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Bionic Limbs: Clinical Reality and Academic Promises.
Sci Transl Med. 2014 Oct 8;6(257):257ps12
Authors: Farina D, Aszmann O
Three recent articles in Science Translational Medicine (Tan et al. and Ortiz-Catalan et al., this issue; Raspopovic et al., 5 Feb 2014 issue, 222ra19) present neuroprosthetic systems in which sensory information is delivered through direct nerve stimulation while controlling an action of the prosthesis-in all three cases, arm and hand movement. We discuss such sensory-motor integration and other key issues in prosthetic reconstruction, with an emphasis on the gap existing between clinically available systems and more advanced, custom-designed academic systems. In the near future, osseointegration, implanted muscle, and nerve electrodes for decoding and stimulation may be components of prosthetic systems for clinical use, available to a large patient population.
PMID: 25298319 [PubMed - as supplied by publisher]
Rare-Earth doped particles as dual-modality contrast agent for minimally-invasive luminescence and dual-wavelength photoacoustic imaging.
Sci Rep. 2014;4:6562
Authors: Sheng Y, Liao LD, Thakor N, Tan MC
Multi-modal imaging is an emerging area that integrates multiple imaging modalities to simultaneously capture visual information over many spatial scales. Complementary contrast agents need to be co-developed in order to achieve high resolution and contrast. In this work, we demonstrated that rare-earth doped particles (REDPs) can be employed as dual-modal imaging agents for both luminescence and photoacoustic (PA) imaging to achieve intrinsic high contrast, temporal and spatial resolution, reaching deeper depth. REDPs synthesized with different surfactants (citric acid, polyacrylic acid, ethylenediaminetetraacetic acid and sodium citrate) exhibit tunable emission properties and PA signal amplitudes. Amongst these samples, sodium citrate-modified REDPs showed the strongest PA signals. Furthermore, since REDPs have multiple absorption peaks, they offer a unique opportunity for multi-wavelength PA imaging (e.g. PA signals were measured using 520 and 975?nm excitations). The in vivo PA images around the cortical superior sagittal sinus (SSS) blood vessel captured with enhanced signal arising from REDPs demonstrated that in addition to be excellent luminescent probes, REDPs can also be used as successful PA contrast agents. Anisotropic polyacrylic acid-modified REDPs were found to be the best candidates for dual-modal luminescence and PA imaging due to their strong luminescence and PA signal intensities.
PMID: 25297843 [PubMed - in process]
Misdiagnosis as an ethical and scientific challenge.
Ann Ist Super Sanita. 2014;50(3):229-33
Authors: Farisco M, Petrini C
Difficulties of behavioral assessment of consciousness. An astonishingly high rate of misdiagnosis between vegetative state/unresponsive wakefulness syndrome and minimally conscious state has been detected. This raises the issue of the adequacy of the consciousness' assessment in patients with disorders of consciousness. The behavioral assessment of consciousness could be not able to detect covert awareness, which is increasingly identified by the instrumental assessment. Ancillary methods. Neurotechnology, particularly neuroimaging, provides relevant data concerning the neurological underlying condition of patients with DOCs, but the instrumental approach has still to assess some technical issues. Ethical considerations. A correct diagnosis of a DOC is not only an instrumental issue, but also an ethically relevant demand to the scientific community. Finally, an integration between behavioral and instrumental assessments seems to be the most adequate strategy in order to decrease the rate of misdiagnosis.
PMID: 25292270 [PubMed - in process]
Examining the role of the temporo-parietal network in memory, imagery, and viewpoint transformations.
Front Hum Neurosci. 2014;8:709
Authors: Dhindsa K, Drobinin V, King J, Hall GB, Burgess N, Becker S
The traditional view of the medial temporal lobe (MTL) focuses on its role in episodic memory. However, some of the underlying functions of the MTL can be ascertained from its wider role in supporting spatial cognition in concert with parietal and prefrontal regions. The MTL is strongly implicated in the formation of enduring allocentric representations (e.g., O'Keefe, 1976; King et al., 2002; Ekstrom et al., 2003). According to our BBB model (Byrne et al., 2007), these representations must interact with head-centered and body-centered representations in posterior parietal cortex via a transformation circuit involving retrosplenial areas. Egocentric sensory representations in parietal areas can then cue the recall of allocentric spatial representations in long-term memory and, conversely, the products of retrieval in MTL can generate mental imagery within a parietal "window." Such imagery is necessarily egocentric and forms part of visuospatial working memory, in which it can be manipulated for the purpose of planning/imagining the future. Recent fMRI evidence (Lambrey et al., 2012; Zhang et al., 2012) supports the BBB model. To further test the model, we had participants learn the locations of objects in a virtual scene and tested their spatial memory under conditions that impose varying demands on the transformation circuit. We analyzed how brain activity correlated with accuracy in judging the direction of an object (1) from visuospatial working memory (we assume transient working memory due to the order of tasks and the absence of change in viewpoint, but long-term memory retrieval is also possible), (2) after a rotation of viewpoint, or (3) after a rotation and translation of viewpoint (judgment of relative direction). We found performance-related activity in both tasks requiring viewpoint rotation (ROT and JRD, i.e., conditions 2 and 3) in the core medial temporal to medial parietal circuit identified by the BBB model. These results are consistent with the predictions of the BBB model, and shed further light on the neural mechanisms underlying spatial memory, mental imagery and viewpoint transformations.
PMID: 25278860 [PubMed]
Human stretch reflex pathways reexamined.
J Neurophysiol. 2014 Feb;111(3):602-12
Authors: Yavuz SU, Mrachacz-Kersting N, Sebik O, Berna Ünver M, Farina D, Türker KS
Reflex responses of tibialis anterior motor units to stretch stimuli were investigated in human subjects. Three types of stretch stimuli were applied (tap-like, ramp-and-hold, and half-sine stretch). Stimulus-induced responses in single motor units were analyzed using the classical technique, which involved building average surface electromyogram (SEMG) and peristimulus time histograms (PSTH) from the discharge times of motor units and peristimulus frequencygrams (PSF) from the instantaneous discharge rates of single motor units. With the use of SEMG and PSTH, the tap-like stretch stimulus induced five separate reflex responses, on average. With the same single motor unit data, the PSF technique indicated that the tap stimulus induced only three reflex responses. Similar to the finding using the tap-like stretch stimuli, ramp-and-hold stimuli induced several peaks and troughs in the SEMG and PSTH. The PSF analyses displayed genuine increases in discharge rates underlying the peaks but not underlying the troughs. Half-sine stretch stimuli induced a long-lasting excitation followed by a long-lasting silent period in SEMG and PSTH. The increase in the discharge rate, however, lasted for the entire duration of the stimulus and continued during the silent period. The results are discussed in the light of the fact that the discharge rate of a motoneuron has a strong positive linear association with the effective synaptic current it receives and hence represents changes in the membrane potential more directly and accurately than the other indirect measures. This study suggests that the neuronal pathway of the human stretch reflex does not include inhibitory pathways.
PMID: 24225537 [PubMed - indexed for MEDLINE]
Functional Specialization and Flexibility in Human Association Cortex.
Cereb Cortex. 2014 Sep 23;
Authors: Yeo BT, Krienen FM, Eickhoff SB, Yaakub SN, Fox PT, Buckner RL, Asplund CL, Chee MW
The association cortex supports cognitive functions enabling flexible behavior. Here, we explored the organization of human association cortex by mathematically formalizing the notion that a behavioral task engages multiple cognitive components, which are in turn supported by multiple overlapping brain regions. Application of the model to a large data set of neuroimaging experiments (N = 10 449) identified complex zones of frontal and parietal regions that ranged from being highly specialized to highly flexible. The network organization of the specialized and flexible regions was explored with an independent resting-state fMRI data set (N = 1000). Cortical regions specialized for the same components were strongly coupled, suggesting that components function as partially isolated networks. Functionally flexible regions participated in multiple components to different degrees. This heterogeneous selectivity was predicted by the connectivity between flexible and specialized regions. Functionally flexible regions might support binding or integrating specialized brain networks that, in turn, contribute to the ability to execute multiple and varied tasks.
PMID: 25249407 [PubMed - as supplied by publisher]
Serotonergic Modulation of Intrinsic Functional Connectivity.
Curr Biol. 2014 Sep 16;
Authors: Schaefer A, Burmann I, Regenthal R, Arélin K, Barth C, Pampel A, Villringer A, Margulies DS, Sacher J
Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood . Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation [2-4]. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.
PMID: 25242032 [PubMed - as supplied by publisher]
Optimizing the regularization for image reconstruction of cerebral diffuse optical tomography.
J Biomed Opt. 2014 Sep 1;19(9):96006
Authors: Habermehl C, Steinbrink J, Müller KR, Haufe S
PMID: 25208243 [PubMed - as supplied by publisher]
SPoC: a novel framework for relating the amplitude of neuronal oscillations to behaviorally relevant parameters.
Neuroimage. 2014 Feb 1;86:111-22
Authors: Dähne S, Meinecke FC, Haufe S, Höhne J, Tangermann M, Müller KR, Nikulin VV
Previously, modulations in power of neuronal oscillations have been functionally linked to sensory, motor and cognitive operations. Such links are commonly established by relating the power modulations to specific target variables such as reaction times or task ratings. Consequently, the resulting spatio-spectral representation is subjected to neurophysiological interpretation. As an alternative, independent component analysis (ICA) or alternative decomposition methods can be applied and the power of the components may be related to the target variable. In this paper we show that these standard approaches are suboptimal as the first does not take into account the superposition of many sources due to volume conduction, while the second is unable to exploit available information about the target variable. To improve upon these approaches we introduce a novel (supervised) source separation framework called Source Power Comodulation (SPoC). SPoC makes use of the target variable in the decomposition process in order to give preference to components whose power comodulates with the target variable. We present two algorithms that implement the SPoC approach. Using simulations with a realistic head model, we show that the SPoC algorithms are able extract neuronal components exhibiting high correlation of power with the target variable. In this task, the SPoC algorithms outperform other commonly used techniques that are based on the sensor data or ICA approaches. Furthermore, using real electroencephalography (EEG) recordings during an auditory steady state paradigm, we demonstrate the utility of the SPoC algorithms by extracting neuronal components exhibiting high correlation of power with the intensity of the auditory input. Taking into account the results of the simulations and real EEG recordings, we conclude that SPoC represents an adequate approach for the optimal extraction of neuronal components showing coupling of power with continuously changing behaviorally relevant parameters.
PMID: 23954727 [PubMed - indexed for MEDLINE]
Reconfigurable task-dependent functional coupling modes cluster around a core functional architecture.
Philos Trans R Soc Lond B Biol Sci. 2014 Oct 5;369(1653)
Authors: Krienen FM, Yeo BT, Buckner RL
Functional coupling across distributed brain regions varies across task contexts, yet there are stable features. To better understand the range and central tendencies of network configurations, coupling patterns were explored using functional MRI (fMRI) across 14 distinct continuously performed task states ranging from passive fixation to increasingly demanding classification tasks. Mean global correlation profiles across the cortex ranged from 0.69 to 0.82 between task states. Network configurations from both passive fixation and classification tasks similarly predicted task coactivation patterns estimated from meta-analysis of the literature. Thus, even across markedly different task states, central tendencies dominate the coupling configurations. Beyond these shared components, distinct task states displayed significant differences in coupling patterns in response to their varied demands. One possibility is that anatomical connectivity provides constraints that act as attractors pulling network configurations towards a limited number of robust states. Reconfigurable coupling modes emerge as significant modifications to a core functional architecture.
PMID: 25180304 [PubMed - in process]
Recording human cortical population spikes non-invasively - an EEG tutorial.
J Neurosci Methods. 2014 Aug 26;
Authors: Waterstraat G, Fedele T, Burghoff M, Scheer HJ, Curio G
BACKGROUND: Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis.
METHODS: The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online.
RESULTS: Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('?-bursts') can be studied in single-trials. Additionally, spatial filters obtained by Canonical Correlation Average regression (CCAr) increase the signal-to-noise ratio of components at about 1 kHz ('?-bursts') enabling their detection in non-invasive surface EEG.
CONCLUSIONS: sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses.
PMID: 25172805 [PubMed - as supplied by publisher]
Motor Imagery for Severely Motor-Impaired Patients: Evidence for Brain-Computer Interfacing as Superior Control Solution.
PLoS One. 2014;9(8):e104854
Authors: Höhne J, Holz E, Staiger-Sälzer P, Müller KR, Kübler A, Tangermann M
Brain-Computer Interfaces (BCIs) strive to decode brain signals into control commands for severely handicapped people with no means of muscular control. These potential users of noninvasive BCIs display a large range of physical and mental conditions. Prior studies have shown the general applicability of BCI with patients, with the conflict of either using many training sessions or studying only moderately restricted patients. We present a BCI system designed to establish external control for severely motor-impaired patients within a very short time. Within only six experimental sessions, three out of four patients were able to gain significant control over the BCI, which was based on motor imagery or attempted execution. For the most affected patient, we found evidence that the BCI could outperform the best assistive technology (AT) of the patient in terms of control accuracy, reaction time and information transfer rate. We credit this success to the applied user-centered design approach and to a highly flexible technical setup. State-of-the art machine learning methods allowed the exploitation and combination of multiple relevant features contained in the EEG, which rapidly enabled the patients to gain substantial BCI control. Thus, we could show the feasibility of a flexible and tailorable BCI application in severely disabled users. This can be considered a significant success for two reasons: Firstly, the results were obtained within a short period of time, matching the tight clinical requirements. Secondly, the participating patients showed, compared to most other studies, very severe communication deficits. They were dependent on everyday use of AT and two patients were in a locked-in state. For the most affected patient a reliable communication was rarely possible with existing AT.
PMID: 25162231 [PubMed - as supplied by publisher]
Ethical Issues in Neuromarketing: "I Consume, Therefore I am!"
Sci Eng Ethics. 2014 Aug 24;
Authors: Ulman YI, Cakar T, Yildiz G
Neuromarketing is a recent interdisciplinary field which crosses traditional boundaries between neuroscience, neuroeconomics and marketing research. Since this nascent field is primarily concerned with improving marketing strategies and promoting sales, there has been an increasing public aversion and protest against it. These protests can be exemplified by the reactions observed lately in Baylor School of Medicine and Emory University in the United States. The most recent attempt to stop ongoing neuromarketing research in France is also remarkable. The pertaining ethical issues have been continuously attracting much attention, especially since the number of neuromarketing companies has exceeded 300 world-wide. This paper begins with a brief introduction to the field of neurotechnology by presenting its current capabilities and limitations. Then, it will focus on the ethical issues and debates most related with the recent applications of this technology. The French Parliament's revision of rules on bioethics in 2004 has an exemplary role in our discussion. The proposal by Murphy et al. (2008) has attracted attention to the necessity of ethical codes structuring this field. A code has recently been declared by the Neuromarketing Science and Business Association. In this paper, it is argued that these technologies should be sufficiently discussed in public spheres and its use on humans should be fully carried out according to the ethical principles and legal regulations designed in line with human rights and human dignity. There is an urgent need in the interdisciplinary scientific bodies like ethics committees monitoring the research regarding the scientific and ethical values of nonmaleficence, beneficence, autonomy, confidentiality, right to privacy and protection of vulnerable groups.
PMID: 25150848 [PubMed - as supplied by publisher]
Externalization of Consciousness. Scientific Possibilities and Clinical Implications.
Curr Top Behav Neurosci. 2014 Aug 22;
Authors: Farisco M, Laureys S, Evers K
The paper starts by analyzing recent advancements in neurotechnological assessment of residual consciousnessConsciousness in patients with disorders of consciousnessDisorders of consciousness and in neurotechnology-mediated communication with them. Ethical issues arising from these developments are described, with particular focus on informed consent. Against this background, we argue for the necessity of further scientific efforts and ethical reflection in neurotechnological assessment of consciousness and 'cerebral communication' with verbally non-communicative patients.
PMID: 25146416 [PubMed - as supplied by publisher]
Visuo-motor coordination ability predicts performance with brain-computer interfaces controlled by modulation of sensorimotor rhythms (SMR).
Front Hum Neurosci. 2014;8:574
Authors: Hammer EM, Kaufmann T, Kleih SC, Blankertz B, Kübler A
Modulation of sensorimotor rhythms (SMR) was suggested as a control signal for brain-computer interfaces (BCI). Yet, there is a population of users estimated between 10 to 50% not able to achieve reliable control and only about 20% of users achieve high (80-100%) performance. Predicting performance prior to BCI use would facilitate selection of the most feasible system for an individual, thus constitute a practical benefit for the user, and increase our knowledge about the correlates of BCI control. In a recent study, we predicted SMR-BCI performance from psychological variables that were assessed prior to the BCI sessions and BCI control was supported with machine-learning techniques. We described two significant psychological predictors, namely the visuo-motor coordination ability and the ability to concentrate on the task. The purpose of the current study was to replicate these results thereby validating these predictors within a neurofeedback based SMR-BCI that involved no machine learning.Thirty-three healthy BCI novices participated in a calibration session and three further neurofeedback training sessions. Two variables were related with mean SMR-BCI performance: (1) a measure for the accuracy of fine motor skills, i.e., a trade for a person's visuo-motor control ability; and (2) subject's "attentional impulsivity". In a linear regression they accounted for almost 20% in variance of SMR-BCI performance, but predictor (1) failed significance. Nevertheless, on the basis of our prior regression model for sensorimotor control ability we could predict current SMR-BCI performance with an average prediction error of M = 12.07%. In more than 50% of the participants, the prediction error was smaller than 10%. Hence, psychological variables played a moderate role in predicting SMR-BCI performance in a neurofeedback approach that involved no machine learning. Future studies are needed to further consolidate (or reject) the present predictors.
PMID: 25147518 [PubMed]
A continuous-flow C. elegans sorting system with integrated optical fiber detection and laminar flow switching.
Lab Chip. 2014 Aug 20;
Authors: Yan Y, Ng LF, Ng LT, Choi KB, Gruber J, Bettiol AA, Thakor NV
We present a high-throughput continuous-flow C. elegans sorting device that works based on integrated optical fiber detection and laminar flow switching. Two types of genetically engineered nematodes are allowed to flow into the device and their genotypes are detected based on their fluorescence, without the need for immobilization, by integrated optical fibers. A novel dynamic fluidic switch sorts the nematodes to desired outlets. By changing input pressures of the control inlets, the laminar flow path is altered to steer the nematodes to appropriate outlets. Compared to previously reported microfluidic C. elegans sorting devices, sorting in this system is conducted in a continuous flow environment without any immobilization technique or need for multilayer mechanical valves to open and close the outlets. The continuous flow sorter not only increases the throughput but also avoids any kind of invasive or possibly damaging mechanical or chemical stimulus. We have characterized both the detection and the switching accuracy of the sorting device at different flow rates, and efficiencies approaching 100% can be achieved with a high throughput of about one nematode per second. To confirm that there was no significant damage to C. elegans following sorting, we recovered the sorted worms, finding no deaths and no differences in behavior and propagation compared to control.
PMID: 25140819 [PubMed - as supplied by publisher]
A bihemispheric autonomic model for traumatic stress effects on health and behavior.
Front Psychol. 2014;5:843
Authors: Lee SW, Gerdes L, Tegeler CL, Shaltout HA, Tegeler CH
A bihemispheric autonomic model (BHAM) may support advanced understanding of traumatic stress effects on physiology and behavior. The model builds on established data showing hemispheric lateralization in management of the autonomic nervous system, and proposes that traumatic stress can produce dominant asymmetry in activity of bilateral homologous brain regions responsible for autonomic management. Rightward and leftward dominant asymmetries are associated with sympathetic high arousal or parasympathetic freeze tendencies, respectively, and return to relative symmetry is associated with improved autonomic regulation. Autonomic auto-calibration for recovery (inverse of Jacksonian dissolution proposed by polyvagal theory) has implications for risk behaviors associated with traumatic life stress. Trauma-induced high arousal may be associated with risk for maladaptive behaviors to attenuate arousal (including abuse of alcohol or sedative-hypnotics). Trauma-induced freeze mode (including callous-unemotional trait) may be associated with low resting heart rate and risk for conduct disorders. The model may explain higher prevalence of leftward hemispheric abnormalities reported in studies of violence. Implications of the BHAM are illustrated through case examples of a military special operations officer with history of traumatic brain injury and post-traumatic stress disorder, and a university student with persisting post-concussion symptoms. Both undertook use of a noninvasive closed-loop neurotechnology - high-resolution, relational, resonance-based, electroencephalic mirroring - with ensuing decrease in hemispheric asymmetry, improvement in heart rate variability, and symptom reduction. Finally, the BHAM aligns with calls for researchers to use brain-behavioral constructs (research domain criteria or RDoC, proposed by the National Institutes of Mental Health) as building blocks for assessment and intervention in mental health science.
PMID: 25136325 [PubMed]
Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate.
Brain Res. 2014 Jan 16;1543:179-90
Authors: Lee LC, Rajkumar R, Dawe GS
The nucleus incertus (NI), a brainstem nucleus found in the pontine periventricular grey, is the primary source of the neuropeptide relaxin-3 in the mammalian brain. The NI neurons have also been previously reported to express several receptors and neurotransmitters, including corticotropin releasing hormone receptor 1 (CRF?) and gamma-aminobutyric acid (GABA). The NI projects widely to putative neural correlates of stress, anxiety, depression, feeding behaviour, arousal and cognition leading to speculation that it might be involved in several neuropsychiatric conditions. On the premise that relaxin-3 expressing neurons in the NI predominantly co-express CRF? receptors, a novel method for selective ablation of the rat brain NI neurons using corticotropin releasing factor (CRF)-saporin conjugate is described. In addition to a behavioural deficit in the fear conditioning paradigm, reverse transcriptase polymerase chain reaction (RT-PCR), western blotting (WB) and immunofluorescence labelling (IF) techniques were used to confirm the NI lesion. We observed a selective and significant loss of CRF? expressing cells, together with a consistent decrease in relaxin-3 and GAD65 expression. The significant ablation of relaxin-3 positive neurons of the NI achieved by this lesioning approach is a promising model to explore the neuropsychopharmacological implications of NI/relaxin-3 in behavioural neuroscience.
PMID: 24287211 [PubMed - indexed for MEDLINE]
Non-causal spike filtering improves decoding of movement intention for intracortical BCIs.
J Neurosci Methods. 2014 Aug 12;
Authors: Masse NY, Jarosiewicz B, Simeral JD, Bacher D, Stavisky SD, Cash SS, Oakley EM, Berhanu E, Eskandar E, Friehs G, Hochberg LR, Donoghue JP
BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically-recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials.
NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals.
RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study.
CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs.
PMID: 25128256 [PubMed - as supplied by publisher]
Computational and control methods in rehabilitation medicine.
Comput Math Methods Med. 2014;2014:707208
Authors: Cikajlo I, Watanabe T, Dosen S
PMID: 25126109 [PubMed - in process]
Lower-limb kinematics of single-leg squat performance in young adults.
Physiother Can. 2014;66(3):228-33
Authors: Horan SA, Watson SL, Carty CP, Sartori M, Weeks BK
PURPOSE: To determine the kinematic parameters that characterize good and poor single-leg squat (SLS) performance.
METHODS: A total of 22 healthy young adults free from musculoskeletal impairment were recruited for testing. For each SLS, both two-dimensional video and three-dimensional motion analysis data were collected. Pelvis, hip, and knee angles were calculated using a reliable and validated lower-limb (LL) biomechanical model. Two-dimensional video clips of SLSs were blindly assessed in random order by eight musculoskeletal physiotherapists using a 10-point ordinal scale. To facilitate between-group comparisons, SLS performances were stratified by tertiles corresponding to poor, intermediate, and good SLS performance.
RESULTS: Mean ratings of SLS performance assessed by physiotherapists were 8.3 (SD 0.5), 6.8 (SD 0.7), and 4.0 (SD 0.8) for good, intermediate, and poor squats, respectively. Three-dimensional analysis revealed that people whose SLS performance was assessed as poor exhibited increased hip adduction, reduced knee flexion, and increased medio-lateral displacement of the knee joint centre compared to those whose SLS performance was assessed as good (p?0.05).
CONCLUSIONS: Overall, poor SLS performance is characterized by inadequate knee flexion and excessive frontal plane motion of the knee and hip. Future investigations of SLS performance should consider standardizing knee flexion angle to illuminate other influential kinematic parameters.
PMID: 25125775 [PubMed]
Electrophysiology-based detection of emergency braking intention in real-world driving.
J Neural Eng. 2014 Aug 11;11(5):056011
Authors: Haufe S, Kim JW, Kim IH, Sonnleitner A, Schrauf M, Curio G, Blankertz B
Objective. The fact that all human action is preceded by brain processes partially observable through neuroimaging devices such as electroencephalography (EEG) is currently being explored in a number of applications. A recent study by Haufe et al (2011 J. Neural Eng. 8 056001) demonstrates the possibility of performing fast detection of forced emergency brakings during driving based on EEG and electromyography, and discusses the use of such neurotechnology for braking assistance systems. Since the study was conducted in a driving simulator, its significance regarding real-world applicability needs to be assessed. Approach. Here, we replicate that experimental paradigm in a real car on a non-public test track. Main results. Our results resemble those of the simulator study, both qualitatively (in terms of the neurophysiological phenomena observed and utilized) and quantitatively (in terms of the predictive improvement achievable using electrophysiology in addition to behavioral measures). Moreover, our findings are robust with respect to a temporary secondary auditory task mimicking verbal input from a fellow passenger. Significance. Our study serves as a real-world verification of the feasibility of electrophysiology-based detection of emergency braking intention as proposed in Haufe et al (2011 J. Neural Eng. 8 056001).
PMID: 25111850 [PubMed - as supplied by publisher]
Near-Infrared Light Responsive Multi-Compartmental Hydrogel Particles Synthesized Through Droplets Assembly Induced by Superhydrophobic Surface.
Small. 2014 Jul 24;
Authors: Luo R, Cao Y, Shi P, Chen CH
Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed.
PMID: 25059988 [PubMed - as supplied by publisher]
Neuronal Ensemble Synchrony during Human Focal Seizures.
J Neurosci. 2014 Jul 23;34(30):9927-44
Authors: Truccolo W, Ahmed OJ, Harrison MT, Eskandar EN, Cosgrove GR, Madsen JR, Blum AS, Potter NS, Hochberg LR, Cash SS
Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (?40-60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ?3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50-100 ms level. In addition, transient fine synchrony occurred primarily during the initial ?20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (?80 Hz) gamma-band and during high-frequency oscillations (?130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons.
PMID: 25057195 [PubMed - in process]
Dysfunctional Cortical Inhibition in Adult ADHD: Neural Correlates in Auditory Event-Related Potentials.
J Neurosci Methods. 2014 Jul 14;
Authors: Schubert JK, Gonzalez-Trejo E, Retz W, Rösler M, Corona-Strauss FI, Steidl G, Teuber T, Strauss DJ
In recent times, the relevance of an accurate diagnosis of attention-deficit/ hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.
PMID: 25033725 [PubMed - as supplied by publisher]
Decoding Vigilance with NIRS.
PLoS One. 2014;9(7):e101729
Authors: Bogler C, Mehnert J, Steinbrink J, Haynes JD
Sustained, long-term cognitive workload is associated with variations and decrements in performance. Such fluctuations in vigilance can be a risk factor especially during dangerous attention demanding activities. Functional MRI studies have shown that attentional performance is correlated with BOLD-signals, especially in parietal and prefrontal cortical regions. An interesting question is whether these BOLD-signals could be measured in real-world scenarios, say to warn in a dangerous workplace whenever a subjects' vigilance is low. Because fMRI lacks the mobility needed for such applications, we tested whether the monitoring of vigilance might be possible using Near-Infrared Spectroscopy (NIRS). NIRS is a highly mobile technique that measures hemodynamics in the surface of the brain. We demonstrate that non-invasive NIRS signals correlate with vigilance. These signals carry enough information to decode subjects' reaction times at a single trial level.
PMID: 25032963 [PubMed - as supplied by publisher]
Brain representations for acquiring and recalling visual-motor adaptations.
Neuroimage. 2014 Jul 11;
Authors: Bédard P, Sanes JN
Humans readily learn and remember new motor skills, a process that likely underlies adaptation to changing environments. During adaptation, the brain develops new sensory-motor relationships, and if consolidation occurs, a memory of the adaptation can be retained for extended periods. Considerable evidence exists that multiple brain circuits participate in acquiring new sensory-motor memories, though the networks engaged in recalling these and whether the same brain circuits participate in their formation and recall has less clarity. To address these issues, we assessed brain activation with functional MRI while young healthy adults learned and recalled new sensory-motor skills by adapting to world-view rotations of visual feedback that guided hand movements. We found cerebellar activation related to adaptation rate, likely reflecting changes related to overall adjustments to the visual rotation. A set of parietal and frontal regions, including inferior and superior parietal lobules, premotor area, supplementary motor area and primary somatosensory cortex, exhibited non-linear learning-related activation that peaked in the middle of the adaptation phase. Activation in some of these areas, including the inferior parietal lobule, intra-parietal sulcus and somatosensory cortex, likely reflected actual learning, since the activation correlated with learning after-effects. Lastly, we identified several structures having recall-related activation, including the anterior cingulate and the posterior putamen, since the activation correlated with recall efficacy. These findings demonstrate dynamic aspects of brain activation patterns related to formation and recall of a sensory-motor skill, such that non-overlapping brain regions participate in distinctive behavioral events.
PMID: 25019676 [PubMed - as supplied by publisher]
The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats.
Ther Hypothermia Temp Manag. 2014 Jul 14;
Authors: Bazley FA, Pashai N, Kerr CL, All AH
Local and general hypothermia are used to treat spinal cord injury (SCI), as well as other neurological traumas. While hypothermia is known to provide significant therapeutic benefits due to its neuroprotective nature, it is unclear how the treatment may affect healthy tissues or whether it may cause undesired temperature changes in areas of the body that are not the targets of treatment. We performed 2-hour moderate general hypothermia (32°C core) or local hypothermia (30°C spinal cord) on rats that had received either a moderate contusive SCI or laminectomy (control) while monitoring temperatures at three sites: the core, spinal cord, and cortex. First, we identified that injured rats that received general hypothermia exhibited larger temperature drops at the spinal cord (-3.65°C, 95% confidence intervals [CIs] -3.72, -3.58) and cortex (-3.64°C, CIs -3.73, -3.55) than uninjured rats (spinal cord: -3.17°C, CIs -3.24, -3.10; cortex: -3.26°C, CIs -3.34, -3.17). This was found due to elevated baseline temperatures in the injured group, which could be due to inflammation. Second, both general hypothermia and local hypothermia caused a significant reduction in the cortical temperature (-3.64°C and -1.18°C, respectively), although local hypothermia caused a significantly lower drop in cortical temperature than general hypothermia (p<0.001). Lastly, the rates of rewarming of the cord were not significantly different among the methods or injury groups that were tested; the mean rate of rewarming was 0.13±0.1°C/min. In conclusion, local hypothermia may be more suitable for longer durations of hypothermia treatment for SCI to reduce temperature changes in healthy tissues, including the cortex.
PMID: 25019643 [PubMed - as supplied by publisher]
Dimensionality reduction for the analysis of brain oscillations.
Neuroimage. 2014 Jul 5;
Authors: Haufe S, Dähne S, Nikulin VV
Neuronal oscillations were shown to be associated with perceptual, motor and cognitive brain operations. While complex spatio-temporal dynamics are a hallmark of neuronal oscillations, they also represent a formidable challenge for a proper extraction and quantifications of oscillatory activity with non-invasive recording techniques such as EEG and MEG. In order to facilitate the study of neuronal oscillations we present a general purpose pre-processing approach, which can be applied for a wide range of analyses including but not restricted to inverse modeling and multivariate single-trial classification. The idea is to use dimensionality reduction with spatio-spectral decomposition (SSD) instead of the commonly and almost exclusively used principal component analysis (PCA). The key advantage of SSD lies in selecting components explaining oscillations-related variance instead of just any variance as in the case of PCA. For the validation of SSD pre-processing we performed extensive simulations with different inverse modeling algorithms and signal-to-noise ratios. In all these simulations SSD invariably outperformed PCA often by a large margin. Moreover, using a database of multichannel EEG recordings from 80 subjects we show that pre-processing with SSD significantly increases the performance of single-trial classification of imagined movements, compared to the classification with PCA pre-processing or without any dimensionality reduction. Our simulations and analysis of real EEG experiments show that, while not being supervised, the SSD algorithm is capable of extracting components primarily relating to the signal of interest often using as little as 20 % of the data variance, instead of > 90 % variance as in case of PCA. Given its ease of use, absence of supervision, and capability to efficiently reduce the dimensionality of multivariate EEG/MEG data, we advocate the application of SSD pre-processing for the analysis of spontaneous and induced neuronal oscillations in normal subjects and patients.
PMID: 25003816 [PubMed - as supplied by publisher]
Manipulation of isolated brain nerve terminals by an external magnetic field using D-mannose-coated ?-Fe2O3 nano-sized particles and assessment of their effects on glutamate transport.
Beilstein J Nanotechnol. 2014;5:778-88
Authors: Borisova T, Krisanova N, Bor?sov A, Sivko R, Ostapchenko L, Babic M, Horak D
The manipulation of brain nerve terminals by an external magnetic field promises breakthroughs in nano-neurotechnology. D-Mannose-coated superparamagnetic nanoparticles were synthesized by coprecipitation of Fe(II) and Fe(III) salts followed by oxidation with sodium hypochlorite and addition of D-mannose. Effects of D-mannose-coated superparamagnetic maghemite (?-Fe2O3) nanoparticles on key characteristics of the glutamatergic neurotransmission were analysed. Using radiolabeled L-[(14)C]glutamate, it was shown that D-mannose-coated ?-Fe2O3 nanoparticles did not affect high-affinity Na(+)-dependent uptake, tonic release and the extracellular level of L-[(14)C]glutamate in isolated rat brain nerve terminals (synaptosomes). Also, the membrane potential of synaptosomes and acidification of synaptic vesicles was not changed as a result of the application of D-mannose-coated ?-Fe2O3 nanoparticles. This was demonstrated with the potential-sensitive fluorescent dye rhodamine 6G and the pH-sensitive dye acridine orange. The study also focused on the analysis of the potential use of these nanoparticles for manipulation of nerve terminals by an external magnetic field. It was shown that more than 84.3 ± 5.0% of L-[(14)C]glutamate-loaded synaptosomes (1 mg of protein/mL) incubated for 5 min with D-mannose-coated ?-Fe2O3 nanoparticles (250 µg/mL) moved to an area, in which the magnet (250 mT, gradient 5.5 ?/m) was applied compared to 33.5 ± 3.0% of the control and 48.6 ± 3.0% of samples that were treated with uncoated nanoparticles. Therefore, isolated brain nerve terminals can be easily manipulated by an external magnetic field using D-mannose-coated ?-Fe2O3 nanoparticles, while the key characteristics of glutamatergic neurotransmission are not affected. In other words, functionally active synaptosomes labeled with D-mannose-coated ?-Fe2O3 nanoparticles were obtained.
PMID: 24991515 [PubMed]