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Biomedical subjects

J Seal

Publications and source records attributed to J Seal.

17 recordsLinked to original sources
PubMed2006

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories.

Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of 12, is a rare and malignant form of the illness, which may have more salient genetic influence. Since the initial report of association between neuregulin 1 (NRG1) and schizophrenia in 2002, numerous independent replications have been reported. In the current study, we genotyped 56 markers (54 single-nucleotide polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS patients and their parents. We used family-based association analysis for both diagnostic (extended transmission disequilibrium test) and quantitative phenotypes (quantitative transmission disequilibrium test) and mixed-model regression. Most subjects had prospective anatomic brain magnetic resonance imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165 healthy controls in the MRI study to examine genetic risk effects on normal brain development. Individual markers showed overtransmission of alleles to affecteds (P=0.009-0.05). Further, several novel four-marker haplotypes demonstrated significant transmission distortion. There was no evidence of epistasis with SNPs in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid social functioning. Further, possession of the risk allele was associated with different trajectories of change in lobar volumes. In the COS group, risk allele carriers had greater total gray and white matter volume in childhood and a steeper rate of subsequent decline in volume into adolescence. By contrast, in healthy children, possession of the risk allele was associated with different trajectories in gray matter only and was confined to frontotemporal regions, reflecting epistatic or other illness-specific effects mediating NRG1 influence on brain development in COS. This replication further documents the role of NRG1 in the abnormal brain development in schizophrenia. This is the first demonstration of a disease-specific pattern of gene action in schizophrenia.

Adolescent↗
PubMed2000

How can autologous blood transfusions help our patients?

In modern day clinical nursing practice, respecting and encouraging patient autonomy, together with acting as advocate for the patient, is an integral part of holistic patient care. We have a 'duty of care' to our patients. So why, in the early days of the 21st century, are we still transfusing our patients with homologous blood products when there is a safer alternative which has been recognised for almost 200 years?

Blood Transfusion, Autologous↗
PubMed1999

Reorganization of area 5 neuron activity in trained deafferented monkeys.

A command function is attributable to certain area 5 neurons which clearly fire before movement in trained monkey. Statistical analysis allowed us to define two categories of spontaneous firing mode for these cells: type I which exhibits a random pattern of discharge (14%), and type II displaying markedly "bursty firing". After deafferentation, both categories were still observed in the same proportion. However, the discharge pattern and frequency in type II cells remained altered for 5 months. This paralleled rises in neural latency response (RS) and reaction time (RT). Beginning the 6th month, there was a progressive reorganization of the spontaneous activity along with normalization of RS and RT. Our results support the idea that an enhancement of the excitability of these area 5 neurons, initially depressed by the suppression of sensory inputs, occurs over time. This sensitivity gain could be due to neural network rearrangements induced by repetitive operant solicitation.

Afferent Pathways↗
PubMed1997

Why does the single neuron activity change from trial to trial during sensory-motor task?

Single neuron activities from cortical areas of a monkey were recorded while performing a sensory-motor task (a choice reaction time task). Quantitative trial-by-trial analysis revealed that the timing of peak activity exhibited large variation from trial to trial, compared to the variation in the behavioral reaction time of the task. Therefore, we developed a multi-unit dynamic neural network model to investigate the effects of structure of neural connections on the variation of the timing of peak activity. Computer simulation of the model showed that, even though the units are connected in a cascade fashion, a wide variation exists in the timing of peak activity of neurons because of parallel organization of neural network within each unit.

Animals↗
PubMed1993

Intensity to force translation: a new effect of stimulus-response compatibility revealed by analysis of response time and electromyographic activity of a prime mover.

In reaction time studies of stimulus-response compatibility, emphasis has been placed on the influence of spatial stimulus-response relationships, but what seems to be essential for the emergence of an effect of stimulus-response compatibility is the existence of a conceptual match between stimulus and response variables. This notion was at the origin of the present study to assess the compatibility relationship between the intensity of a visual stimulus and the force of a voluntary muscle contraction. A stimulus-response compatibility effect was demonstrated. This effect was entirely due to premotoric processes.

Adult↗
PubMed1989

Sensory and motor functions of the superior parietal cortex of the monkey as revealed by single-neuron recordings.

From the literature on the functional role of the superior parietal cortex, it can be seen that this cortical area has been attributed both sensory and motor functions, as demonstrated by anatomical and lesion studies. Single-unit recordings in behaving monkeys have equally been interpreted as demonstrating these two functions. However, the results of recent experiments using this technique suggest that area 5 may function in the transformation of sensory activity into motor activity.

Animals↗
PubMed1988

Neuronal activity and information processing in motor control: from stages to continuous flow.

Some years ago, we proposed, along with others, that the isomorphism between models of information processing by stages and the organization of neural pathways connecting functionally specialized neuronal networks was a guideline for conducting experiments in which the integration of methods and concepts of cognitive psychology and of neurophysiology was a promising approach to increase our knowledge of the processes responsible for motor control. At a time when models of serially organized information processing stages are being increasingly challenged, the deciphering of the underlying brain processes increasingly suggests that current views about the linkage between neural structures and behavioural functions must be reconsidered. First, at the "molar" level, the notion of a functional specialization of neuronal networks as, for example, being "sensory", "sensorimotor" or "motor", has to be viewed as a quantitative and not as a qualitative concept. Second, at the "molecular" level, the notion of a clear-cut functional differentiation between neuronal units, or between small sets of neurons, must similarly be revised: a neuron may be more or less "sensory" or "motor" and, moreover, may share both these functional properties to varying degrees. When the brain processes responsible for movement control are reconsidered in the light of these two concepts--that is a functional heterogeneity of structurally defined neuronal networks, as well as a continuum in functional specification of isolated neuronal units--data collected by using single-cell recording of neuronal activity fit well into the model of a continuous flow of information processing: neural pathways from the cortical parietal association areas to the corticospinal apparatus appear as a privileged sensorimotor information stream along which the amount of neuronal activity responsible for movement planning progressively decreases, while the amount of neuronal activity involved in movement execution progressively increases.

Animals↗
PubMed1986

The formulae-relating slopes, correlation coefficients and variance ratios used to determine stimulus- or movement-related neuronal activity.

When recording single neuron discharge in an animal during the performance of a conditioned task, the functional interpretation of any change in neuronal activity after the conditioned stimulus but before the conditioned task is difficult. So far, such changes have been described as either stimulus- or movement-related. One way of classifying these two types of response has been to use the slope and correlation coefficient between the response latency and the behavioural reaction time. We show that this method is poor and propose a more valid approach.

Animals↗
PubMed1986

A program for analysing single neuron activity by methods based on estimation of a change-point.

A program for analysing the sequences of discharge of a single neuron is presented. This program performs the following tasks: it tests if there is a neuronal response after a stimulus, it estimates the response latency and, in the case of an experiment with a conditioned movement, it estimates the onset of the movement and gives indications about the functional role of the neuron by analysing the variances of the stimulus-response and response-movement times. The methods used have been developed by the authors and are based on the estimation of a change point. The basic methods are published elsewhere but some novelties are presented here, in particular a robust estimator of a variance ratio.

Action Potentials↗
PubMed1985

A quantitative analysis of stimulus- and movement-related responses in the posterior parietal cortex of the monkey.

The posterior parietal cortex (areas 5 and 7) in monkeys has been described as a higher association cortex and as such, area 5 has been attributed a complex somaesthetic function. More recently, a role in the formation of motor commands has been postulated for these two cortical areas. We have been particularly interested in the role area 5 neurons may have in movement initiation. Single neuron activity was recorded in area 5 during the performance of a trained forelimb movement in monkeys and neuronal responses which occurred prior to movement were observed. In the present report, we have examined the neuronal discharge data trial by trial using a technique of data analysis which enabled us to separate the changes in neuronal activity into stimulus- or movement-related responses. Both stimulus- and movement-related responses were identified. The stimulus-related responses were not simple sensory responses since they were also influenced by the timing of the onset of movement. These results suggest that certain area 5 neurons may be involved in the linking of sensory inputs with motor outputs. Cerebrocerebellar loops may be a pathway in this linkage. The latencies of the movement-related responses were such that corollary discharge from the motor cortex may have played a role in this activity. Such corollary discharge may be a form of information used by the animal to execute movement in the absence of peripheral feedback.

Afferent Pathways↗
PubMed1984

Activity of nigral dopaminergic neurons after lesion of the neostriatum in rats.

As shown by post-mortem analysis the major neuropathological trait of Huntington's chorea is a degeneration of the intrinsic neurons of the neostriatum (caudate nucleus and putamen). Such a situation can be reproduced by a destruction of the neostriatum by kainic acid. When injected into the caudate nucleus this excitatory amino acid destroys the intrinsic neurons of the neostriatum and spares fairly well the passing fibers. In the present work, we have chosen to examine the influence of neostriatal destruction on the activity of identified dopaminergic cells in the pars compacta of the substantia nigra. As a key element in the nigro-neostriato-nigral loop, this structure is a relevant site for observing the functional effects of neostriatal lesion. Our research hypothesis was based on the generally accepted view that the suppression of the important neostriato-nigral pathway and in particular the inhibitory GABAergic contingent, could generate a hyperactivity of nigral dopaminergic cells. One may therefore consider that the dopaminergic hyperactivity produces abnormal messages which can influence via several pathways the motoneurons, and which participates in the genesis of the hyperkinetic movements characteristic of chorea. After destruction of the neostriatum, we have shown that the pattern of discharge of most identified nigral dopaminergic neurons becomes greatly disorganized. This drastic change in the pattern of activity cannot be interpreted as the simple 'lift of a brake' on these cells by the suppression of the inhibitory GABAergic striato-nigral tract.

Animals↗
PubMed1983

A statistical method for the estimation of neuronal response latency and its functional interpretation.

The functional role of many central nervous structures has been inferred from the temporal relationship of a neuronal response with the different sensory and motor events in an experimental design such as when an animal performs a trained movement in response to a conditioned stimulus. However, this kind of data analysis leads to problems in estimating the occurrence and latency of any neuronal response. We examine these problems and propose a novel technique of data analysis to estimate the point of change in a sequence of neuronal discharge. Furthermore, data can be tested to see whether the neuronal response is related to the conditioned stimulus or the motor act. The method can also be used in the simple situation of determining the latency of a neuronal response after a stimulus.

Animals↗
PubMed1983

Instruction-related changes of neuronal activity in area 5 during a simple forearm movement in the monkey.

Unit recordings were made in area 5 of monkeys during the performance of a sound-triggered movement of the forearm. Changes in neuronal activity prior to the movement were observed in 188 neurons recorded in both normal and deafferented animals. When the discharge of these cells was analyzed as peristimulus histograms, it was seen that 152 neurons presented a pattern of discharge which was characterized by a brief modification in activity with a relatively constant latency after the auditory cue. Similar changes were observed in normal and deafferented animals but the latency was not the same for the two groups. These neurons may reflect the presence of a sensorimotor interface for the integration of instructions for movement and the subsequent genesis of motor commands.

Afferent Pathways↗
PubMed1982

Activity of neurons in area 5 during a simple arm movement in monkeys before and after deafferentation of the trained limb.

Unit recordings were performed in the postcentral cortex and focused on area 5 of awake monkeys during the execution of a learned movement of the contralateral forearm so that the time relationship between the motor act and any modification of neuronal activity could be precisely correlated. Recordings were obtained from intact animals (561 neurons) and after deafferentation (C1-T7) of the trained limb (344 neurons). Of the movement-related neurons in normal animals, 243 cells were located in area 5 and these cells were divided into two populations. The first population (66% of movement-related neurons) presented modifications of activity after the onset of movement and receptive fields, often complex, were identifiable for these somaesthetic-like cells. No such neurons were found in the same cortical area after deafferentation. The second population (34% of movement-related neurons) presented modifications of activity related to movement but these changes occurred well before the onset of movement, up to 280 ms before. These cells were also characterized by an absence of sensory modulation and they represented the entire population of movement-related neurons recorded in area 5 after deafferentation (124 neurons). The first population appears to subserve a complex somaesthetic function. The second population is subject to purely central influences which, in part, may be due to corollary discharge or internal feedback. However, this population most likely represents a command apparatus for movement located 'upstream' to the motor cortex.

Afferent Pathways↗
PubMedDate not supplied

The analysis of neuronal discharge sequences: change-point estimation and comparison of variances.

A key problem in neurophysiology is to determine whether, after presentation of a stimulus, there has been a modification in the discharge of a recorded neuron and if so, an attempt is made to estimate the latency of the response. The estimation problem can be considered as that of the estimation of a change-point in a sequence of random variables. The gamma distribution is adequate to model the distribution of intervals between action potentials for different types of neurons. Simulations show that the maximum likelihood estimator based on this model is efficient and robust. An additional problem, in the case of experiments in which a movement follows the stimulus, is to determine whether a response is related to the stimulus or to the movement. A test based on the comparison of marginal scales of a bivariate distribution is proposed. The whole procedure has been tested in simulation and with real examples.

Action Potentials↗
PubMedDate not supplied

The challenges of change for learning disabilities nurses.

In the past ten years there have been many changes in care provision for people with learning disabilities. This article outlines the changes and discusses the impact they have had on the learning disability nurse's role.

Clinical Competence↗