levels of movement, respectively, with handgrip. In conclusion, hand, or arm, training Apps played on conventional mobile devices are likely to be accessible only to mildly-disabled stroke patients. Technological adaptations such as grip-control can enable more severely affected subjects to engage with self-training software.

  • Journal article
    Looney D, Goverdovsky V, Rosenzweig I, Morrell MJ, Mandic DPet al., 2016,

    A Wearable In-Ear Encephalography Sensor for Monitoring Sleep: Preliminary Observations from Nap Studies

    , Annals of the American Thoracic Society, Vol: 13, Pages: 2229-2233, ISSN: 2329-6933

    RATIONALE: To date the only quantifiable measure of neural changes that define sleep is electroencephalography (EEG). Although widely used for clinical testing, scalp-electrode EEG is costly and poorly tolerated by sleeping patients. OBJECTIVES: This is a pilot study to assess the agreement between EEG recordings obtained from a new ear-EEG sensor and those obtained simultaneously from standard scalp electrodes. METHODS: Participants were 4 healthy men, ages 25 to 36 years. During naps, EEG tracings were recorded simultaneously from the ear sensor and standard scalp electrodes. A clinical expert, blinded to the data collection, analyzed 30-second epochs of recordings from both devices using standardized criteria. The agreement between scalp- and ear-recordings was assessed. MEASUREMENTS AND MAIN RESULTS: We scored 360 epochs (scalp-EEG and ear-EEG) of which 254 (70.6%) were scored as non-rapid-eye movement (NREM) sleep using scalp-EEG. The ear-EEG sensor had a sensitivity of 0.88 (95% CI 0.82 to 0.92) and specificity of 0.78 (95% CI 0.70 to 0.84) in detecting N2/N3 sleep. The kappa coefficient, between the scalp- and ear-EEG, was 0.65 (95% CI 0.58 to 0.73). As a sleep monitor (all NREM sleep stages versus wake), the in-ear sensor had a sensitivity of 0.91 (95% CI 0.87 to 0.94) and specificity of 0.66 (95% CI 0.56 to 0.75). The kappa coefficient was 0.60 (95% CI 0.50 to 0.69). CONCLUSIONS: Substantial agreement was observed between recordings derived from a new ear-EEG sensor and conventional scalp electrodes on 4 healthy volunteers during daytime naps.

  • Journal article
    Schultz SR, Copeland CS, Foust AJ, Quicke P, Schuck Ret al., 2016,

    Advances in two-photon scanning and scanless microscopy technologies for functional neural circuit imaging

    , Proceedings of the IEEE, Vol: 105, Pages: 139-157, ISSN: 0018-9219

    Recent years have seen substantial developments in technology for imaging neural circuits, raising the prospect of large-scale imaging studies of neural populations involved in information processing, with the potential to lead to step changes in our understanding of brain function and dysfunction. In this paper, we will review some key recent advances: improved fluorophores for single-cell resolution functional neuroimaging using a two-photon microscope; improved approaches to the problem of scanning active circuits; and the prospect of scanless microscopes which overcome some of the bandwidth limitations of current imaging techniques. These advances in technology for experimental neuroscience have in themselves led to technical challenges, such as the need for the development of novel signal processing and data analysis tools in order to make the most of the new experimental tools. We review recent work in some active topics, such as region of interest segmentation algorithms capable of demixing overlapping signals, and new highly accurate algorithms for calcium transient detection. These advances motivate the development of new data analysis tools capable of dealing with spatial or spatiotemporal patterns of neural activity that scale well with pattern size.

  • Journal article
    Warren SC, Kim Y, Stone JM, Mitchell C, Knight JC, Neil MAA, Paterson C, French PMW, Dunsby CWet al., 2016,

    Adaptive multiphoton endomicroscopy through a dynamically deformed multicore optical fiber using proximal detection

    , Optics Express, Vol: 24, Pages: 21474-21484, ISSN: 1094-4087

    This paper demonstrates multiphoton excited fluorescenceimaging through a polarisation maintaining multicore fiber (PM-MCF)while the fiber is dynamically deformed using all-proximal detection.Single-shot proximal measurement of the relative optical path lengths of allthe cores of the PM-MCF in double pass is achieved using a Mach-Zehnderinterferometer read out by a scientific CMOS camera operating at 416 Hz.A non-linear least squares fitting procedure is then employed to determinethe deformation-induced lateral shift of the excitation spot at the distal tip ofthe PM-MCF. An experimental validation of this approach is presented thatcompares the proximally measured deformation-induced lateral shift infocal spot position to an independent distally measured ground truth. Theproximal measurement of deformation-induced shift in focal spot position isapplied to correct for deformation-induced shifts in focal spot positionduring raster-scanning multiphoton excited fluorescence imaging.

  • Journal article
    Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Bartsch AJ, Jbabdi S, Sotiropoulos SN, Andersson JL, Griffanti L, Douaud G, Okell TW, Weale P, Dragonu I, Garratt S, Hudson S, Collins R, Jenkinson M, Matthews PM, Smith SMet al., 2016,

    Multimodal population brain imaging in the UK Biobank prospective epidemiological study

    , Nature Neuroscience, Vol: 19, Pages: 1523-1536, ISSN: 1546-1726

    Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank.

  • Software
    Goodman DFM, Stimberg M, Brette R, 2016,

    Brian 2.0 simulator

    Brian is a simulator for spiking neural networks. It is written in the Python programming language and is available on almost all platforms. We believe that a simulator should not only save the time of processors, but also the time of scientists. Brian is therefore designed to be easy to learn and use, highly flexible and easily extensible.

  • Journal article
    Imtiaz SA, Mardell JAMES, Saremi-Yarahmadi SIAVASH, Rodriguez Villegas ESTHERet al., 2016,

    ECG Artefact Identification and Removal in mHealth Systems for Continuous Patient Monitoring

    , Healthcare Technology Letters, Vol: 3, Pages: 171-176, ISSN: 2053-3713

    Continuous patient monitoring systems acquire enormous amounts of data that is either manually analysed by doctors or automaticallyprocessed using intelligent algorithms. Sections of data acquired over long period of time can be corrupted with artefacts due to patientmovement, sensor placement and interference from other sources. Because of the large volume of data these artefacts need to be automaticallyidentified so that the analysis systems and doctors are aware of them while making medical diagnosis. This paper explores three importantfactors that must be considered and quantified for the design and evaluation of automatic artefact identification algorithms: signal quality,interpretation quality and computational complexity. The first two are useful to determine the effectiveness of an algorithm while the third isparticularly vital in mHealth systems where computational resources are heavily constrained. A series of artefact identification and filteringalgorithms are then presented focusing on the electrocardiography data. These algorithms are quantified using the three metrics to demonstratehow different algorithms can be evaluated and compared to select the best ones for a given wireless sensor network.

  • Journal article
    Patel GK, Dosen S, Castellini C, Farina Det al., 2016,

    Multichannel electrotactile feedback for simultaneous and proportional myoelectric control

    , Journal of Neural Engineering, Vol: 13, ISSN: 1741-2560

    © 2016 IOP Publishing Ltd. Objective. Closing the loop in myoelectric prostheses by providing artificial somatosensory feedback to the user is an important need for prosthetic users. Previous studies investigated feedback strategies in combination with the control of one degree of freedom of simple grippers. Modern hands, however, are sophisticated multifunction systems. In this study, we assessed multichannel electrotactile feedback integrated with an advanced method for the simultaneous and proportional control of individual fingers of a dexterous hand. Approach. The feedback used spatial and frequency coding to provide information on the finger positions (normalized flexion angles). A comprehensive set of conditions have been investigated in 28 able-bodied subjects, including feedback modalities (visual, electrotactile and no feedback), control tasks (fingers and grasps), systems (virtual and real hand), control methods (ideal and realistic) and range of motion (low and high). The task for the subjects was to operate the hand using closed-loop myoelectric control and generate the desired movement (e.g., selected finger or grasp at a specific level of closure). Main results. The subjects could perceive the multichannel and multivariable electrotactile feedback and effectively exploit it to improve the control performance with respect to open-loop grasping. The improvement however depended on the reliability of the feedforward control, with less consistent control exhibiting performance trends that were more complex across the conditions. Significance. The results are promising for the potential application of advanced feedback to close the control loop in sophisticated prosthetic systems.

  • Journal article
    Seemungal BM, Yousif N, Abou-El-Ela-Bourquin B, Fu R, Bhrugubanda V, Schultz SRet al., 2016,

    Dopamine activation preserves visual motion perception despite noise interference of human V5/MT

    , Journal of Neuroscience, Vol: 36, Pages: 9303-9312, ISSN: 1529-2401

    When processing sensory signals, the brain must account for noise, both noise in the stimulus and that arising from within its own neuronal circuitry. Dopamine receptor activation is known to enhance both visual cortical signal-to-noise-ratio (SNR) and visual perceptual performance; however, it is unknown whether these two dopamine-mediated phenomena are linked. To assess this, we used single-pulse transcranial magnetic stimulation (TMS) applied to visual cortical area V5/MT to reduce the SNR focally and thus disrupt visual motion discrimination performance to visual targets located in the same retinotopic space. The hypothesis that dopamine receptor activation enhances perceptual performance by improving cortical SNR predicts that dopamine activation should antagonize TMS disruption of visual perception. We assessed this hypothesis via a double-blinded, placebo-controlled study with the dopamine receptor agonists cabergoline (a D2 agonist) and pergolide (a D1/D2 agonist) administered in separate sessions (separated by 2 weeks) in 12 healthy volunteers in a William's balance-order design. TMS degraded visual motion perception when the evoked phosphene and the visual stimulus overlapped in time and space in the placebo and cabergoline conditions, but not in the pergolide condition. This suggests that dopamine D1 or combined D1 and D2 receptor activation enhances cortical SNR to boost perceptual performance. That local visual cortical excitability was unchanged across drug conditions suggests the involvement of long-range intracortical interactions in this D1 effect. Because increased internal noise (and thus lower SNR) can impair visual perceptual learning, improving visual cortical SNR via D1/D2 agonist therapy may be useful in boosting rehabilitation programs involving visual perceptual training.

  • Conference paper
    De Marcellis A, Palange E, Faccio M, Nubile L, Di Patrizio Stanchieri G, Constandinou TGet al., 2016,

    A new optical UWB modulation technique for 250Mbps wireless link in implantable biotelemetry systems

    , Eurosensors, Publisher: Elsevier: Creative Commons Attribution Non-Commercial No-Derivatives License, Pages: 1676-1680, ISSN: 1877-7058

    We propose a new UWB modulation technique for wireless optical communications in transcutaneous biotelemetry. The solution, based on the generation of sub-nanoseconds laser pulses, allows for a high data rate link whilst achieving a significant power reduction (energy per bit) compared to the state-ofthe- art. These features make this particularly suitable for emerging biomedical applications such as implantable neural/biosensor systems. The relatively simple architecture consists of a transmitter and receiver that can be integrated in a standard CMOS technology in a compact Silicon footprint (lower than 1mm^2 in a 0.18μm technology). These parts, optimised for low-voltage/low-power operation, include coding and decoding digital systems, biasing and driving analogue circuits for laser pulse generation and photodiode signal conditioning. Experimental findings with prototype PCBs have validated the new paradigm showing the system capabilities to achieve a BER less than 10^-9 with data rate up to 250Mbps and estimated total power consumption lower than 5mW.

  • Conference paper
    Peress L, Violante IR, Scott G, Zimmerman K, Sharp D, Nicholas R, Raffel Jet al., 2016,

    Thalamic magnetic resonance spectroscopy in highly active multiple sclerosis

    , 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 210-211, ISSN: 1352-4585
  • Conference paper
    Zhao H, Dehkhoda F, Ramezani R, Sokolov D, Constandinou TG, Liu Y, Degenaar Pet al., 2016,

    A CMOS-Based Neural Implantable Optrode for Optogenetic Stimulation and Electrical Recording

    , IEEE Biomedical Circuits and Systems (BioCAS) Conference, Publisher: IEEE, Pages: 286-289

    This paper presents a novel integrated optrode for simultaneous optical stimulation and electrical recording for closed -loop optogenetic neuro-prosthetic applications. The design has been implemented in a commercially available 0.35μm CMOS process. The system includes circuits for controlling the optical stimulations; recording local field potentials (LFPs); and onboard diagnostics. The neural interface has two clusters of stimulation and recording sites. Each stimulation site has a bonding point for connecting a micro light emitting diode (μLED) to deliver light to the targeted area of brain tissue. Each recording site is designed to be post-processed with electrode materials to provide monitoring ofneural activity. On-chip diagnostic sensing has been included to provide real-time diagnostics for post-implantation and during normal operation.

  • Journal article
    Schweisfurth MA, Markovic M, Dosen S, Teich F, Graimann B, Farina Det al., 2016,

    Electrotactile EMG feedback improves the control of prosthesis grasping force

    , Journal of Neural Engineering, Vol: 13, ISSN: 1741-2560

    © 2016 IOP Publishing Ltd. Objective. A drawback of active prostheses is that they detach the subject from the produced forces, thereby preventing direct mechanical feedback. This can be compensated by providing somatosensory feedback to the user through mechanical or electrical stimulation, which in turn may improve the utility, sense of embodiment, and thereby increase the acceptance rate. Approach. In this study, we compared a novel approach to closing the loop, namely EMG feedback (emgFB), to classic force feedback (forceFB), using electrotactile interface in a realistic task setup. Eleven intact-bodied subjects and one transradial amputee performed a routine grasping task while receiving emgFB or forceFB. The two feedback types were delivered through the same electrotactile interface, using a mixed spatial/frequency coding to transmit 8 discrete levels of the feedback variable. In emgFB, the stimulation transmitted the amplitude of the processed myoelectric signal generated by the subject (prosthesis input), and in forceFB the generated grasping force (prosthesis output). The task comprised 150 trials of routine grasping at six forces, randomly presented in blocks of five trials (same force). Interquartile range and changes in the absolute error (AE) distribution (magnitude and dispersion) with respect to the target level were used to assess precision and overall performance, respectively. Main results. Relative to forceFB, emgFB significantly improved the precision of myoelectric commands (min/max of the significant levels) for 23%/36% as well as the precision of force control for 12%/32%, in intact-bodied subjects. Also, the magnitude and dispersion of the AE distribution were reduced. The results were similar in the amputee, showing considerable improvements. Significance. Using emgFB, the subjects therefore decreased the uncertainty of the forward pathway. Since there is a correspondence between the EMG and force, where the former anticipates the latte

  • Journal article
    Torricelli D, Gonzalez J, Weckx M, Jiménez-Fabián R, Vanderborght B, Sartori M, Dosen S, Farina D, Lefeber D, Pons JLet al., 2016,

    Human-like compliant locomotion: state of the art of robotic implementations

    , Bioinspiration and Biomimetics, Vol: 11, ISSN: 1748-3182

    This review paper provides a synthetic yet critical overview of the key biomechanical principles of human bipedal walking and their current implementation in robotic platforms. We describe the functional role of human joints, addressing in particular the relevance of the compliant properties of the different degrees of freedom throughout the gait cycle. We focused on three basic functional units involved in locomotion, i.e. the ankle-foot complex, the knee, and the hip-pelvis complex, and their relevance to whole-body performance. We present an extensive review of the current implementations of these mechanisms into robotic platforms, discussing their potentialities and limitations from the functional and energetic perspectives. We specifically targeted humanoid robots, but also revised evidence from the field of lower-limb prosthetics, which presents innovative solutions still unexploited in the current humanoids. Finally, we identified the main critical aspects of the process of translating human principles into actual machines, providing a number of relevant challenges that should be addressed in future research.

  • Journal article
    Hammad SH, Kamavuako EN, Farina D, Jensen Wet al., 2016,

    Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced Hitting Task.

    , Neuromodulation, Vol: 19, Pages: 804-811

    OBJECTIVES: An invasive brain-computer interface (BCI) is a promising neurorehabilitation device for severely disabled patients. Although some systems have been shown to work well in restricted laboratory settings, their utility must be tested in less controlled, real-time environments. Our objective was to investigate whether a specific motor task could be reliably detected from multiunit intracortical signals from freely moving animals in a simulated, real-time setting. MATERIALS AND METHODS: Intracortical signals were first obtained from electrodes placed in the primary motor cortex of four rats that were trained to hit a retractable paddle (defined as a "Hit"). In the simulated real-time setting, the signal-to-noise-ratio was first increased by wavelet denoising. Action potentials were detected, and features were extracted (spike count, mean absolute values, entropy, and combination of these features) within pre-defined time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit." RESULTS: We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9% for the three window sizes, respectively) when the decision was made based on a combination of features rather than on a single feature. However, the duration of the window length was not statistically significant (p = 0.5). CONCLUSION: Our results showed the feasibility of detecting a motor task in real time in a less restricted environment compared to environments commonly applied within invasive BCI research, and they showed the feasibility of using information extracted from multiunit recordings, thereby avoiding the time-consuming and complex task of extracting and sorting single units.

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