Statistical Methods for Neuroscience Research Papers (original) (raw)

2004, Journal of neuroscience methods

We have developed a toolbox and graphic user interface, EEGLAB, running under the cross-platform MATLAB environment (The Mathworks, Inc.) for processing collections of single-trial and/or averaged EEG data of any number of channels. Available functions include EEG data, channel and event information importing, data visualization (scrolling, scalp map and dipole model plotting, plus multi-trial ERP-image plots), preprocessing (including artifact rejection, filtering, epoch selection, and averaging), Independent Component Analysis (ICA) and time/frequency decompositions including channel and component cross-coherence supported by bootstrap statistical methods based on data resampling. EEGLAB functions are organized into three layers. Top-layer functions allow users to interact with the data through the graphic interface without needing to use MATLAB syntax. Menu options allow users to tune the behavior of EEGLAB to available memory. Middle-layer functions allow users to customize data processing using command history and interactive 'pop' functions. Experienced MATLAB users can use EEGLAB data structures and stand-alone signal processing functions to write custom and/or batch analysis scripts. Extensive function help and tutorial information are included. A 'plug-in' facility allows easy incorporation of new EEG modules into the main menu. EEGLAB is freely available (http://www.sccn.ucsd.edu/eeglab/) under the GNU public license for noncommercial use and open source development, together with sample data, user tutorial and extensive documentation.

1985, Journal of Neuroscience Methods

A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated 4--maze consisting of two open arms and two enclosed arms. The use of this test for detecting such drug effects was validated behaviourally, physiologically, and pharmacologically. Rats made significantly fewer entries into the open arms than into the closed arms, and spent significantly less time in open arms. Confinement to the open arms was associated with the observation of significantly more anxiety-related behaviours, and of significantly greater plasma corticosterone concentrations, than confinement to the closed arms. Neither novelty nor illumination was a significant contributor to the behaviour of the rats on the +-maze. A significant increase in the percentage of time spent on the open arms and the number of entries into the open arms was observed only within clinically effective anxiolytics (chlordiazepoxide, diazepam and, less effectively, phenobarbitone). Compounds that cause anxiety in man significantly reduced the percentage of entries into, and time spent on, the open arms (yohimbine, pentylenetetrazole, caffeine, amphetamine). Neither antidepressants nor major tranquilisers had a specific effect. Exposure to a holeboard immediately before placement on the +-maze showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.

2007

In this paper, we show how ElectroEncephaloGraphic (EEG) and MagnetoEncephaloGraphic (MEG) data can be analyzed statistically using nonparametric techniques. Nonparametric statistical tests offer complete freedom to the user with respect to the test statistic by means of which the experimental conditions are compared. This freedom provides a straightforward way to solve the multiple comparisons problem (MCP) and it allows to incorporate biophysically motivated constraints in the test statistic, which may drastically increase the sensitivity of the statistical test. The paper is written for two audiences: (1) empirical neuroscientists looking for the most appropriate data analysis method, and (2) methodologists interested in the theoretical concepts behind nonparametric statistical tests. For the empirical neuroscientist, a large part of the paper is written in a tutorial-like fashion, enabling neuroscientists to construct their own statistical test, maximizing the sensitivity to the expected effect. And for the methodologist, it is explained why the nonparametric test is formally correct. This means that we formulate a null hypothesis (identical probability distribution in the different experimental conditions) and show that the nonparametric test controls the false alarm rate under this null hypothesis.

2005, Journal of Neuroscience Methods

The physical basis for electrical stimulation of excitable tissue, as used by electrophysiological researchers and clinicians in functional electrical stimulation, is presented with emphasis on the fundamental mechanisms of charge injection at the electrode/tissue interface. Faradaic and non-Faradaic charge transfer mechanisms are presented and contrasted. An electrical model of the electrode/tissue interface is given. The physical basis for the origin of electrode potentials is given. Various methods of controlling charge delivery during pulsing are presented. Electrochemical reversibility is discussed. Commonly used electrode materials and stimulation protocols are reviewed in terms of stimulation efficacy and safety. Principles of stimulation of excitable tissue are reviewed with emphasis on efficacy and safety. Mechanisms of damage to tissue and the electrode are reviewed.

2011, Journal of Neuroscience Methods

The natural history of recovery of motor function after stroke is described using data from a 1-year community-based study in Auckland, New Zealand. Of 680 patients, 88% presented with a hemiparesis; the proportion of survivors with a persisting deficit declined to 71% at 1 month and 62% at 6 months after the onset of the stroke. At onset, there were equal proportions of people with mild, moderate, and severe motor deficits, but the majority (76%) of those who survived 6 months had either no or only a mild deficit. Recovery of motor function was associated with the stroke severity but not with age or sex; patients with a mild motor deficit at onset were 10 times more likely to recover their motor function than those with a severe stroke. Our results confirm the reasonably optimistic outcome for survivors of stroke and further suggest that recovery of motor function is confined to patients whose motor deficit at onset is either mild or moderate.

1989, Journal of Neuroscience Methods

We describe methods for obtaining stable, whole-cell recordings from neurons in brain hermspheres from turtles and m brain shces from rats and turtles Synaptlc currents and membrane properties of central neurons can be stud~ed m voltage and current clamp m cells maintained wlttun their endogenous synapnc circuits. The methods described here are compatible wtth unmodified dissecting microscopes and recording chambers, and with brain shces of standard thickness (400-500 ~tm).

2010, Journal of Neuroscience Methods

Electrodermal activity is characterized by the superposition of what appear to be single distinct skin conductance responses (SCRs). Classic trough-to-peak analysis of these responses is impeded by their apparent superposition. A deconvolution approach is proposed, which separates SC data into continuous signals of tonic and phasic activity. The resulting phasic activity shows a zero baseline, and overlapping SCRs are represented by predominantly distinct, compact impulses showing an average duration of less than 2 s. A time integration of the continuous measure of phasic activity is proposed as a straightforward indicator of event-related sympathetic activity. The quality and benefit of the proposed measure is demonstrated in an experiment with short interstimulus intervals as well as by means of a simulation study. The advances compared to previous decomposition methods are discussed.

2008, Journal of neuroscience …

Understanding the pathophysiogenesis of temporal lobe epilepsy (TLE) largely rests on the use of models of status epilepticus (SE), as in the case of the pilocarpine model. The main features of TLE are: (i) epileptic foci in the limbic system; (ii) an "initial precipitating injury"; (iii) the so-called "latent period"; and (iv) the presence of hippocampal sclerosis leading to reorganization of neuronal networks. Many of these characteristics can be reproduced in rodents by systemic injection of pilocarpine; in this animal model, SE is followed by a latent period and later by the appearance of spontaneous recurrent seizures (SRSs). These processes are, however, influenced by experimental conditions such as rodent species, strain, gender, age, doses and routes of pilocarpine administration, as well as combinations with other drugs administered before and/or after SE. In the attempt to limit these sources of variability, we evaluated the methodological procedures used by several investigators in the pilocarpine model; in particular, we have focused on the behavioural, electrophysiological and histopathological findings obtained with different protocols. We addressed the various experimental approaches published to date, by comparing mortality rates, onset of SRSs, neuronal damage, and network reorganization. Based on the evidence reviewed here, we propose that the pilocarpine model can be a valuable tool to investigate the mechanisms involved in TLE, and even more so when standardized to reduce mortality at the time of pilocarpine injection, differences in latent period duration, variability in the lesion extent, and SRS frequency.

2002, Journal of Neuroscience Methods

Adult animals continue to produce new neurons in the dentate gyrus of hippocampus. Until now, the principal method of studying neurogenesis has been to inject either tritiated thymidine or 5?-Bromo-2-deoxyuridine (BrdU) intraperitoneally followed by autoradiographic or immunohistochemical detection methods respectively. However, such exogenous markers may produce toxic effects. Our objective was to determine whether Ki-67, a nuclear protein expressed in all phases of the cell cycle except the resting phase, can be used as an alternative, endogenous marker. Using immunohistochemistry, we examined Ki-67 and BrdU expression pattern in rats. Ki-67 was expressed within the proliferative zone of the dentate gyrus and its expression pattern mimicked that of BrdU when examined soon after exogenous BrdU administration. Quantitative comparison of BrdU and Ki-67-positive cells showed 50% higher numbers of the latter when examined 24 h after the BrdU injection. This was expected, since BrdU can be incorporated into DNA only during the S-phase of the mitotic process, whereas Ki-67 is expressed for its whole duration. Experimental increases (by ischemia) or reductions (by radiation) in the number of mitotic cells produced parallel changes in BrdU and Ki-67 signals. Thus, Ki-67 is an effective mitotic marker and has most of the benefits of BrdU and none of the costs. This study provides evidence for Ki-67 to be used as a marker of proliferation in the initial phase of adult neurogenesis. #

2008, Journal of Neuroscience Methods

This study examines the effects of expanding the classical P300 feature space on the classification performance of data collected from a P300 speller paradigm . Using stepwise linear discriminant analysis (SWLDA) to construct a classifier, the effects of spatial channel selection, channel referencing, data decimation, and maximum number of model features are compared with the intent of establishing a baseline for not only for the SWLDA classifier, but for related P300 speller classification methods in general. By supplementing the classical P300 recording locations with posterior locations, online classification performance of P300 speller responses can be significantly improved using SWLDA and the favorable parameters derived from the offline comparative analysis.

2008, Child and Adolescent Psychiatric Clinics of North America

2010, Journal of Neuroscience Methods

1992, Journal of Neuroscience Methods

2014

Background: We briefly describe the Psychology Experiment Building Language (PEBL), an open source software system for designing and running psychological experiments. New method: We describe the PEBL Test Battery, a set of approximately 70 behavioral tests which can be freely used, shared, and modified. Included is a comprehensive set of past research upon which tests in the battery are based. Results: We report the results of benchmark tests that establish the timing precision of PEBL. Comparison with existing method: We consider alternatives to the PEBL system and battery tests. Conclusions: We conclude with a discussion of the ethical factors involved in the open source testing movement.

2005, Journal of neuroscience methods

This paper describes the application of adaptive neuro-fuzzy inference system (ANFIS) model for classification of electroencephalogram (EEG) signals. Decision making was performed in two stages: feature extraction using the wavelet transform (WT) and the ANFIS trained with the backpropagation gradient descent method in combination with the least squares method. Five types of EEG signals were used as input patterns of the five ANFIS classifiers. To improve diagnostic accuracy, the sixth ANFIS classifier (combining ANFIS) was trained using the outputs of the five ANFIS classifiers as input data. The proposed ANFIS model combined the neural network adaptive capabilities and the fuzzy logic qualitative approach. Some conclusions concerning the saliency of features on classification of the EEG signals were obtained through analysis of the ANFIS. The performance of the ANFIS model was evaluated in terms of training performance and classification accuracies and the results confirmed that the proposed ANFIS model has potential in classifying the EEG signals.

1981, Analytical Biochemistry

1982, Journal of Neuroscience Methods

Radiohistochemical methods utilized to label drug and neurotransmitter receptors in vitro at the light microscopic level are quantitative. In this report, the response of tritium-sensitive sheet film ([~H]Ultrofilm) was characterized under conditions used for the light microscopic localization of neurotransmitter receptors by in vitro autoradiographic techniques. Radioactive standards containing varying concentrations of tritium were prepared from brain tissue and exposed to [3H]Uhrofilm for varying lengths of time, and the response of the film was measured by microdensitometry. A In optical density versus In radioactivity plot provided a useful linear relationship. Relationships established between radioactivity concentrations, exposure times and optical density were utilized to establish appropriate exposure conditions for several [3H]ligands in brain sections. The accuracy and pharmacological relevance of these methods were tested by studying the regional distribution of multiple benzodiazepine (BZ) receptors, and by analyzing the inhibitory potency of the triazolopyridazine, CL218,872, and methyl-beta-carbolinecarboxylate, two agents which discriminate between type 1 and type 2 BZ receptors. The results obtained compared favorably with results previously obtained in tissue homogenates by biochemical methods.

1987, Journal of Neuroscience Methods

A histochemical method for staining CNS zinc by the stoichiometric formation of zinc:quinoline fluorescent chelates is described. Four congeners of quinoline have been tested, and two found to be useful for histochemistry. The procedure is a one-step staining method, suitable for fresh-frozen and fixed tissue sections alike. The quinoline fluorescence selectively labels the CNS regions (such as hippocampus, amygdala) shown by prior histochemical procedures to be rich in histochemically reactive zinc in axon boutons and therefore appears to be a specific marker for the bouton zinc. Microfluorometric data indicate that the fluorochrome can be used for quantitative estimates of CNS zinc pools as well as qualitative studies of localization.

2008, Journal of Neuroscience Methods

Machine learning methods are an excellent choice for compensating the high variability in EEG when analyzing single-trial data in real-time. This paper briefly reviews preprocessing and classification techniques for efficient EEG-based brain-computer interfacing (BCI) and mental state monitoring applications. More specifically, this paper gives an outline of the Berlin brain-computer interface (BBCI), which can be operated with minimal subject training. Also, spelling with the novel BBCI-based Hex-o-Spell text entry system, which gains communication speeds of 6-8 letters per minute, is discussed. Finally the results of a real-time arousal monitoring experiment are presented.

2015, Journal of neuroscience methods

Electroencephalographic data are easily contaminated by signals of non-neural origin. Independent component analysis (ICA) can help correct EEG data for such artifacts. Artifact independent components (ICs) can be identified by experts via visual inspection. But artifact features are sometimes ambiguous or difficult to notice, and even experts may disagree about how to categorise a particular component. It is therefore important to inform users on artifact properties, and give them the opportunity to intervene. Here we first describe artifacts captured by ICA. We review current methods to automatically select artifactual components for rejection, and introduce the SASICA software, implementing several novel selection algorithms as well as two previously described automated methods (ADJUST, Mognon et al. Psychophysiology 2011;48(2):229; and FASTER, Nolan et al. J Neurosci Methods 2010;48(1):152). We evaluate these algorithms by comparing selections suggested by SASICA and other metho...

1986, Journal of Neuroscience Methods

A method is described for the isolation of neurons from defined regions of the mammalian central nervous system, by a combination of mechanical and enzymatic means. The procedure liberates neurons free of cellular debris and glial investments, allowing the formation of giga-ohm seals with patch clamp electrodes. The characteristic morphology of neurons is maintained, together with the diversity of active channels evident in the intact nervous system.

2008, Journal of Neuroscience Methods

The endovascular perforation rodent model for experimental subarachnoid hemorrhage (SAH) studies is criticized for lack of control over bleeding. Presently, there is no practical grading system to categorize the severity of SAH depending on the amount of blood. We outline a simple and objective novel SAH grading system by examining the subarachnoid blood clots in the basal-cisterns, and evaluate for correlation with neurological status and cerebral vasospasm. Effects of simvastatin, known to reduce vasospasm, were examined using this grading system. Seventy-seven adult male Sprague-Dawley rats were divided randomly into 3 groups: sham-operated (n=24), SAH (n=32), and SAH+simvastatin (n=25). High resolution brain pictures were used to grade the severity of SAH and categorize animals into mild, moderate and severe groups. The SAH grades were compared with neurological scores and internal-carotid artery parameters such as diameter, perimeter and wallthickness at 24hrs. Two investigators verified the grading system independently. The SAH grade showed linear correlation functionally with neurological status (r=0.42, p<0.01) and morphometrically with the degree of vasospasm (lrl>0.7, p<0.01), and also between two independent investigators (r=0.937, p<0.001). Simvastatin improved neurological score in moderate and severe (p<0.05) but not mild SAH groups (p=0.28). This grading system has the potential to be adopted for SAH experimental rodent models.

2008, Journal of Neuroscience Methods

Examination of spontaneous intrinsic brain activity is drawing increasing interest, thus methods for such analyses are rapidly evolving. Here we describe a novel measure, "network homogeneity", that allows for assessment of cohesiveness within a specified functional network, and apply it to resting-state fMRI data from adult ADHD and control participants. We examined the default mode network, a medial-wall based network characterized by high baseline activity that decreases during attention-demanding cognitive tasks. We found reduced network homogeneity within the default mode network in ADHD subjects compared to age-matched controls, particularly between the precuneus and other default mode network regions. This confirms previously published results using seed-based functional connectivity measures, and provides further evidence that altered precuneus connectivity is involved in the neuropathology of ADHD. Network homogeneity provides a potential alternative method for assessing functional connectivity of specific large-scale networks in clinical populations.

2001, Journal of Neuroscience Methods

Light scattering by tissue limits the imaging depth of two-photon microscopy and its use for functional brain imaging in vivo. We investigate the influence of scattering on both fluorescence excitation and collection, and identify tissue and instrument parameters that limit the imaging depth in the brain. (i) In brain slices, we measured that the scattering length at u= 800 nm is a factor 2 higher in juvenile cortical tissue (P14-P18) than in adult tissue (P90). (ii) In a detection geometry typical for in vivo imaging, we show that the collected fraction of fluorescence drops at large depths, and that it is proportional to the square of the effective angular acceptance of the detection optics. Matching the angular acceptance of the microscope to that of the objective lens can result in a gain of 3 in collection efficiency at large depths ( \ 500 mm). A low-magnification (20 ×), high-numerical aperture objective (0.95) further increases fluorescence collection by a factor of 10 compared with a standard 60 × -63× objective without compromising the resolution. This improvement should allow fluorescence measurements related to neuronal or vascular brain activity at \100 mm deeper than with standard objectives.

1994, Journal of Neuroscience …

1996, Journal of Neuroscience Methods

Neuronal noise sources and systematic variability in the shape of a spike limit the ability to sort multiple unit waveforms recorded from nervous tissue into their single neuron constituents. Here we present a procedure to efficiently sort spikes in the presence of noise that is anisotropic, i.e., dominated by particular frequencies, and whose amplitude distribution may be non-Gaussian, such as occurs when spike waveforms are a function of interspike interval. Our algorithm uses a hierarchical clustering scheme. First, multiple unit records are sorted into an overly large number of clusters by recursive bisection. Second, these clusters are progressively aggregated into a minimal set of putative single units based on both similarities of spike shape as well as the statistics of spike arrival times, such as imposed by the refractory period. We apply the algorithm to waveforms recorded with chronically implanted micro-wire stereotrodes from neocortex of behaving rat. Natural extensions of the algorithm may be used to cluster spike waveforms from records with many input channels, such as those obtained with tetrodes and multiple site optical techniques.

2010, Journal of Neuroscience Methods

There is increased need for efficient computerized methods to collect reliable data on a range of cognitive domains that can be linked to specific brain systems. Such need arises in functional neuroimaging studies, where individual... more

1979, Journal of Neuroscience Methods

Microelectrodes using single carbon fibres as the conducting element have been used since 1979 for electrophysiological measurements in vivo and in vitro. However, there is still considerable discussion about the manufacture of these electrodes, and no overall agreement as to the best way to minimise electrode noise. In this article we describe some revised methods for carbon fibre electrode manufacture, which we believe, gives the lowest noise performance for spike recording in vivo.

2012, Journal of Neuroscience Methods

The aim of connectomics is to provide a comprehensive description of the complete structural connectivity of the entire brain (http://www.scholarpedia.org/article/Connectome). Given that such a description at the ultimate resolution of single cells is currently infeasible, one needs to adopt a multi-scale approach. At the level of the entire brain diffusion MRI represents a particularly interesting experimental avenue for in-vivo as well as ex-vivo studies. Very recently, we have used a methodology combining landmark-based registration and automatic cortical parcellation to build high resolution normalized connection networks [1] which has led to a detailed characterization of the human brain structural network [2]. In the present abstract we have extended this work by proposing a hierarchical parcellation scheme of the cerebral cortex in order to map the connection network of the brain at multiple scales. The motivation was not only to provide the end user with wiring maps corresponding to the scale needed for a specific application but also to ask whether network architectures at different scales would differ in the way they are organized. The latter finding would cast doubt on the generality across scales of any attempt to characterize cortical networks with the methods described in the present paper.

2008, Journal of Neuroscience Methods

Brain–computer interfaces (BCIs) translate brain activity into signals controlling external devices. BCIs based on visual stimuli can maintain communication in severely paralyzed patients, but only if intact vision is available. Debilitating neurological disorders however, may lead to loss of intact vision. The current study explores the feasibility of an auditory BCI. Sixteen healthy volunteers participated in three training sessions consisting of 30 2–3 min runs in which they learned to increase or decrease the amplitude of sensorimotor rhythms (SMR) of the EEG. Half of the participants were presented with visual and half with auditory feedback. Mood and motivation were assessed prior to each session.Although BCI performance in the visual feedback group was superior to the auditory feedback group there was no difference in performance at the end of the third session. Participants in the auditory feedback group learned slower, but four out of eight reached an accuracy of over 70% correct in the last session comparable to the visual feedback group. Decreasing performance of some participants in the visual feedback group is related to mood and motivation. We conclude that with sufficient training time an auditory BCI may be as efficient as a visual BCI. Mood and motivation play a role in learning to use a BCI.

2010, Journal of Neuroscience Methods

About 1% of the people in the world suffer from epilepsy. The main characteristic of epilepsy is the recurrent seizures. Careful analysis of the electroencephalogram (EEG) recordings can provide valuable information for understanding the mechanisms behind epileptic disorders. Since epileptic seizures occur irregularly and unpredictably, automatic seizure detection in EEG recordings is highly required. Wavelet transform (WT) is an effective analysis tool for non-stationary signals, such as EEGs. The line length feature reflects the waveform dimensionality changes and is a measure sensitive to variation of the signal amplitude and frequency. This paper presents a novel method for automatic epileptic seizure detection, which uses line length features based on wavelet transform multiresolution decomposition and combines with an artificial neural network (ANN) to classify the EEG signals regarding the existence of seizure or not. To the knowledge of the authors, there exists no similar work in the literature. A famous public dataset was used to evaluate the proposed method. The high accuracy obtained for three different classification problems testified the great success of the method.

2007, Journal of Neuroscience Methods

Synesthesia is an unusual condition in which stimulation of one modality evokes sensation or experience in another modality. Although discussed in the literature well over a century ago, synesthesia slipped out of the scientific spotlight for decades because of the difficulty in verifying and quantifying private perceptual experiences. In recent years, the study of synesthesia has enjoyed a renaissance due to the introduction of tests that demonstrate the reality of the condition, its automatic and involuntary nature, and its measurable perceptual consequences. However, while several research groups now study synesthesia, there is no single protocol for comparing, contrasting and pooling synesthetic subjects across these groups. There is no standard battery of tests, no quantifiable scoring system, and no standard phrasing of questions. Additionally, the tests that exist offer no means for data comparison. To remedy this deficit we have devised the Synesthesia Battery. This unified collection of tests is freely accessible online (http://www.synesthete.org). It consists of a questionnaire and several online software programs, and test results are immediately available for use by synesthetes and invited researchers. Performance on the tests is quantified with a standard scoring system. We introduce several novel tests here, and offer the software for running the tests. By presenting standardized procedures for testing and comparing subjects, this endeavor hopes to speed scientific progress in synesthesia research.

1999, Journal of Neuroscience Methods

The neurochip is a silicon micromachined device upon which cultured mammalian neurons can be continuously and individually monitored and stimulated. The neurochip is based upon a 4×4 array of metal electrodes, each of which has a caged well structure designed to hold a single mature cell body while permitting normal outgrowth of neural processes. We demonstrate that this device is capable of maintaining cell survival, and that the electrodes can both record and stimulate electrical activity in individual cells with no crosstalk between channels.

2008, Journal of neuroscience …

Electrocorticographic (ECoG) signals have been shown to contain reliable information about the direction of arm movements and can be used for on-line cursor control. These findings indicate that the ECoG is a potential basis for a brain-machine interface (BMI) for application in paralyzed patients. However, previous approaches to ECoG-BMIs were either based on classification of different movement patterns or on a voluntary modulation of spectral features. For a continuous multi-dimensional BMI control, the prediction of complete movement trajectories, as it has already been shown for spike data and local field potentials (LFPs), would be a desirable addition for the ECoG, too. Here, we examined ECoG signals from six subjects with subdurally implanted ECoG-electrodes during continuous two-dimensional arm movements between random target positions. Our results show that continuous trajectories of 2D hand position can be approximately predicted from the ECoG recorded from hand/arm motor cortex. This indicates that ECoG signals, related to body movements, can directly be transferred to equivalent controls of an external effector for continuous BMI control.

1987, Journal of Neuroscience Methods

Recently developed in vitro preparations of the brainstem-spinal cord from neonatal rat suitable for investigation of motor control systems for mammalian locomotion and respiration are described. The preparations remain viable for extended periods under standard in vitro conditions and generate rhythmic motor patterns for locomotion and respiration. The methodology of the preparations and characteristics of the motor output patterns are described. The preparations retain functional circuitry for major components of the motor control systems, including brainstem respiratory and spinal locomotor pattern generating networks, brainstem locomotor command regions, descending bulbospinal and ascending spinal pathways, and mechanosensory afferent input systems. They therefore offer potential for investigation of diverse aspects of the mammalian respiratory and locomotor control systems.

2000, Journal of Neuroscience Methods

Biotinylated dextran amines (BDA) are highly sensitive tools for anterograde and retrograde pathway tracing studies of the nervous system. BDA can be reliably delivered into the nervous system by iontophoretic or pressure injection and visualized with an avidin-biotinylated HRP (ABC) procedure, followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. High molecular weight BDA (10 k) yields sensitive and exquisitely detailed labeling of axons and terminals, while low molecular weight BDA (3 k) yields sensitive and detailed retrograde labeling of neuronal cell bodies. The detail of neuronal cell body labeling can be Golgi-like. BDA tolerates EM fixation and processing well and can, therefore, be readily used in ultrastructural studies. Additionally, BDA can be combined with other anterograde or retrograde tracers (e.g. PHA-L or cholera toxin B fragment) and visualized either by multi-color DAB multiple-labeling -if permanent labels are desired, or by using multiple simultaneous immunofluorescence -if fluorescence viewing is desired. In the same manner, BDA pathway tracing and neurotransmitter immunolabeling can be combined. Note that BDA pathway tracing can also be combined with anterograde or retrograde labeling with fluorescent dextran amines, if one wishes to exclusively use tracers with the favorable transport properties and sensitivities of dextran amines. In this case, the BDA can be visualized together with the fluorescent dextran amines using fluorescence labeling for the BDA, or the fluorescent dextran amines can be visualized together with the BDA by multicolor DAB labeling via immunolabeling of the fluorescent dextran amines using anti-fluorophore antisera. BDA is, thus, a flexible and valuable pathway tracing tool that has gained widespread popularity in recent years.

2002, Journal of Neuroscience Methods

The mouse is an excellent model for investigations of stroke and neural injury. However, there is a paucity of long term functional outcome measurements for the mouse. We, therefore, developed a sensorimotor functional test (corner test) and applied this test to a model of focal cerebral ischemia in the mouse. Male C57/6J mice (n=20) were subjected to embolic middle cerebral

2008, Journal of Neuroscience Methods

The Hoffmann (or H) reflex is considered a major probe for non-invasive study of sensorimotor integration and plasticity of the central nervous system in humans. The first section of this paper reviews the neurophysiological properties of the H-reflex, which if ignored create serious pitfalls in human experimental studies. The second section reviews the spinal inhibitory circuits and neuronal pathways that can be indirectly assessed in humans using the H-reflex. The most confounding factor is that reciprocal, presynaptic, and Ib inhibition do not act in isolation during movement. Therefore, characterization of these spinal circuits should be more comprehensive, especially in cases of a neurological injury because neurophysiological findings are critical for the development of successful rehabilitation protocols. To conclude, the H-reflex is a highly sensitive reflex with an amplitude that is the result of complex neural mechanisms that act synchronously. If these limitations are recognized and addressed, the H-reflex constitutes one of the major probes to assess excitability of interneuronal circuits at rest and during movement in humans.

2010, Journal of neuroscience methods

Artifacts in functional magnetic resonance imaging (fMRI) data, primarily those related to motion and physiological sources, negatively impact the functional signal-to-noise ratio in fMRI studies, even after conventional fMRI preprocessing. Independent component analysis’ demonstrated capacity to separate sources of neural signal, structured noise, and random noise into separate components might be utilized in improved procedures to remove artifacts from fMRI data. Such procedures require a method for labeling independent components (ICs) as representing artifacts to be removed or neural signals of interest to be spared. Visual inspection is often considered an accurate method for such labeling as well as a standard to which automated labeling methods are compared. However, detailed descriptions of methods for visual inspection of ICs are lacking in the literature. Here we describe the details of, and the rationale for, an operationalized fMRI data denoising procedure that involves visual inspection of ICs (96% inter-rater agreement). We estimate that dozens of subjects/sessions can be processed within a few hours using the described method of visual inspection. Our hope is that continued scientific discussion of and testing of visual inspection methods will lead to the development of improved, cost-effective fMRI denoising procedures.

1999, Journal of Neuroscience Methods

This paper illustrates the use of the recently introduced method of partial directed coherence in approaching how interactions among neural structures change over short time spans that characterize well defined behavioral states. Central to the method is its use of multivariate time series modelling in conjunction with the concept of Granger causality. Simulated neural network models were used to illustrate the technique's power and limitations when dealing with neural spiking data. This was followed by the analysis of multi-unit activity data illustrating dynamical change in the interaction of thalamo-cortical structures in a behaving rat.

2003, Journal of Neuroscience Methods

A modification of directed transfer function */direct DTF */is proposed for the analysis of direct information transfer among brain structures on the basis of local field potentials (LFP). Comparison of results obtained by the analysis of simulated and experimental data with a new dDTF and DTF method is shown. A new measure to estimate direct causal relations between signals is defined. The present results demonstrate the effectiveness of the new dDTF method and indicate that the dDTF method can be used to obtain the reliable patterns of connections between various brain structures. #

2006, Journal of Neuroscience Methods

A new method for estimation of current-source density (CSD) from local field potentials is presented. This inverse CSD (iCSD) method is based on explicit inversion of the electrostatic forward solution and can be applied to data from multielectrode arrays with various geometries. Here, the method is applied to linear-array (laminar) electrode data. Three iCSD methods are considered: the CSD is assumed to have cylindrical symmetry and be (i) localized in infinitely thin discs, (ii) step-wise constant or (iii) continuous and smoothly varying (using cubic splines) in the vertical direction. For spatially confined CSD distributions the standard CSD method, involving a discrete double derivative, is seen in model calculations to give significant estimation errors when the lateral source dimension is comparable to the size of a cortical column (less than ∼1 mm). Further, discontinuities in the extracellular conductivity are seen to potentially give sizable errors for even wider source distributions. The iCSD methods are seen to give excellent estimates when the correct lateral source dimension and spatial distribution of conductivity are incorporated. To illustrate the application to real data, iCSD estimates of stimulus-evoked responses measured with laminar electrodes in the rat somatosensory (barrel) cortex are compared to estimates from the standard CSD method.

2010, Journal of Neuroscience Methods

Quantification of endogenous brain-derived neurotrophic factor (BDNF) can be performed with an enzyme-linked immunosorbent assay (ELISA). Although BDNF has been determined in blood and brain preparations in numerous studies with ELISA kits, the methodological issues regarding measurements of BDNF concentrations in the blood and particularly in the brain have only been superficially investigated. We aimed at validating and optimizing the BDNF ELISA kit with respect to measurements in rat blood and brain samples. We found that the pre-analytical conditions were critical for plasma samples, but not serum or whole blood samples. The intra-and inter-assay variation and the accuracy and yield of the BDNF ELISA kit in rat serum and brain tissue were conducted with the optimal dilutions of frontal cortex and hippocampus extract. The optimal dilutions of frontal cortex and hippocampus extracts were determined to be 20 and 120 times, and we established that the intra-assay coefficient of variation (CV%) was 8 in hippocampus and 2 in frontal cortex and serum. The inter-assay variation was also low with a CV% of 11 or less in hippocampus, frontal cortex, and serum. Finally, we found that the accuracy and yield of the BDNF measurements were high in serum and low in hippocampus and frontal cortex. We conclude that the BDNF ELISA kit determines serum BDNF accurately and with high reproducibility. Furthermore it can be used for measurement of BDNF in rat brain preparations when particular precautions are taken and in particular with care regarding the dilution of the brain tissue samples.

2012, Journal of neuroscience methods

The development of various neuroimaging techniques is rapidly improving the measurements of brain function/structure. However, despite improvements in individual modalities, it is becoming increasingly clear that the most effective research approaches will utilize multi-modal fusion, which takes advantage of the fact that each modality provides a limited view of the brain. The goal of multi-modal fusion is to capitalize on the strength of each modality in a joint analysis, rather than a separate analysis of each. This is a more complicated endeavor that must be approached more carefully and efficient methods should be developed to draw generalized and valid conclusions from high dimensional data with a limited number of subjects. Numerous research efforts have been reported in the field based on various statistical approaches, e.g. independent component analysis (ICA), canonical correlation analysis (CCA) and partial least squares (PLS). In this review paper, we survey a number of multivariate methods appearing in previous multimodal fusion reports, mostly fMRI with other modality, which were performed with or without prior information. A table for comparing optimization assumptions, purpose of the analysis, the need of priors, dimension reduction strategies and input data types is provided, which may serve as a valuable reference that helps readers understand the trade-offs of the 7 methods comprehensively. Finally, we evaluate 3 representative methods via simulation and give some suggestions on how to select an appropriate method based on a given research.

2006, Journal of Neuroscience Methods

One major challenge in neuroscience is the identification of interrelations between signals reflecting neural activity. When applying multivariate time series analysis techniques to neural signals, detection of directed relationships, which can be described in terms of Granger-causality, is of particular interest. Partial directed coherence has been introduced for a frequency domain analysis of linear Granger-causality based on modeling the underlying dynamics by vector autoregressive processes. We discuss the statistical properties of estimates for partial directed coherence and propose a significance level for testing for nonzero partial directed coherence at a given frequency. The performance of this test is illustrated by means of linear and non-linear model systems and in an application to electroencephalography and electromyography data recorded from a patient suffering from essential tremor.

2006, Journal of Neuroscience Methods

2002, Journal of Neuroscience Methods

We have developed a simple and expandable procedure for classification and validation of extracellular data based on a probabilistic model of data generation. This approach relies on an empirical characterization of the recording noise. We first use this noise characterization to optimize the clustering of recorded events into putative neurons. As a second step, we use the noise model again to assess the quality of each cluster by comparing the within-cluster variability to that of the noise. This second step can be performed independently of the clustering algorithm used, and it provides the user with quantitative as well as visual tests of the quality of the classification. #

2005, Journal of Neuroscience Methods

This paper describes an interactive computer program for decomposing EMG signals into their component motor-unit potential (MUP) trains and for averaging MUP waveforms. The program is able to handle single-or multi-channel signals recorded by needle or fine-wire electrodes during low and moderate levels of muscular contraction. It includes advanced algorithms for template matching, resolving superimpositions, and waveform averaging, as well as a convenient user interface for manually editing and verifying the results. The program also provides the ability to inspect the discharges of individual motor units more closely by subtracting out interfering activity from other MUP trains. Decomposition accuracy was assessed by cross-checking pairs of signals recorded by nearby electrodes during the same contraction. The results show that 100% accuracy can be achieved for MUPs with peak-to-peak amplitudes greater than 2.5 times the rms signal amplitude. Examples are presented to show how decomposition can be used to investigate motor-unit recruitment and discharge behavior, to study motor-unit architecture, and to detect action potential blocking in doubly innervated muscle fibers.