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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]
Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy.
Biomed Eng Online. 2013;12:120
Authors: Liao LD, Orellana J, Liu YH, Lin YR, Vipin A, Thakor NV, Shen K, Wilder-Smith E
BACKGROUND: Vascular hemodynamics is central to the regulation of neuro-metabolism and plays important roles in peripheral nerves diseases and their prevention. However, at present there are only a few techniques capable of directly measuring peripheral nerve vascular hemodynamics.
METHOD: Here, we investigate the use of dark-field functional photoacoustic microscopy (fPAM) for intrinsic visualizing of the relative hemodynamics of the rat sciatic nerve in response to localized temperature modulation (i.e., cooling and rewarming).
RESULTS AND CONCLUSION: Our main results show that the relative functional total hemoglobin concentration (HbT) is more significantly correlated with localized temperature changes than the hemoglobin oxygen saturation (SO2) changes in the sciatic nerve. Our study also indicates that the relative HbT changes are better markers of neuronal activation than SO2 during nerve temperature changes. Our results show that fPAM is a promising candidate for in vivo imaging of peripheral nerve hemodynamics without the use of contrast agents. Additionally, this technique may shed light on the neuroprotective effect of hypothermia on peripheral nerves by visualizing their intrinsic hemodynamics.
PMID: 24245952 [PubMed - indexed for MEDLINE]
Discriminative Analysis of Brain Functional Connectivity Patterns for Mental Fatigue Classification.
Ann Biomed Eng. 2014 Jun 25;
Authors: Sun Y, Lim J, Meng J, Kwok K, Thakor N, Bezerianos A
Mental fatigue is a commonly experienced state that can be induced by placing heavy demands on cognitive systems. This often leads to lowered productivity and increased safety risks. In this study, we developed a functional-connectivity based mental fatigue monitoring method. Twenty-six subjects underwent a 20-min mentally demanding test of sustained attention with high-resolution EEG monitoring. Functional connectivity patterns were obtained on the cortical surface via source localization of cortical activities in the first and last 5-min quartiles of the experiment. Multivariate pattern analysis was then adopted to extract the highly discriminative functional connectivity information. The algorithm used in the present study demonstrated an overall accuracy of 81.5% (p < 0.0001) for fatigue classification through leave-one-out cross validation. Moreover, we found that the most discriminative connectivity features were located in or across middle frontal gyrus and several motor areas, in agreement with the important role that these cortical regions play in the maintenance of sustained attention. This work therefore demonstrates the feasibility of a functional-connectivity-based mental fatigue assessment method, opening up a new avenue for modeling natural brain dynamics under different mental states. Our method has potential applications in several domains, including traffic and industrial safety.
PMID: 24962984 [PubMed - as supplied by publisher]
The Analytic Bilinear Discrimination of Single-Trial EEG Signals in Rapid Image Triage.
PLoS One. 2014;9(6):e100097
Authors: Yu K, Ai-Nashash H, Thakor N, Li X
The linear discriminant analysis (LDA) method is a classical and commonly utilized technique for dimensionality reduction and classification in brain-computer interface (BCI) systems. Being a first-order discriminator, LDA is usually preceded by the feature extraction of electroencephalogram (EEG) signals, as multi-density EEG data are of second order. In this study, an analytic bilinear classification method which inherits and extends LDA is proposed. This method considers 2-dimentional EEG signals as the feature input and performs classification using the optimized complex-valued bilinear projections. Without being transformed into frequency domain, the complex-valued bilinear projections essentially spatially and temporally modulate the phases and magnitudes of slow event-related potentials (ERPs) elicited by distinct brain states in the sense that they become more separable. The results show that the proposed method has demonstrated its discriminating capability in the development of a rapid image triage (RIT) system, which is a challenging variant of BCIs due to the fast presentation speed and consequently overlapping of ERPs.
PMID: 24933017 [PubMed - as supplied by publisher]
Chronic Treatment with Mood-Stabilizers Attenuates Abnormal Hyperlocomotion of GluA1-Subunit Deficient Mice.
PLoS One. 2014;9(6):e100188
Authors: Maksimovic M, Vekovischeva OY, Aitta-Aho T, Korpi ER
Abnormal excitatory glutamate neurotransmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1-/- mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1-/- mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1-/- mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but ran similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1-/- mouse line can be utilized in screening for new therapeutics.
PMID: 24932798 [PubMed - as supplied by publisher]
Single cell kinase signaling assay using pinched flow coupled droplet microfluidics.
Biomicrofluidics. 2014 May;8(3):034104
Authors: Ramji R, Wang M, Bhagat AA, Tan Shao Weng D, Thakor NV, Teck Lim C, Chen CH
Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5?cm). In this study, we developed a short pinched flow channel (5?mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12?h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib.
PMID: 24926389 [PubMed - as supplied by publisher]
Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.
J Neural Eng. 2014 Jun 12;11(4):046007
Authors: Perge JA, Zhang S, Malik WQ, Homer ML, Cash S, Friehs G, Eskandar EN, Donoghue JP, Hochberg LR
Objective. Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Significance. Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041.).
PMID: 24921388 [PubMed - as supplied by publisher]
A brain-computer interface for single-trial detection of gait initiation from movement related cortical potentials.
Clin Neurophysiol. 2014 May 20;
Authors: Jiang N, Gizzi L, Mrachacz-Kersting N, Dremstrup K, Farina D
OBJECTIVE: Applications of brain-computer interfacing (BCI) in neurorehabilitation have received increasing attention. The intention to perform a motor task can be detected from scalp EEG and used to control rehabilitation devices, resulting in a patient-driven rehabilitation paradigm. In this study, we present and validate a BCI system for detection of gait initiation using movement related cortical potentials (MRCP).
METHODS: The templates of MRCP were extracted from 9-channel scalp EEG during gait initiation in 9 healthy subjects. Independent component analysis (ICA) was used to remove artifacts, and the Laplacian spatial filter was applied to enhance the signal-to-noise ratio of MRCP. Following these pre-processing steps, a matched filter was used to perform single-trial detection of gait initiation.
RESULTS: ICA preprocessing was shown to significantly improve the detection performance. With ICA preprocessing, across all subjects, the true positive rate (TPR) of the detection was 76.9±8.97%, and the false positive rate was 2.93±1.09 per minute.
CONCLUSION: The results demonstrate the feasibility of detecting the intention of gait initiation from EEG signals, on a single trial basis.
SIGNIFICANCE: The results are important for the development of new gait rehabilitation strategies, either for recovery/replacement of function or for neuromodulation.
PMID: 24910150 [PubMed - as supplied by publisher]
Motor modules of human locomotion: influence of EMG averaging, concatenation, and number of step cycles.
Front Hum Neurosci. 2014;8:335
Authors: Oliveira AS, Gizzi L, Farina D, Kersting UG
Locomotion can be investigated by factorization of electromyographic (EMG) signals, e.g., with non-negative matrix factorization (NMF). This approach is a convenient concise representation of muscle activities as distributed in motor modules, activated in specific gait phases. For applying NMF, the EMG signals are analyzed either as single trials, or as averaged EMG, or as concatenated EMG (data structure). The aim of this study is to investigate the influence of the data structure on the extracted motor modules. Twelve healthy men walked at their preferred speed on a treadmill while surface EMG signals were recorded for 60s from 10 lower limb muscles. Motor modules representing relative weightings of synergistic muscle activations were extracted by NMF from 40 step cycles separately (EMGSNG), from averaging 2, 3, 5, 10, 20, and 40 consecutive cycles (EMGAVR), and from the concatenation of the same sets of consecutive cycles (EMGCNC). Five motor modules were sufficient to reconstruct the original EMG datasets (reconstruction quality >90%), regardless of the type of data structure used. However, EMGCNC was associated with a slightly reduced reconstruction quality with respect to EMGAVR. Most motor modules were similar when extracted from different data structures (similarity >0.85). However, the quality of the reconstructed 40-step EMGCNC datasets when using the muscle weightings from EMGAVR was low (reconstruction quality ~40%). On the other hand, the use of weightings from EMGCNC for reconstructing this long period of locomotion provided higher quality, especially using 20 concatenated steps (reconstruction quality ~80%). Although EMGSNG and EMGAVR showed a higher reconstruction quality for short signal intervals, these data structures did not account for step-to-step variability. The results of this study provide practical guidelines on the methodological aspects of synergistic muscle activation extraction from EMG during locomotion.
PMID: 24904375 [PubMed]
Stereovision and augmented reality for closed-loop control of grasping in hand prostheses.
J Neural Eng. 2014 Jun 3;11(4):046001
Authors: Markovic M, Dosen S, Cipriani C, Popovic D, Farina D
Objective. Technologically advanced assistive devices are nowadays available to restore grasping, but effective and effortless control integrating both feed-forward (commands) and feedback (sensory information) is still missing. The goal of this work was to develop a user friendly interface for the semi-automatic and closed-loop control of grasping and to test its feasibility. Approach. We developed a controller based on stereovision to automatically select grasp type and size and augmented reality (AR) to provide artificial proprioceptive feedback. The system was experimentally tested in healthy subjects using a dexterous hand prosthesis to grasp a set of daily objects. The subjects wore AR glasses with an integrated stereo-camera pair, and triggered the system via a simple myoelectric interface. Main results. The results demonstrated that the subjects got easily acquainted with the semi-autonomous control. The stereovision grasp decoder successfully estimated the grasp type and size in realistic, cluttered environments. When allowed (forced) to correct the automatic system decisions, the subjects successfully utilized the AR feedback and achieved close to ideal system performance. Significance. The new method implements a high level, low effort control of complex functions in addition to the low level closed-loop control. The latter is achieved by providing rich visual feedback, which is integrated into the real life environment. The proposed system is an effective interface applicable with small alterations for many advanced prosthetic and orthotic/therapeutic rehabilitation devices.
PMID: 24891493 [PubMed - as supplied by publisher]
Towards User-Friendly Spelling with an Auditory Brain-Computer Interface: The CharStreamer Paradigm.
PLoS One. 2014;9(6):e98322
Authors: Höhne J, Tangermann M
Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI) aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: "CharStreamer". The speller can be used with an instruction as simple as "please attend to what you want to spell". The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions) is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n?=?10) of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences.
PMID: 24886978 [PubMed - as supplied by publisher]
The effective neural drive to muscles is the common synaptic input to motor neurons.
J Physiol. 2014 May 23;
Authors: Farina D, Negro F, Dideriksen JL
We analyzed the transformation of synaptic input to the pool of motor neurons into the neural drive to the muscle. The aim was to explain the relations between common oscillatory signals sent to motor neurons and the effective component of the neural signal sent to muscles as output of the spinal cord circuitries. The approach is based on theoretical derivations, computer simulations, and experiments. It is shown theoretically that for frequencies smaller than the average discharge rates of the motor neurons, the pool of motor neurons determines a pure amplification of the frequency components common to all motor neurons, so that the common input is transmitted almost undistorted and the non-common components are strongly attenuated. The effective neural drive to the muscle thus mirrors the common synaptic input to motor neurons. The simulations with three models of motor neuron confirmed the theoretical results by showing that the coherence function between common input components and the neural drive to the muscle tends to one when increasing the number of active motor neurons. This result, which was relatively insensitive to the type of model used, was also supported experimentally by observing that, in the low-pass signal bandwidth, the peak in coherence between groups of motor units of the abductor digiti minimi muscle of 5 healthy subjects tended to one when increasing the number of motor units. These results have implications for our understanding of the neural control of muscles as well as for methods used for estimating the strength of common input to populations of motor neurons. This article is protected by copyright. All rights reserved.
PMID: 24860172 [PubMed - as supplied by publisher]
The Right Dorsal Habenula Limits Attraction to an Odor in Zebrafish.
Curr Biol. 2014 May 21;
Authors: Krishnan S, Mathuru AS, Kibat C, Rahman M, Lupton CE, Stewart J, Claridge-Chang A, Yen SC, Jesuthasan S
BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays.
RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance.
CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.
PMID: 24856207 [PubMed - as supplied by publisher]