Instrumentation for electrodiagnostic studies.

The instrument and accessories are an important part of the electrodiagnostic (EDX) testing. Their functional understanding is useful to recognize and reduce various artifacts and noise/interference in the signal. In this review, we will describe the technical specifications of various components of the instrument, and their effect on signals and noise. This will be illustrated using example of electromyography and nerve conduction studies. However the same principles also apply to other modalities of testing. We will also provide general strategies to reduce noise and artifacts, followed by some modality specific examples.

Interactions between egocentric and allocentric spatial coding of sounds revealed by a multisensory learning paradigm.

Although sound position is initially head-centred (egocentric coordinates), our brain can also represent sounds relative to one another (allocentric coordinates). Whether reference frames for spatial hearing are independent or interact remained largely unexplored. Here we developed a new allocentric spatial-hearing training and tested whether it can improve egocentric sound-localisation performance in normal-hearing adults listening with one ear plugged. Two groups of participants (N = 15 each) performed an egocentric sound-localisation task (point to a syllable), in monaural listening, before and after 4-days of multisensory training on triplets of white-noise bursts paired with occasional visual feedback. Critically, one group performed an allocentric task (auditory bisection task), whereas the other processed the same stimuli to perform an egocentric task (pointing to a designated sound of the triplet). Unlike most previous works, we tested also a no training group (N = 15). Egocentric sound-localisation abilities in the horizontal plane improved for all groups in the space ipsilateral to the ear-plug. This unexpected finding highlights the importance of including a no training group when studying sound localisation re-learning. Yet, performance changes were qualitatively different in trained compared to untrained participants, providing initial evidence that allocentric and multisensory procedures may prove useful when aiming to promote sound localisation re-learning.

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain.

The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. OBJECTIVE: We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3-5 mm depths without inserting fibers into the cortex. APPROACH: Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. MAIN RESULTS: The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200-500 mm3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. SIGNIFICANCE: The present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.

Assessment of vestibulo-ocular function without measuring eye movements.

BACKGROUND: The vestibulo-ocular reflex (VOR) maintains stable gaze during head motion. Deficiencies lead to apparent world motion due to incomplete stabilization of eyes in space. VOR measurement requires specialized apparatus, trained operators, and significant setup time. NEW METHOD: We present a system (VON: vestibulo-ocular nulling) for rapid vestibulo-ocular assessment without measuring eye movements per se. VON uses a head-mounted motion sensor, laptop computer with user input control, and laser target whose position is controlled by the computer. As the head moves, the target is made to move in the same manner with a gain set by the subject. When the subject sets the gain so the target appears stationary in space, it is stationary on the retinas. One can determine from this gain the extent to which the eyes move in space when the head moves, which is the amount by which the VOR is deficient. From this the gain of the compensatory eye movements is derived. RESULTS: VON was compared with conventional video-based VOR measures. Both methods track expected changes in gain over 20min of adaptation to minifying spectacles. VON measures are more consistent across subjects, and pre-adaptation values are closer to compensatory. COMPARISON WITH EXISTING METHOD: VON is a rapid means to assess vestibulo-ocular performance. As a functional perceptual measure, it accounts for gaze-stabilizing contributions that are not apparent in the standard VOR, such as pursuit and perceptual tolerance. CONCLUSIONS: VON assesses functional VOR performance. Future implementations will make VOR assessment widely available to investigators and clinicians.

Alpha-range visual and auditory stimulation reduces the perception of pain.

BACKGROUND: Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz. METHODS: Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency. We collected verbal pain ratings of laser stimuli from participants following 10 minutes of flashing LED goggle stimulation and 10 minutes of binaural beat stimulation across the alpha range. Alterations in sleepiness, anxiety and negative mood were recorded following each auditory or visual alpha-rhythm stimulation session. RESULTS: A significant reduction in pain ratings was found after both the visual and the auditory stimulation across all three frequencies compared with the control condition. In the visual group, a significantly larger reduction was recorded following the 10-Hz stimulation than succeeding the 8- and 12-Hz conditions. CONCLUSIONS: This study suggests that a short presentation of auditory and visual stimuli, oscillating in the alpha range, have an analgesic effect on acute laser pain, with the largest effect following the 10-Hz visual stimulation. Pain reductions following stimulation in the alpha range are independent of sleepiness, anxiety, and negative moods. SIGNIFICANCE: This study provides new behavioural evidence showing that visual and auditory entrainment of frequencies in the alpha-wave range can influence the perception of acute pain in humans.

Head mounted DMD based projection system for natural and prosthetic visual stimulation in freely moving rats.

Novel technologies are constantly under development for vision restoration in blind patients. Many of these emerging technologies are based on the projection of high intensity light patterns at specific wavelengths, raising the need for the development of specialized projection systems. Here we present and characterize a novel projection system that meets the requirements for artificial retinal stimulation in rats and enables the recording of cortical responses. The system is based on a customized miniature Digital Mirror Device (DMD) for pattern projection, in both visible (525 nm) and NIR (915 nm) wavelengths, and a lens periscope for relaying the pattern directly onto the animal's retina. Thorough system characterization and the investigation of the effect of various parameters on obtained image quality were performed using ZEMAX. Simulation results revealed that images with an MTF higher than 0.8 were obtained with little effect of the vertex distance. Increased image quality was obtained at an optimal pupil diameter and smaller field of view. Visual cortex activity data was recorded simultaneously with pattern projection, further highlighting the importance of the system for prosthetic vision studies. This novel head mounted projection system may prove to be a vital tool in studying natural and artificial vision in behaving animals.

Monte Carlo analysis of the enhanced transcranial penetration using distributed near-infrared emitter array.

Transcranial near-infrared (NIR) treatment of neurological diseases has gained recent momentum. However, the low NIR dose available to the brain, which shows severe scattering and absorption of the photons by human tissues, largely limits its effectiveness in clinical use. Hereby, we propose to take advantage of the strong scattering effect of the cranial tissues by applying an evenly distributed multiunit emitter array on the scalp to enhance the cerebral photon density while maintaining each single emitter operating under the safe thermal limit. By employing the Monte Carlo method, we simulated the transcranial propagation of the array emitted light and demonstrated markedly enhanced intracranial photon flux as well as improved uniformity of the photon distribution. These enhancements are correlated with the source location, density, and wavelength of light. To the best of our knowledge, we present the first systematic analysis of the intracranial light field established by the scalp-applied multisource array and reveal a strategy for the optimization of the therapeutic effects of the NIR radiation.

Emulated laser-acupuncture system.

A novel laser-acupuncture system was developed that can be used to implement the manipulation methods of traditional acupuncture, such as lifting and thrusting. A 780 nm laser diode with a maximum power of 90 mW was used as the light source. The focus point of the laser beam was adjustable by changing the position of the lens, facilitating the implementation of the lifting and thrusting methods of traditional Chinese medicine and achieving various stimulation depths at the acupuncture point. The images for the light spots from the outlet of the emulated laser acupuncture were captured at various distances and their sizes were calculated. The result showed that the diameter of the focused light spot (i.e., at the focus point) was 0.11 mm, which is close to the diameter of commonly used needles (with diameters of approximately 0.22 mm). The area of the light spot 1 cm from the focus point was approximately 50 times larger, indicating that the unit power might be 1/50 of the power of the focus point. To study the effect of emulated laser acupuncture on human meridians, after stimulating the Shenmen point (HT7) of five subjects and obtaining their Ryodoraku values of the heart meridian and the small-intestine meridian, a paired t test showed that the laser stimulation incorporating lifting and thrusting was significantly higher than the laser stimulation without lifting and thrusting (p<0.05). The result is consistent with traditional acupuncture in that acupuncture incorporating lift and thrust is more effective than that without lift and thrust.

An independent SSVEP-based brain-computer interface in locked-in syndrome.

OBJECTIVE: Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use with severely disabled patients. Gaze-independent SSVEP-BCIs have been designed but have shown a drop in accuracy and have not been tested in brain-injured patients. In the present paper, we propose a novel independent SSVEP-BCI based on covert attention with an improved classification rate. We study the influence of feature extraction algorithms and the number of harmonics. Finally, we test online communication on healthy volunteers and patients with locked-in syndrome (LIS). APPROACH: Twenty-four healthy subjects and six LIS patients participated in this study. An independent covert two-class SSVEP paradigm was used with a newly developed portable light emitting diode-based 'interlaced squares' stimulation pattern. MAIN RESULTS: Mean offline and online accuracies on healthy subjects were respectively 85 ± 2% and 74 ± 13%, with eight out of twelve subjects succeeding to communicate efficiently with 80 ± 9% accuracy. Two out of six LIS patients reached an offline accuracy above the chance level, illustrating a response to a command. One out of four LIS patients could communicate online. SIGNIFICANCE: We have demonstrated the feasibility of online communication with a covert SSVEP paradigm that is truly independent of all neuromuscular functions. The potential clinical use of the presented BCI system as a diagnostic (i.e., detecting command-following) and communication tool for severely brain-injured patients will need to be further explored.

Photo-acoustic excitation and optical detection of fundamental flexural guided wave in coated bone phantoms.

Photo-acoustic (PA) imaging was combined with skeletal quantitative ultrasound (QUS) for assessment of human long bones. This approach permitted low-frequency excitation and detection of ultrasound so as to efficiently receive the thickness-sensitive fundamental flexural guided wave (FFGW) through a coating of soft tissue. The method was tested on seven axisymmetric bone phantoms, whose 1- to 5-mm wall thickness and 16-mm diameter mimicked those of the human radius. Phantoms were made of a composite material and coated with a 2.5- to 7.5-mm layer of soft material that mimicked soft tissue. Ultrasound was excited with a pulsed Nd:YAG laser at 1064-nm wavelength and received on the same side of the coated phantom with a heterodyne interferometer. The FFGW was detected at 30-kHz frequency. Fitting the FFGW phase velocity by the FLC(1,1) tube mode provided an accurate (9.5 ± 4.0%) wall thickness estimate. Ultrasonic in vivo characterization of cortical bone thickness may thus become possible.

Commanding a robotic wheelchair with a high-frequency steady-state visual evoked potential based brain-computer interface.

This work presents a brain-computer interface (BCI) used to operate a robotic wheelchair. The experiments were performed on 15 subjects (13 of them healthy). The BCI is based on steady-state visual-evoked potentials (SSVEP) and the stimuli flickering are performed at high frequency (37, 38, 39 and 40 Hz). This high frequency stimulation scheme can reduce or even eliminate visual fatigue, allowing the user to achieve a stable performance for long term BCI operation. The BCI system uses power-spectral density analysis associated to three bipolar electroencephalographic channels. As the results show, 2 subjects were reported as SSVEP-BCI illiterates (not able to use the BCI), and, consequently, 13 subjects (12 of them healthy) could navigate the wheelchair in a room with obstacles arranged in four distinct configurations. Volunteers expressed neither discomfort nor fatigue due to flickering stimulation. A transmission rate of up to 72.5 bits/min was obtained, with an average of 44.6 bits/min in four trials. These results show that people could effectively navigate a robotic wheelchair using a SSVEP-based BCI with high frequency flickering stimulation.

Warning navigation system using real-time safe region monitoring for otologic surgery.

PURPOSE: We developed a surgical navigation system that warns the surgeon with auditory and visual feedback to protect the facial nerve with real-time monitoring of the safe region during drilling. METHODS: Warning navigation modules were developed and integrated into a free open source software platform. To obtain high registration accuracy, we used a high-precision laser-sintered template of the patient's bone surface to register the computed tomography (CT) images. We calculated the closest distance between the drill tip and the surface of the facial nerve during drilling. When the drill tip entered the safe regions, the navigation system provided an auditory and visual signal which differed in each safe region. To evaluate the effectiveness of the system, we performed phantom experiments for maintaining a given safe margin from the facial nerve when drilling bone models, with and without the navigation system. The error of the safe margin was measured on postoperative CT images. In real surgery, we evaluated the feasibility of the system in comparison with conventional facial nerve monitoring. RESULTS: The navigation accuracy was submillimeter for the target registration error. In the phantom study, the task with navigation ([Formula: see text] mm) was more successful with smaller error, than the task without navigation ([Formula: see text] mm, [Formula: see text]). The clinical feasibility of the system was confirmed in three real surgeries. CONCLUSIONS: This system could assist surgeons in preserving the facial nerve and potentially contribute to enhanced patient safety in the surgery.

A role for silent synapses in the development of the pathway from layer 2/3 to 5 pyramidal cells in the neocortex.

The integration of neurons within the developing cerebral cortex is a prolonged process dependent on a combination of molecular and physiological cues. To examine the latter we used laser scanning photostimulation (LSPS) of caged glutamate in conjunction with whole-cell patch-clamp electrophysiology to probe the integration of pyramidal cells in the sensorimotor regions of the mouse neocortex. In the days immediately after postnatal day 5 (P5) the origin of the LSPS-evoked AMPA receptor (AMPAR)-mediated synaptic inputs were diffuse and poorly defined with considerable variability between cells. Over the subsequent week this coalesced and shifted, primarily influenced by an increased contribution from layers 2/3 cells, which became a prominent motif of the afferent input onto layer 5 pyramidal cells regardless of cortical region. To further investigate this particular emergent translaminar connection, we alternated our mapping protocol between two holding potentials (-70 and +40 mV) allowing us to detect exclusively NMDA receptor (NMDAR)-mediated inputs. This revealed distal MK-801-sensitive synaptic inputs that predict the formation of the mature, canonical layer 2/3 to 5 pathway. However, these were a transient feature and had been almost entirely converted to AMPAR synapses at a later age (P16). To examine the role of activity in the recruitment of early NMDAR synapses, we evoked brief periods (20 min) of rhythmic bursting. Short intense periods of activity could cause a prolonged augmentation of the total input onto pyramidal cells up until P12; a time point when the canonical circuit has been instated and synaptic integration shifts to a more consolidatory phase.

The AB-York crescent of sound: an apparatus for assessing spatial-listening skills in children and adults.

Modern health services need efficient tools for measuring outcomes from interventions, that is, tools of proven efficacy which make minimal demands on the time of clinicians in learning to administer tests and in interpreting results. This paper describes an apparatus designed to meet those requirements. The apparatus administers performance tests of spatial listening for children and adults with unilateral and bilateral cochlear implants. The apparatus was designed with guidance from clinicians. It possesses three key attributes: it is simple to use; the results of tests are scored automatically and are compared with reference data; the apparatus generates comprehensive personalized reports for individual participants that can be included in clinical notes. This paper describes the apparatus and reports results of a test measuring spatial release from masking of speech which illustrates the compatibility between the new apparatus and an older apparatus with which the reference data were gathered.

A new technique for controlling the brain: optogenetics and its potential for use in research and the clinic.

The recent development of optogenetic techniques has generated considerable excitement in neuroscience research. Optogenetics uses light to control the activity of neurons which have been modified to express light-sensitive proteins. Some proteins, such as channelrhodopsin, are cation channels that produce depolarization of neurons when illuminated. In other cases, neuronal activity can be inhibited through illumination of proteins, such as the chloride pump halorhodopsin, that hyperpolarize neurons. Because these proteins can be selectively expressed in specific cell types and/or in specific locations, optogenetics avoids several of the non-specific effects of electrical or pharmacological brain stimulation. This short review will explain the physiology of this technique, describe the basic and technical aspects of the method, and highlight some of the research as well as the clinical potential of optogenetics.

Acousto-optic laser scanning for multi-site photo-stimulation of single neurons in vitro.

To study the complex synaptic interactions underpinning dendritic information processing in single neurons, experimenters require methods to mimic presynaptic neurotransmitter release at multiple sites with no physiological damage. We show that laser scanning systems built around large-aperture acousto-optic deflectors and high numerical aperture objective lenses provide the sub-millisecond, sub-micron precision necessary to achieve physiological, exogenous synaptic stimulation. Our laser scanning systems can produce the sophisticated spatio-temporal patterns of synaptic input that are necessary to investigate single-neuron dendritic physiology.

Suppression of melatonin secretion in healthy subjects with eyeglass LED delivery system.

OBJECTIVE: Practicability remains a problem in light therapy of biological rhythm disorders. We report here the effect on melatonin secretion of a device consisting of a prototype of eyeglasses including light emitting diodes (LED) in lenses (Somnavue). METHODS: Light (1,200 lx) was administered in a randomised crossover design to ten healthy subjects with Somnavue for 1 or 2 hours, Lumino (a helmet which administers light) for 1 hour, and placebo, beginning at 01:00 h. Plasma melatonin concentrations were evaluated between 20:00-05:00 h. RESULTS: Multiple comparisons showed differences between placebo and Somnavue administered for one or two hours (p<0.01 and p<0.05 respectively) and Lumino and placebo (p<0.05). CONCLUSIONS: In conclusion, Somnavue was able to suppress melatonin. The development of such a device could increase adherence with light treatment in SAD or circadian rhythm sleep disorders.

Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator.

We implemented a light-sensing function on CMOS-based multi-chip stimulator for retinal prosthesis. Using the light-sensing circuitry attached to each stimulation electrode, the flexible multi-chip stimulator is capable of image-based patterned stimulation. We verified the function of the light-controlled decision based on the light intensity measured just beside the stimulation site. We also experimentally demonstrated in vivo retinal stimulation on rabbit's retina with light-controlled decision. The result of the present work is a simplified demonstration for the concept of retinal prosthesis with on-site imaging.

[A discussion about key issues in retinal prosthesis].

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are two predominant causes of visual deterioration. Retinal prosthesis embeds a micro-electric chip or a micro-photoelectric diode array in the sub-retina or epi-retina, which is used to stimulate the remainder of inner retina, so as to restore some degree of sight. Retinal prosthesis has attracted most attention in the field of artificial visual function recovery, and along with deep-going research, many issues need to be resolved. In this paper, the theory of retinal prosthesis and the status quo of research in many countries are introduced, the key issues which influence the application of the retinal prosthesis are discussed in detail, and some notions and advices are presented.