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E G Butler

Publications and source records attributed to E G Butler.

At least 19 recordsLinked to original sources

Automatic detection of bursts in spike trains recorded from the thalamus of a monkey performing wrist movements.

In a previous paper (Churchward PR, Butler EG, Finkelstein DI, Aumann TD, Sudbury A, Horne MK. J Neurosci Methods 1997;76:203-210), we showed that a simple back propagation neural network could reliably model visual inspection by human observers in detecting the point of change of neuronal discharge patterns. The data for that study was deliberately chosen so that the point of change was readily detected and there would be high concordance between human observers. We wished to extend this investigation by comparing a variety of automatic analysis methods on more complex data sets. Two automatic analysis methods have been discussed in this paper. The knowledge based spike train analysis (KBSTA) was designed to emulate the detection of bursts by human observers. The self-organizing feature map (SOFM) spike train analysis determined a burst by classifying the patterns of neuronal discharge. Neuronal discharge was recorded from the motor thalamus and nucleus ventralis posterior lateralis caudalis (VPLc) of a monkey performing consecutive trials of skilled wrist movements. Recordings were made from 36 neurons whose discharge patterns were related to wrist movement. Three hundred and sixty trials performed during the recording of these 36 neurons were chosen at random and used to compare the three methods, KBSTA, SOFM, and visual inspection. The main results of this study show that for the 360 trials the three detection methods have very similar results in detecting the onset and offset of neuronal bursts. The SOFM method is not the best first approach for detecting a burst, but it does provides independent evidence to support the KBSTA and visual inspection methods. In conclusion we propose the KBSTA method as a practical, automatic technique to identify bursts of neuronal discharge.

Action Potentials↗

Neuronal activity in the monkey ventrolateral thalamus following perturbations of voluntary wrist movements.

Extracellular single-cell recordings were made from the cerebellar thalamus (89 neurones) and the VPLc (53 neurones) of three conscious monkeys. The animals were trained to perform wrist movement paradigms including: (a) visually triggered skilled, voluntary movements; (b) 100-ms duration torque pulse perturbations applied during a hold period (termed Pa perturbations); (c) 100-ms perturbations that commenced 100 ms after the visual trigger but during preparation before a skilled, voluntary movement (termed Pb perturbations); and (d) 100-ms perturbations during the skilled, voluntary movement (termed Pm perturbations). These Pb and Pm perturbations were used to identify central and peripheral influences on patterns of neuronal discharge in the ventrolateral thalamus. There was no systematic difference between the responses to Pb and Pm perturbations of neurones in the cerebellar thalamus and those in VPLc. The responses of VPLc and cerebellar thalamic neurones to Pa perturbations were considered to represent transduction of peripheral afferent input, and these responses were compared with the responses to the other types of perturbations. Up to 40% of neurones in cerebellar thalamus and VPLc responded to Pb and Pm perturbations in a similar pattern to that which followed Pa perturbations, and therefore most likely represented faithful transduction of peripheral input. However, the response of over half the neurones in VPLc and cerebellar thalamus to Pb or Pm perturbations differed from Pa perturbations in a manner suggesting that central influences had gated the peripheral input. The short-latency response in cerebellar thalamus which was modified by central influences is appropriately timed to contribute to the "intended" response to perturbations of motor cortical neurones.

Afferent Pathways↗

A comparison of methods used to detect changes in neuronal discharge patterns.

The discharge pattern of two thalamic neurones was recorded from a conscious monkey performing voluntary movements about the wrist joint. The neuronal discharge was displayed as a raster centred on movement of the wrist. The discharge patterns of both neurones was very strongly correlated with movement. Three experienced researchers were asked to examine the data and to classify every part of each trial as background discharge, 'on' (increased firing rate) or 'off' (decreased or zero firing rate) and to mark the times that neuronal discharge changed state. A 'standard output' was made from these classifications. A back-propagation artificial Neural Network (the Network) was used to model the standard output and cumulative sums (CUSUMs) and maximum likelihood was then performed on the data and compared with the Network. There was a high correlation between the output of each observer (r > 0.61) and the standard output and between the Network and the standard output (r > 0.99). However the correlation between standard output and CUSUMs (r = 0.06) and standard output and maximum likelihood (r = 0.36) was much lower. The Network could be trained with as few as 12 trials, indicating a high degree of constancy in the methods employed by the observers. The Network was also highly efficient at detecting changes in state of neuronal activity (r > 0.99). In summary, when used on single trial data, visual inspection is a reliable method for detecting timing of change neuronal discharge and is superior to CUSUM and maximum likelihood. As well it is capable of detecting neuronal discharge state: that is whether firing rate is increased, normal or decreased. Neural Networks promise to be a useful method of confirming the consistency of visual inspection as a means of detecting changes in neuronal discharge pattern.

Action Potentials↗

The relationship between monkey ventrolateral thalamic nucleus activity and kinematic parameters of wrist movement.

Extracellular recordings were made from single neurones in the cerebellar thalamus (75 neurones) and the VPLc (44 neurones) of four conscious moving monkeys. The experiment was designed to establish the discharge of ventrolateral thalamic neurones encodes information about kinematic parameters. The animals were trained to resist unexpected perturbations of the wrist and to perform skilled, voluntary wrist movements, producing stereotyped reflex and active movements with a wide range of durations and amplitudes. Statistical analysis of the discharge pattern associated with individual trials of movement was performed. In various maintained wrist positions there was a significant correlation (P < 0.05) between frequency of tonic discharge and joint position in 40% of the cerebellar thalamic neurones and in 54% of VPLc neurones. The phasic neuronal discharge associated with stereotyped movement often appeared "velocity-or acceleration-like'. However, statistical analyses revealed that the phasic discharge of only a small percentage of cerebellar thalamic and VPLc neurones was correlated with duration of movement, peak velocity or acceleration. The percentage of cerebellar thalamic neurones with discharge correlated to kinematic parameters was much greater when an unexpected change in the gain between joint angle and screen display led to errors in tracking the target. It is concluded that the cerebello-thalamo-cortical (CTC) pathway, carries information regarding maintained joint position but not velocity or acceleration of movement during a stereotyped task. However, the CTC pathway has a greater capacity to signal information about movement velocity and acceleration when there is a mismatch between the intended and actual movement.

Animals↗

Tactical combat casualty care in special operations.

U.S military medical personnel are currently trained to care for combat casualties using the principles taught in the Advanced Trauma Life Support (ATLS) course. The appropriateness of many of the measures taught in ATLS for the combat setting is unproven. A 2-year study to review this issue has been sponsored by the United States Special Operations Command. This paper presents the results of that study. We will review some of the factors that must be considered in caring for wounded patients on the battlefield with an emphasis on the Special Operations environment. A basic management protocol is proposed that organizes combat casualty care into three phases and suggests appropriate measures for each phase. A scenario-based approach is needed to plan in more detail for casualties on specific Special Operations missions, and several sample scenarios are presented and discussed.

Airway Obstruction↗

The role of the cerebello-thalamo-cortical pathway in skilled movement.

Studies of lesions of the primate cerebellum leave little doubt that the cerebellum is necessary for the execution of smooth and accurate movements. How the cerebellum fulfills this role at a neuronal level remains unknown. It is likely that the cerebellum exerts the same effect on a number of different efferent targets. In order to influence voluntary movement, a major output from the cerebellum projects to the motor cortex via the cerebello-thalamo-cortical (CTC) pathway. By examining neuronal activity in the cerebellar thalamus, and comparing this with activity recorded from its connections with the deep cerebellar nuclei and motor cortex, conclusions can be made regarding cerebellar function. Current data does not support a role for the CTC pathway in the initiation of movement or the control of trans-cortical reflexes. Also, the evidence does not support the hypothesis that the cerebellum prevents terminal movement oscillations by predictively sending a message to the antagonist muscle to brake the movement. The available literature supports the Eccles theory that during normal movement, the CTC pathway receives a form of efference copy from the motor cortex and compares this message with that derived from peripheral afferents about the actual progress of the movement. However, there is not a significant degree of kinematic information passing through this pathway in the course of a voluntary movement. Therefore the actual site of comparison or error-detection in this system awaits further elucidation.

Animals↗

Neural activity in the monkey anterior ventrolateral thalamus during trained, ballistic movements.

1. To examine the role of the anterior ventrolateral thalamic nucleus (VLa) in motor control, extracellular single-cell recordings were made from the VLa nucleus in three conscious monkeys performing visually triggered, rapid movements requiring flexion and extension of the wrist joint. The movement paradigms consisted of three components: an initial hold period, a ballistic movement, and a final hold period. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurons receiving input from the cerebellum. Neurons subsequently confirmed histologically as lying within the VLa nucleus were located anterior to those "driven" by cerebellar stimulation. 3. The activities of 261 VLa neurons displaying movement-related behavior were examined. In the absence of movement, the activity of these neurons ranged from 5 to 80 spikes/s, the majority of cells (222/261; 85%) firing between 10 and 30 spikes/s. Neural activity was not influenced by afferent input from skin, joint, or muscle but altered markedly when the animal engaged in active movement. 4. The relationship between neural activity and movement at a specific joint was determined in 189 of the 261 neurons. The majority of these neurons (161/189; 85%) modulated their activity in response to movement confined to a single joint; the remaining neurons displayed multijoint motor responses, their activity being best related to a motor act, such as grasping, reaching, or feeding. There was no clear segregation in the representation of body parts in the VLa nucleus to suggest the presence of clearly defined somatotopy. 5. The activities of wrist-related neurons (45 of the 261) were examined to determine the motor characteristics of the VLa nucleus. Three distinctive activity patterns were exhibited by these neurons during the performance of the movement paradigms: 1) a phasic burst of < 300 ms in duration (34/45; 76%); 2) a sustained change in neural activity lasting > 300 ms (typically up to 1,000 ms; 4/45; 9%); and 3) both a phasic and a sustained response, the sustained response occurring either prior or subsequent to the phasic response (7/45; 15%). 6. The movement-related activity of the wrist-related neurons occurred late, 52% firing after the onset of the forearm electromyogram (EMG). In 47% of the neurons, discharge rate was related to movement direction and, in a smaller proportion (13%), joint position. No relationship was found between neural activity patterns and amplitude of movement or velocity of movement. (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Sensory characteristics of monkey thalamic and motor cortex neurones.

1. Extracellular single-cell recordings were made from the cerebellar thalamus, the ventro-posterior lateralis par caudalis (VPLc) and motor cortex of three conscious monkeys. Recordings were made from the thalamus as well as the cortex in two monkeys. In all, recordings were made from the thalamus in four hemispheres and from the motor cortex in four hemispheres. The animals were trained to permit a detailed examination when relaxed. Unexpected perturbations were applied to the wrist. Seventy-seven wrist-related neurones were recorded in the cerebellar thalamus, forty-two neurones from the VPLc and eighty-four neurones in motor cortex. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurones receiving input from the cerebellum. The location of all neurones was verified histologically. 3. The majority of cerebellar thalamic neurones had deep sensory receptive fields related to a single muscle, a group of synergists or a single joint. There was a distinct topographical organization. These fields were similar to sensory fields in motor cortical neurones, but had higher thresholds. 4. VPLc neurones had discrete deep or cutaneous sensory fields, or a combination of these fields, which suggests convergence. VPLc neurones had fields with lower thresholds than cerebellar thalamic neurones. The somatotopically located forelimb area in the VPLc was posterior to and continuous with the forelimb area in the cerebellar thalamus. 5. VPLc neurones responded with a shorter latency to wrist perturbations than did cerebellar thalamic neurones. VPLc neurones with deep sensory fields changed firing significantly earlier than those with cutaneous fields. The VPLc is likely to be the major source of sensory input to the motor cortex, and based on the results of this study we suggest that the VPLc is the thalamic nucleus best placed to transmit short-latency afferent input from the forelimb. 6. The timing of the neuronal discharge of cerebellar thalamic and VPLc cells, which resulted from perturbations of the wrist, was best linked to the duration of movement rather than its amplitude. The cells began firing as soon as the velocity changed sign and continued firing until the sign of the velocity changed again. In subsequent corrective movements neuronal discharge in the VPLc appeared to also encode movement acceleration.

Animals↗

The activity of monkey thalamic and motor cortical neurones in a skilled, ballistic movement.

1. Three monkeys were trained to perform a reaction-time task of the wrist and single-cell recordings were made from the motor cortex (eighty-four cells), ventro-posterior lateralis par caudalis (VPLc) (forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. The majority (43/77, 56%) of cerebellar thalamic neurones fired phasically during movement, whereas in the motor cortex most neurones (53/84, 64%) had a phasic-tonic discharge pattern. Most neurones in both locations discharged in relation to the direction of movement (reciprocal pattern). 3. The cerebellar thalamus is unlike the motor cortex in that it does not usually encode a signal for force or joint position in its discharge. 4. Twenty-two per cent (17/77) of cerebellar thalamic neurones had a period of reduced discharge rate before the phasic burst of activity, and represent a pattern of discharge not seen in motor cortex or VPLc neurones. 5. The onset of phasic activity in the cerebellar thalamus was significantly later (average 94 ms) than in the motor cortex but occurred just before electromyogram (EMG) activity. The phasic activity in the cerebellar thalamus usually ended before the phasic component of motor cortex discharge was completed. 6. Phasic activity in VPLc neurones commenced after the onset of EMG discharge and on average 26 ms after the commencement of movement. Most neurones with deep sensory receptive fields fired with a reciprocal pattern, while neurones with cutaneous fields usually fixed bidirectionally in relation to the task. Almost one-third of neurones signalled force and a similar number had discharge levels that encoded characteristics of the joint position. 7. The duration of discharge of VPLc neurones during the voluntary movement was marginally less than the duration of the movement velocity peak and the VPLc may therefore be signalling the duration of the velocity. Phasic activity in cerebellar thalamic neurones fired for a duration similar to the VPLc neurones, but commenced before the movement. Therefore, if the cerebellar thalamus is carrying information about the duration of the velocity, it does so before the movement starts. 8. The phasic burst of activity in cells of the cerebellar thalamus is timed so that it can contribute to the later component of the phasic burst of motor cortical discharge. Thus we speculate that in skilled, ballistic movements, the cerebellum may provide a response which travels via the cerebellar thalamus and helps to determine the magnitude and duration of the phasic part of cortical discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A frequency analysis of neuronal activity in monkey thalamus, motor cortex and electromyograms in wrist oscillations.

1. Extracellular recordings were made in three monkeys while recording from neurones in the motor cortex (eighty-four cells), ventro-posterior lateralis pars caudalis (VPLc, forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. This experiment was designed to produce active and reflex movements of varying velocities in order to study the relationship between amplitude of velocity and magnitude of neuronal discharge of thalamic neurones. The active movements were voluntary rapid alternating movements (RAMs) of the wrist and the reflex movements were produced by forcibly oscillating the wrist joint between frequencies of 1 and 7 Hz (forced oscillations). 3. This study was also designed to examine cerebellar influences on a reflex path, namely the transcortical reflex loop. Forced oscillations were predicted to provide circumstances where active damping was required to prevent excessive oscillations in the reflex path. Rapid alternating movements of the wrist were predicted to provide circumstances where oscillations at the natural frequency in that reflex path would support and propagate the movements. 4. Forced oscillations from 1 to 7 Hz produced movements of different velocities. VPLc and cerebellar thalamic neurones discharged in relation to the duration of movement in a particular direction, but their discharge levels were unrelated to the magnitude of the velocity. Motor cortex neurones fired in a pattern which was related to the timing but not the magnitude of the acceleration. 5. In forced oscillations of the wrist the resonant frequency was between 3 and 7 Hz. They may be controlled in part by a transcortical reflex. The cerebellar thalamic neurones did not fire before motor cortex neurones. Therefore, it is unlikely that the cerebello-thalamo-cortical pathway is necessary to damp these potentially unstable oscillations by an effect on antagonist-related cortical neurones. 6. Rapid alternating movements (RAMs) of monkeys' wrists were performed in a stereotyped fashion over a narrow range of frequencies with the greatest displacement in joint angle and peak velocity at the natural frequency of 3-5 Hz. 7. During the performance of RAMs, neuronal discharge modulated sinusoidally in the VPLc, cerebellar thalamus and motor cortex. There was no relationship between velocity and neuronal discharge of the cerebellar thalamic and motor cortical neurones but there did appear to be a relationship between velocity and VPLc neuronal discharge. 8. The onset of electromyogram (EMG) discharge changed earlier than neuronal discharge in the motor cortex and thalamus during the performance of RAMs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Toxicological studies on a benzofurane derivative. II. Demonstration of peroxisome proliferation in rat liver.

The uricosuric drug benzbromarone (3,5-dibromo-4-hydroxyphenyl)-1-(2-ethyl-3-benzofuranyl)methanone, a benzofurane derivative, was studied for its effects on parameters related to hepatic peroxisome proliferation. Groups of male F-344 rats were fed either basal diet, the peroxisome proliferator clofibrate at 5000 ppm as a comparison compound, or benzbromarone at two doses, 1000 and 2000 ppm. Benzbromarone and clofibrate produced hepatomegaly and increases in the activities of catalase, acyl CoA oxidase, malate dehydrogenase, and glycerol-3-phosphate dehydrogenase. Benzbromarone and clofibrate also both induced similar histologic and ultrastructural changes in hepatocytes, including induction of peroxisomes. Therefore, benzbromarone acted as a peroxisome-proliferating agent in rats under these conditions. Benzbromarone differs from other peroxisome proliferators in its chemical structure, uricosuric action, and the morphology of liver peroxisomes that were induced by exposure.

Animals↗

Intraventricular infusion of Dopamine in Parkinson's disease.

A patient with severe end-stage Parkinson's disease and troublesome fluctuations in motor function was treated with a long-term intraventricular infusion of dopamine. There was modest improvement in speech and mentation and there was smoother control of motor symptoms that was superior to that achieved by conventional oral medications.

Adult↗

Cerebral deposits of carcinoid tumour.

This report details a most unusual case of cystic cerebral metastasis. The patient developed symptoms due to carcinoid deposits in the brain. The clinical course has been protracted and the primary source of the carcinoid tumour remains unknown.

Brain↗

Obstructive hydrocephalus caused by multiple sclerosis.

A case is reported of obstructive hydrocephalus secondary to the mass effect of a plaque of acute demyelination in the brainstem. The literature on the CT scan appearances in multiple sclerosis is briefly discussed in relation to this case.

Adrenal Cortex Hormones↗

A semiautomated system for measurement of 96 simultaneous spectrophotometric enzyme assays.

A semiautomated system for spectrophotometric measurement of enzyme activity is described. In comparison to a 1-ml reaction volume monitored continuously by a conventional spectrophotometer, this system requires 1/10 to 1/100 the volume of sample, and 1/8 to 1/4 the time for measurement and computation of 96 enzyme assays. The system hardware consists of a 96-well platereader interfaced to a personal computer. Absorbances of 96 reactions are measured at timed intervals. These data are transmitted electronically from the platereader to the computer through the modem port using a modem program. The reaction rates are computed from the timed absorbance readings using a spreadsheet program. Three enzyme assays are presented, but the method has been used for several other assays and is applicable to many spectrophotometric rate assays. Many laboratories currently possess one or both of the two major components of the relatively inexpensive system described.

Animals↗

Induction of hepatic peroxisome proliferation in mice by lactofen, a diphenyl ether herbicide.

A technical grade of lactofen (1'[carboethoxy]ethyl 5-[2-chloro-4-[trifluoro-methyl] phenoxy]-2-nitrobenzoate) has been shown to induce liver tumors in mice. To determine a possible mechanism of action, the effect of exposure for 7 weeks to dietary concentrations of 2, 10, 50, and 250 ppm technical grade lactofen and 250 ppm of pure lactofen was studied for various liver parameters in groups of male and female CD-1 mice. Liver-weight to body-weight ratio, liver catalase, liver acyl-CoA oxidase, liver cell cytoplasmic eosinophilia, nuclear and cellular size, and peroxisomal staining were increased by the tumorigenic dose of lactofen, i.e., 250 ppm, in a fashion similar to the comparison chemical nafenopin (500 ppm), which is a peroxisome proliferator. Lower doses of lactofen that were reported as nontumorigenic had little or no effect on these parameters. Thus, pure and technical grade lactofen appear to induce murine liver tumors through a mechanism similar to epigenetic hepatocarcinogens of the peroxisome proliferating type.

Acyl-CoA Oxidase↗

Genetic differences in enzymes associated with peroxisome proliferation and hydrogen peroxide metabolism in inbred mouse strains.

Enzyme activities relating to H2O2 production (peroxisomal acyl-CoA oxidase) and degradation (catalase and glutathione peroxidase) were measured in the livers of male mice of the inbred strains C57BL/6J (C57) and C3H/HeJ (C3H) and their F1 hybrid, B6C3F1. Groups of the three genotypes were maintained on either a basal diet or one containing 0.1% of the peroxisome-proliferating agent, nafenopin, for six weeks. In both control and nafenopin-exposed groups, the C57 strain displayed higher acyl-CoA oxidase activity levels than the C3H mice, whereas the activity levels of catalase and glutathione peroxidase were not different for the two inbred strains. The groups of similarly fed B6C3F1 hybrids had intermediate values for acyl-CoA oxidase. Several other parameters relating to peroxisome proliferation did not differ among the three genotypes. Acyl-CoA oxidase levels in cultured hepatocytes from C57 mice were greater than those in hepatocytes obtained from the C3H strain during two days in culture and this difference was maintained for 4 days by nafenopin exposure. Acyl-CoA oxidase is central to the hypothetical H2O2 mechanism of peroxisome proliferator-induced hepatocarcinogenesis and, therefore, the genetic difference documented here may lead to a useful approach in testing this hypothesis.

Acyl-CoA Oxidase↗