A fast perfusion system for single cell physiology optimized for microscopes with water immersion objectives

A perfusion system was constructed which allows the fast application of different solutes underneath a water immersion objective. The perfusion system is mounted into the immersion objective by milling a slot into the frontal metal plate of the lens holder. It consists of a five-channel pipette fixed to the objective and solution reservoirs gated by computer controlled magnetic valves. Up to five different solutions can be applied to the specimen under study. The solution between objective and specimen is completely exchanged after 1–2 s as determined from fluorescence measurements. This arrangement is optimized for [Ca²⁺] measurements with a fluorescence measurement system in tissue slices, where upright microscopes are required. It offers the advantage of saving a micromanipulator for the perfusion pipette and facilitates a fast, reproducible and precise positioning of the perfusion system.     

The multi-channel cochlear implant and the relief of severe-to-profound deafness

Abstract

This personal reflection outlines the discoveries at the University of Melbourne leading to the multi-channel cochlear implant, and its development industrially by Cochlear Limited. My earlier experimental electrophysiological research demonstrated temporal coding occurred for only low frequencies, i.e. below 200–500 pulses/second. I was able to confirm these findings perceptually in behaviourally conditioned animals. In addition, these studies showed that temporal discrimination occurred across spatial coding channels. These experimental results correlated with the later conscious experience for electrical stimulation in my implant patients. In addition, the mid-to-high frequencies were coded in part by place of stimulation using bipolar and monopolar stimulation to restrict current spread. Furthermore, place of stimulation had the qualities of sharpness and dullness, and was also experienced as vowels. Owing to the limitation in coding speech with a physiological model due to the overlap of electrical current leading to unpredictable variations in loudness, a speech coding strategy that extracted the most important speech features for transmission through an electro-neural ‘bottle-neck’ to the brain was explored. Our inaugural strategy, discovered in 1978, extracted the second formant for place of stimulation, voicing for rate of stimulation, and sound pressure for current level. This was the first coding strategy to provide open-set speech understanding, as shown by standard audiological tests, and it became the first clinically successful interface between the world and human consciousness. This strategy was improved with place coding for the third formant or high-frequency spectrum, and then the spectral maxima. In 1989, I operated on our first patient to receive a bilateral implant, and in 1990, the first with a bimodal processor. The psychophysics and speech perception for these showed that the stimuli from each side could be fused into a single image, and localized according to differences in intensity and time of arrival of the stimuli. There were significant improvements for speech perception in noise. In 1985, I implanted our first children with the multi-channel prosthesis and found that speech understanding and spoken language were greatly improved the younger the child at surgery, and especially when younger than 12 months. Speech understanding was strongly related to the development of place coding. In 1990, the US Food and Drug Administration approved the implant for deaf children, the first by any world health regulatory body making it the first major advance in helping deaf children to communicate.     

Development of visual texture segregation during the first year of life: a high-density electrophysiological study

There are important developmental changes occurring during infancy in visual cortical structures that underlie higher-order perceptual abilities. Using high-density electrophysiological recording techniques, the present study aimed to examine the development of visual mechanisms, during the first year of life, associated with texture segregation. Forty-two normal full term infants were tested at 1, 3, 6 or 12 months of age. Visual-evoked potentials to low-level stimuli varying in orientation (oriVEP) and higher-level textured stimuli (texVEP) were recorded from 128 scalp electrodes. Difference potentials were obtained to extract the VEP component associated specifically with texture segregation (tsVEP). Results show a clear developmental pattern regarding amplitude, latency and scalp distribution of tsVEP, which appears at around 3 months but does not reach maturity by 12 months of age. A reduction in latency is particularly evident between 3 and 6 months, whereas amplitude shows a gradual increase with a marked increment between 3 and 6 months for low-level orientation stimuli and between 6 and 12 months for higher-level textured stimuli. These developmental patterns are attributed to neural maturational processes such as myelination and synaptogenesis. The differential developmental rates can be explained by delayed maturational processes of brain regions involved in more complex visual processing.     

猕猴脑部多通道接收线圈的仿真与设计

目的介绍一种用于消除磁共振线圈通道间耦合的仿真方法,指导猕猴脑部线圈的设计。材料与方法通过电磁场及电路仿真软件,计算线圈周围的空间电磁场分布及S参数,以观测通道间的耦合影响。结果在猕猴脑部接收线圈的设计过程中,通过仿真通道间的耦合可知:当相邻一组线圈的几何中心相距42.2 mm时,其耦合影响可以忽略不计,达到了线圈的设计要求。结论利用本文介绍的仿真方法,实现了猕猴脑部多通道线圈的去耦设计。在线圈的制作过程中,该方法可以明确优化方向,降低线圈的研发成本。     

STN DBS of Advanced Parkinson's Disease Experienced in a Specialized Monitoring Unit with a Prospective Protocol

Objective

In the evaluation of patients with Parkinson''s disease (PD), most neurologists only see their patients during a limited period of their fluctuating 24-hour-a-day lives. This study aimed to assess the short-term outcome of STN stimulation for patients with advanced PD evaluated in a 24-hour monitoring unit for movement disorder (MUMD) using a prospective protocol.

Methods

Forty-two patients with advanced PD consecutively treated with bilateral STN stimulation using multi-channel microelectrode recording were included in this study. All patients were evaluated using a 24-hour MUMD with a video recording/editing system and were evaluated with a prospective protocol of the Unified Parkinson''s Disease Rating Scale, Hoehn and Yahr Staging, Schwab and England Activities of Daily Living, levodopa equivalent daily dose (LEDD), Short Form-36 Health Survey, and neuropsychological tests. Magnetic resonance (MR) images of the brain were performed prior to and six months after surgery.

Results

All patients were evaluated at three and six months after surgery. There was a rapid and significant improvement of the motor symptoms, especially in tremor and rigidity, after STN stimulation with low morbidity. Dyskinesia was markedly decreased with much lowered LEDD values by 50% after STN stimulation. 1.5T MR images were safely taken according to the manufacturer''s guidelines at six months after surgery without any adverse effects in 41 patients treated with STN stimulations.

Conclusion

Evaluations in a 24-hour monitoring unit could reduce the dose of medication efficiently to an optimal level with patients''comfort and improve the clinical symptoms in harmony with STN stimulation.     

Wireless multi-channel single unit recording in freely moving and vocalizing primates

The ability to record well-isolated action potentials from individual neurons in naturally behaving animals is crucial for understanding neural mechanisms underlying natural behaviors. Traditional neurophysiology techniques, however, require the animal to be restrained which often restricts natural behavior. An example is the common marmoset (Callithrix jacchus), a highly vocal New World primate species, used in our laboratory to study the neural correlates of vocal production and sensory feedback. When restrained by traditional neurophysiological techniques marmoset vocal behavior is severely inhibited. Tethered recording systems, while proven effective in rodents pose limitations in arboreal animals such as the marmoset that typically roam in a three-dimensional environment. To overcome these obstacles, we have developed a wireless neural recording technique that is capable of collecting single-unit data from chronically implanted multi-electrodes in freely moving marmosets. A lightweight, low power and low noise wireless transmitter (headstage) is attached to a multi-electrode array placed in the premotor cortex of the marmoset. The wireless headstage is capable of transmitting 15 channels of neural data with signal-to-noise ratio (SNR) comparable to a tethered system. To minimize radio-frequency (RF) and electro-magnetic interference (EMI), the experiments were conducted within a custom designed RF/EMI and acoustically shielded chamber. The individual electrodes of the multi-electrode array were periodically advanced to densely sample the cortical layers. We recorded single-unit data over a period of several months from the frontal cortex of two marmosets. These recordings demonstrate the feasibility of using our wireless recording method to study single neuron activity in freely roaming primates.     

EEG Global Field Power Spectrum Changes After a Single Dose of Atypical Antipsychotics in Healthy Volunteers

Effects of four novel atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone) on scalp-recorded multi-channel EEGs were compared with two conventional antipsychotic drugs (chlorpromazine and haloperidol) and placebo in 14 healthy male volunteers. All subjects went through seven sessions. In each session, EEGs were recorded before and 2, 4 and 6 hours after drug administration. Global Field Power (GFP) in delta frequency band (1.5-6 Hz) increased around the time of peak serum concentration of quetiapine and risperidone compared to baseline. The increase of GFP in delta activity after quetiapine was significantly prominent in comparison to two other atypical antipsychotic drugs, perospirone and olanzapine, as well as to typical antipsychotic drugs, chlorpromazine and haloperidol (p<0.05). The increase in GFP of delta after risperidone was more prominent in comparison to after haloperidol (p<0.05). The greater sedative effects after quetiapine and risperidone may reflect the high affinity to A1 and H1 receptor bindings of these drugs. According to Low Resolution Electromagnetic Tomography (LORETA), olanzapine increased the delta in the posterior region indicating a frontal shift of brain activity, suggesting that olanzapine may be useful against negative symptoms in schizophrenics.     

Multi-locus transcranial magnetic stimulation—theory and implementation

Background

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation.

Can individually targeted and optimized multi-channel tDCS outperform standard bipolar tDCS in stimulating the primary somatosensory cortex?

BackgroundTranscranial direct current stimulation (tDCS) has emerged as a non-invasive neuro-modulation technique. Most studies show that anodal tDCS increases cortical excitability, however, with variable outcomes. Previously, we have shown in computer simulations that our multi-channel tDCS (mc-tDCS) approach, the distributed constrained maximum intensity (D-CMI) method can potentially lead to better controlled tDCS results due to the improved directionality of the injected current at the target side for individually optimized D-CMI montages.ObjectiveIn this study, we test the application of the D-CMI approach in an experimental study to stimulate the somatosensory P20/N20 target source in Brodmann area 3b and compare it with standard bipolar tDCS and sham conditions.MethodsWe applied anodal D-CMI, the standard bipolar and D-CMI based Sham tDCS for 10 min to target the 20 ms post-stimulus somatosensory P20/N20 target brain source in Brodmann area 3b reconstructed using combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis in realistic head models with calibrated skull conductivity in a group-study with 13 subjects. Finger-stimulated somatosensory evoked fields (SEF) were recorded and the component at 20 ms post-stimulus (M20) was analyzed before and after the application of the three tDCS conditions in order to read out the stimulation effect on Brodmann area 3b.ResultsAnalysis of the finger stimulated SEF M20 peak before (baseline) and after tDCS shows a significant increase in source amplitude in Brodmann area 3b for D-CMI (6–16 min after tDCS), while no significant effects are found for standard bipolar (6–16 min after tDCS) and sham (6–16 min after tDCS) stimulation conditions. For the later time courses (16–26 and 27–37 min post-stimulation), we found a significant decrease in M20 peak source amplitude for standard bipolar and sham tDCS, while there was no effect for D-CMI.ConclusionOur results indicate that targeted and optimized, and thereby highly individualized, mc-tDCS can outperform standard bipolar stimulation and lead to better control over stimulation outcomes with, however, a considerable amount of additional work compared to standard bipolar tDCS.     

Spike sorting by a minimax reduced feature set based on finite differences

Spikes are classified according to their finite differences in various orders. The fundamental idea that makes it work is that finite differences can extract and isolate features from spikes. This method showed better sorting quality and involved less labor than the methods of principal component analysis, original reduced feature set, and wavelet-based spike classifiers.