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1.
Database (Oxford) ; 20202020 01 01.
Article in English | MEDLINE | ID: mdl-32507889

ABSTRACT

Modern biology produces data at a staggering rate. Yet, much of these biological data is still isolated in the text, figures, tables and supplementary materials of articles. As a result, biological information created at great expense is significantly underutilised. The protein motif biology field does not have sufficient resources to curate the corpus of motif-related literature and, to date, only a fraction of the available articles have been curated. In this study, we develop a set of tools and a web resource, 'articles.ELM', to rapidly identify the motif literature articles pertinent to a researcher's interest. At the core of the resource is a manually curated set of about 8000 motif-related articles. These articles are automatically annotated with a range of relevant biological data allowing in-depth search functionality. Machine-learning article classification is used to group articles based on their similarity to manually curated motif classes in the Eukaryotic Linear Motif resource. Articles can also be manually classified within the resource. The 'articles.ELM' resource permits the rapid and accurate discovery of relevant motif articles thereby improving the visibility of motif literature and simplifying the recovery of valuable biological insights sequestered within scientific articles. Consequently, this web resource removes a critical bottleneck in scientific productivity for the motif biology field. Database URL: http://slim.icr.ac.uk/articles/.


Subject(s)
Amino Acid Motifs , Data Mining/methods , Databases, Protein , Molecular Sequence Annotation , Molecular Sequence Annotation/classification , Molecular Sequence Annotation/methods , Publications/classification
2.
Environ Sci Process Impacts ; 22(1): 173-186, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31808488

ABSTRACT

Volatile and semi-volatile organic compounds (S/VOCs) are ubiquitous in the environment, come from a wide variety of anthropogenic and biogenic sources, and are important determinants of environmental and human health due to their impacts on air quality. They can be continuously measured by direct mass spectrometry techniques without chromatographic separation by membrane introduction mass spectrometry (MIMS) and proton-transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). We report the operation of these instruments in a moving vehicle, producing full scan mass spectral data to fingerprint ambient S/VOC mixtures with high temporal and spatial resolution. We describe two field campaigns in which chemometric techniques are applied to the full scan MIMS and PTR-ToF-MS data collected with a mobile mass spectrometry lab. Principal Component Analysis (PCA) has been successfully employed in a supervised analysis to discriminate VOC samples collected near known VOC sources including internal combustion engines, sawmill operations, composting facilities, and pulp mills. A Gaussian mixture model and a density-based spatial clustering of application with noise (DBSCAN) algorithm have been used to identify sample clusters within the full time series dataset collected and we present geospatial maps to visualize the distribution of VOC sources measured by PTR-ToF-MS.


Subject(s)
Air Pollutants , Volatile Organic Compounds , Air Pollutants/analysis , Environmental Monitoring , Humans , Mass Spectrometry , Principal Component Analysis , Protons , Volatile Organic Compounds/analysis
3.
Rapid Commun Mass Spectrom ; 32(4): 349-360, 2018 Feb 28.
Article in English | MEDLINE | ID: mdl-29277946

ABSTRACT

RATIONALE: Volatile and semi-volatile organic compounds (S/VOCs) are important atmospheric pollutants affecting both human and environmental health. They are directly measured as an unresolved mixture using membrane introduction mass spectrometry (MIMS). We apply chemometric techniques to discriminate, classify, and apportion air samples from a variety of sources. METHODS: Full scan mass spectra of lab-constructed air samples were obtained using a polydimethylsiloxane membrane interface and an electron ionization ion trap mass spectrometer. Normalized full scan spectra were analyzed using principal component analysis (PCA), cluster analysis, and k-nearest neighbours (kNN) for sample discrimination and classification. Multivariate curve resolution (MCR) was used to extract pure component contributions. Similar techniques were applied to VOC mixtures sampled from different woodsmoke emissions and from the headspace above aqueous hydrocarbon solutions. RESULTS: PCA successfully discriminated 32 constructed VOC mixtures from nearly 300 air samples, with cluster analysis showing similar results. Further, kNN classification (k = 1) correctly classified all but one test set sample, and MCR successfully identified the pure compounds used to construct the VOC mixtures. Real-world samples resulting from the combustion of different wood species and those associated with water contaminated with different commercial hydrocarbon products were similarly discriminated by PCA. CONCLUSIONS: Chemometric techniques have been evaluated using full scan MIMS spectra with a series of VOC mixtures of known composition containing known compounds, and successfully applied to samples with known sources, but unknown molecular composition. These techniques have application to source identification and apportionment in real-world environmental samples impacted by atmospheric pollutants.


Subject(s)
Air Pollutants/analysis , Environmental Monitoring/methods , Mass Spectrometry/methods , Hydrocarbons/analysis , Multivariate Analysis , Principal Component Analysis , Smoke/analysis , Volatile Organic Compounds/analysis
4.
SAR QSAR Environ Res ; 26(3): 181-204, 2015.
Article in English | MEDLINE | ID: mdl-25783869

ABSTRACT

Machine learning (ML) methods have been applied to the analysis of a range of biological systems. This paper reviews the application of these methods to the problem domain of skin permeability and addresses critically some of the key issues. Specifically, ML methods offer great potential in both predictive ability and their ability to provide mechanistic insight to, in this case, the phenomena of skin permeation. However, they are beset by perceptions of a lack of transparency and, often, once a ML or related method has been published there is little impetus from other researchers to adopt such methods. This is usually due to the lack of transparency in some methods and the lack of availability of specific coding for running advanced ML methods. This paper reviews critically the application of ML methods to percutaneous absorption and addresses the key issue of transparency by describing in detail - and providing the detailed coding for - the process of running a ML method (in this case, a Gaussian process regression method). Although this method is applied here to the field of percutaneous absorption, it may be applied more broadly to any biological system.


Subject(s)
Artificial Intelligence , Skin Absorption , Skin/metabolism , Animals , Humans , Models, Biological , Permeability , Quantitative Structure-Activity Relationship
5.
Bioinformatics ; 28(7): 976-82, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22328783

ABSTRACT

MOTIVATION: Eukaryotic proteins are highly modular, containing multiple interaction interfaces that mediate binding to a network of regulators and effectors. Recent advances in high-throughput proteomics have rapidly expanded the number of known protein-protein interactions (PPIs); however, the molecular basis for the majority of these interactions remains to be elucidated. There has been a growing appreciation of the importance of a subset of these PPIs, namely those mediated by short linear motifs (SLiMs), particularly the canonical and ubiquitous SH2, SH3 and PDZ domain-binding motifs. However, these motif classes represent only a small fraction of known SLiMs and outside these examples little effort has been made, either bioinformatically or experimentally, to discover the full complement of motif instances. RESULTS: In this article, interaction data are analysed to identify and characterize an important subset of PPIs, those involving SLiMs binding to globular domains. To do this, we introduce iELM, a method to identify interactions mediated by SLiMs and add molecular details of the interaction interfaces to both interacting proteins. The method identifies SLiM-mediated interfaces from PPI data by searching for known SLiM-domain pairs. This approach was applied to the human interactome to identify a set of high-confidence putative SLiM-mediated PPIs. AVAILABILITY: iELM is freely available at http://elmint.embl.de CONTACT: toby.gibson@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Computational Biology/methods , Databases, Protein , Protein Interaction Domains and Motifs , Proteins/chemistry , Humans , Markov Chains , Protein Binding , Proteins/metabolism , Software
6.
Eur J Pharm Sci ; 45(1-2): 116-27, 2012 Jan 23.
Article in English | MEDLINE | ID: mdl-22101136

ABSTRACT

Discriminant analysis (DA) has previously been shown to allow the proposal of simple guidelines for the classification of 73 chemical enhancers of percutaneous absorption. Pugh et al. employed DA to classify such enhancers into simple categories, based on the physicochemical properties of the enhancer molecules (Pugh et al., 2005). While this approach provided a reasonable accuracy of classification it was unable to provide a consistently reliable estimate of enhancement ratio (ER, defined as the amount of hydrocortisone transferred after 24h, relative to control). Machine Learning methods, including Gaussian process (GP) regression, have recently been employed in the prediction of percutaneous absorption of exogenous chemicals (Moss et al., 2009; Lam et al., 2010; Sun et al., 2011). They have shown that they provide more accurate predictions of these phenomena. In this study several Machine Learning methods, including the K-nearest-neighbour (KNN) regression, single layer networks, radial basis function networks and the SVM classifier were applied to an enhancer dataset reported previously. The SMOTE sampling method was used to oversample chemical compounds with ER>10 in each training set in order to improve estimation of GP and KNN. Results show that models using five physicochemical descriptors exhibit better performance than those with three features. The best classification result was obtained by using the SVM method without dealing with imbalanced data. Following over-sampling, GP gives the best result. It correctly assigned 8 of the 12 "good" (ER>10) enhancers and 56 of the 59 "poor" enhancers (ER<10). Overall success rates were similar. However, the pharmaceutical advantages of the Machine Learning methods are that they can provide more accurate classification of enhancer type with fewer false-positive results and that, unlike discriminant analysis, they are able to make predictions of enhancer ability.


Subject(s)
Adjuvants, Pharmaceutic/pharmacology , Artificial Intelligence , Discriminant Analysis , Hydrocortisone/pharmacokinetics , Models, Biological , Skin Absorption/drug effects , Adjuvants, Pharmaceutic/chemistry , Adjuvants, Pharmaceutic/classification , Administration, Cutaneous , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Chemical Phenomena , Hydrocortisone/administration & dosage , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Mice , Mice, Hairless , Molecular Weight , Skin/drug effects , Skin/metabolism , Solubility , Support Vector Machine
7.
J Chromatogr Sci ; 47(1): 57-66, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19161658

ABSTRACT

Membrane introduction mass spectrometry (MIMS) is emerging as an important technique for on-line, real-time environmental monitoring. Because MIMS interfaces are simple and robust, they are ideally suited for operation in MS instrumentation used for in-field applications. We report the use of an on-line permeation tube to continuously infuse an isotopically labeled internal standard for continuous quantitative determinations in atmospheric and aqueous samples without the need for off-line calibration. This approach also provides important information on the operational performance of the analytical system during multi-day deployments. We report measured signal stability during on-line deployments in air and water of 7% based on variation of the internal standard response and have used this technique to quantify BTEX (benzene, toluene, ethylbenzenes, and xylenes), pinenes, naphthalene and 2-methoxyphenol (guaiacol) in urban air plumes at parts-per-billion by volume levels. Presented are several recent applications of MIMS-MS-MS for on-line environmental monitoring in atmospheric and aqueous environmental samples demonstrating laboratory, remote and mobile deployments. We also present the use of a thermally assisted MIMS interface for the direct measurement of polyaromatic hydrocarbons, alkylphenols, and other SVOCs in the low ppb range in aqueous environmental samples and discuss improvements in both the sensitivity and response times for selected SVOCs. The work presented in this paper represents significant improvements in field deployable mass spectrometric techniques, which can be applied to direct on-site analytical measurements of VOC and SVOCs in environmental samples.


Subject(s)
Air Pollutants/analysis , Mass Spectrometry/instrumentation , Mass Spectrometry/methods , Water Pollutants, Chemical/analysis , Membranes, Artificial , Polycyclic Aromatic Hydrocarbons/analysis , Reference Standards , Sensitivity and Specificity , Temperature , Time Factors , Volatilization
8.
Spinal Cord ; 44(9): 560-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16568143

ABSTRACT

STUDY DESIGN: Prospective experimental. OBJECTIVES: The aim of this study was to develop a quantitative sensory test (QST) that could be used for assessing the level and the density (degree of impairment) of spinal cord injury (SCI) and for monitoring neurological changes in patients with SCI. SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust, UK. METHODS: Perceptual threshold to 3 Hz cutaneous electrical stimulation was measured in 30 control subjects and in 45 patients with SCI at American Spinal Injuries Association (ASIA) sensory key points for selected dermatomes between C3 and S2 bilaterally. Electrical perceptual threshold (EPT) was recorded as the lowest ascending stimulus intensity out of three tests at which the subject reported sensation. The level of SCI according to EPT results was established for right and left sides as the most caudal spinal segment at which patient's EPT was within the control range (mean +/- 2 standard deviation (SD)). The level of SCI, according to EPT, was then compared with clinical sensory level derived according to ASIA classification. RESULTS: In the control group, EPT depended on the dermatome tested and was lowest for T1 (1.01 +/- 0.23 mA, mean +/- SD) and highest for L5 (3.32 +/- 1.14 mA). There was strong correlation between corresponding right and left dermatomes and between repeated assessments. In the SCI group, the level of lesion according to EPT and clinical testing was the same in 43 of the 90 tests (48%). In 37 cases (41%), the EPT level was higher than the clinical level, and in 10 cases (11%), it was lower. Below the level of lesion in incomplete SCI and in the zone of partial preservation in complete SCI, the EPT values in most dermatomes were raised compared with the control group. CONCLUSIONS: EPT is a simple, reproducible QST that can assess both the level and the density of SCI. It seems to add sensitivity and resolution to the standard clinical testing and could be a useful adjunct in longitudinal monitoring of patients with SCI for research purposes during natural recovery and therapeutic interventions. SPONSORSHIP: International Spinal Research Trust (ISRT), UK, Grant CLI001.


Subject(s)
Electric Stimulation/methods , Electrodiagnosis/methods , Sensory Thresholds , Skin/physiopathology , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/physiopathology , Adult , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Skin/innervation , Statistics as Topic
9.
J Neurol Neurosurg Psychiatry ; 76(9): 1259-63, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16107363

ABSTRACT

OBJECTIVE: The clinical and functional assessment of back muscles in human spinal cord injury (SCI) has received little attention. The aim of this study was to develop a method to assess the level of a thoracic spinal cord lesion based on the reflex activation of back muscles. METHODS: In 11 control subjects and in 12 subjects with clinically complete thoracic SCI (T2-T12), either a spinous process or an erector spinae muscle was prodded to elicit short latency reflexes recorded electromyographically at the spinal level of stimulation. An electromagnetic servo, attached to a blunt probe, applied stimuli at a frequency of 1 Hz and amplitude of 3 mm. Two trials of 50 mechanical prods were conducted at each site. RESULTS: Reflexes were evoked in control subjects in 82% of trials when the spinous process was prodded, and in 80% of trials when the muscle was prodded. In contrast, reflexes in SCI subjects could be elicited in 90-100% of trials two segments either above or below the lesion. Reflex responses in control subjects had a mean (SEM) latency of 5.72 (0.53) ms when the spinous process was prodded, and 5.42 (0.42) ms when the muscle was prodded. In the SCI subjects, responses had slightly (but insignificantly) longer latencies both above and below the lesion to either stimulus. The amplitude of reflex responses, expressed as a percentage of the background EMG, was on average 2-3 times larger at the three vertebral levels spanning the lesion in SCI subjects than at sites above or below the lesion or at any level in control subjects. CONCLUSION: We propose that the size of these mechanically evoked reflexes may be useful in determining the level of thoracic SCI. Furthermore, the reflexes might provide a valuable tool with which to monitor recovery after an intervention to repair or improve function of a damaged spinal cord.


Subject(s)
Mechanoreceptors/physiology , Motor Neurons/physiology , Muscle, Skeletal/physiology , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Adult , Back/innervation , Back/physiology , Case-Control Studies , Electromyography , Female , Humans , Male , Middle Aged , Muscle, Skeletal/innervation , Reflex
10.
Physiol Behav ; 83(5): 723-8, 2005 Jan 17.
Article in English | MEDLINE | ID: mdl-15639157

ABSTRACT

Glucose- and caffeine-containing energy drinks are said to influence the cognitive and cellular function within the brain. In this study, we have used the size of motor-evoked potentials (MEPs) produced in response to transcranial magnetic stimulation (TMS) of the motor cortex as an index of corticospinal excitability after ingestion of Lucozade and control drinks of glucose-containing or caffeine-containing carbonated water or carbonated water alone. With local ethical approval and informed consent, 10 healthy volunteers took part; surface electromyographic (EMG) recordings were taken from the thenar muscles of the dominant hand. In each assessment, 15 TMS stimuli were delivered over the motor cortex at an intensity of 1.1 T. Six subjects ingested a 380-ml bottle of carbonated Lucozade drink containing 68 g of glucose and 46 mg caffeine. Four subjects took part in three control trials drinking: (A) carbonated water with caffeine, (B) carbonated water with glucose and (C) carbonated water alone. Assessments were made before and at 30-min intervals after each drink. Mean fasting blood glucose concentrations and mean areas of MEPs rose after the Lucozade, remaining elevated for 90 min. Similar rises in MEP areas were seen in trials after drinking carbonated water with caffeine or with glucose, but not after drinking carbonated water alone. No change was seen in the M-wave evoked by electrical stimulation of the ulnar nerve. We conclude that Lucozade can affect the size of MEPs to activation of the motor cortex with fixed-intensity TMS. The underlying mechanism is likely to relate to the combined effects of caffeine and glucose on the brain.


Subject(s)
Beverages , Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Cerebral Cortex/drug effects , Glucose/pharmacology , Spinal Cord/drug effects , Adult , Blood Glucose/metabolism , Cerebral Cortex/physiology , Electric Stimulation , Electromagnetic Fields , Electromyography , Evoked Potentials, Motor/drug effects , Female , Humans , Male , Middle Aged , Motor Cortex/drug effects , Motor Cortex/physiology , Ulnar Nerve/physiology
11.
Pulm Pharmacol Ther ; 17(6): 431-4, 2004.
Article in English | MEDLINE | ID: mdl-15564087

ABSTRACT

We review the evidence that activation of the cerebral cortex can lead to movements of the vocal folds and possibly to cough. Electrical stimulation of the motor cortex can cause movements of the vocal folds and vocalizatioin, but cough has not been reported. The motor pathways are via the nucleus ambiguous and possibly the nucleus retroambuigualis in the brainstem. In humans, activation of the cerebral cortex by transcranial magnetic stimulation can cause motor potentials in the intrinsic laryngeal muscles and corresponding surface potentials. The relationships between the cortical sensation related to cough, the voluntary control of cough and the involvement of reflex pathways remain to be clarified.


Subject(s)
Cerebral Cortex/physiology , Cough/physiopathology , Larynx/physiology , Action Potentials , Brain Stem/physiology , Humans , Motor Cortex/physiology , Reflex/physiology , Vocal Cords/physiology
12.
Spinal Cord ; 42(7): 417-9, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15111994

ABSTRACT

STUDY DESIGN: Preliminary longitudinal clinical trial. OBJECTIVES: To test the efficacy of repetitive transcranial magnetic stimulation (rTMS) in modulating corticospinal inhibition and improving recovery in stable incomplete spinal cord injury (iSCI). SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Bucks, UK and Division of Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital, London, UK. METHODS: Four stable iSCI patients were treated with rTMS over the occipital cortex (sham treatment) and then over the motor cortex (real treatment). Patients were assessed using electrophysiological, clinical and functional measures before treatment, during sham treatment, during the therapeutic treatment and during a 3-week follow-up period. RESULTS: Cortical inhibition was reduced during the treatment week. Perceptual threshold to electrical stimulation of the skin, ASIA clinical measures of motor and sensory function and time to complete a peg-board improved and remained improved into the follow-up period. CONCLUSION: In this preliminary trial, rTMS has been shown to alter cortical inhibition in iSCI and improve the clinical and functional outcome. SPONSORSHIP: This work was supported by the International Spinal Research Trust.


Subject(s)
Electric Stimulation Therapy , Magnetics , Neural Inhibition/physiology , Spinal Cord Injuries/rehabilitation , Adult , Electromyography , Female , Humans , Male , Middle Aged , Motor Activity/physiology , Pain Threshold/physiology , Treatment Outcome
13.
Eur J Appl Physiol ; 92(1-2): 211-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15045505

ABSTRACT

Magnetic stimulation of the motor cortex with electromyographic recordings from exercising muscles has shown corticospinal excitability to be depressed following exercise. We now investigate whether this depression spreads to non-exercising muscles and its influence on performance. Healthy volunteers made unilateral biceps curls to exhaustion and, in another later session, for 25% of the time to exhaustion. Bilateral motor-evoked potentials (MEPs) in biceps brachii and first dorsal interosseus muscles were measured at 2-min intervals before and after exercise. In another experiment, subjects performed exhaustive curls and, in addition to MEP areas, force production in biceps, hand-grip force, simple reaction times and movement times were measured bilaterally. MEPs were depressed after exhaustive exercise in the exercising biceps for over 60 min; depression was also observed 10-15 min after exercise in the non-exercising biceps but not in the first dorsal interosseus of either hand. The shorter exercise period produced depression of MEPs only in the exercising muscle. After exhaustive exercise maximum voluntary contraction fell in the exercising biceps and this correlated with MEP areas. No reduction in force was seen in the non-exercising biceps but hand-grip force fell slightly in both arms. There was no change in reaction times or movement times. Depression of MEPs can occur in non-exercising homonymous muscles but not in heteronymous muscles and only when exercise levels are high. There was no measurable functional deficit in the non-exercising limb, so we conclude that the reduced corticospinal excitability observed in this limb has little or no consequence on the performance parameters measured.


Subject(s)
Evoked Potentials, Motor/physiology , Exercise/physiology , Motor Cortex/physiology , Muscle Contraction/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Reaction Time/physiology , Adaptation, Physiological/physiology , Adolescent , Adult , Arm/physiology , Female , Humans , Male , Muscle, Skeletal/innervation , Neural Inhibition/physiology , Sensitivity and Specificity
14.
Spinal Cord ; 42(6): 325-37, 2004 Jun.
Article in English | MEDLINE | ID: mdl-14968107

ABSTRACT

Clinical practice and scientific research may soon lead to treatments designed to repair spinal cord injury. Repair is likely to be partial in the first trials, extending only one or two segments below the original injury. Furthermore, treatments that are becoming available are likely to be applied to the thoracic spinal cord to minimise loss of function resulting from damage to surviving connections. These provisos have prompted research into the improvement of clinical and physiological tests designed (1) to determine the level and density of a spinal cord injury, (2) to provide reliable monitoring of recovery over one or two spinal cord segments, and (3) to provide indices of function provided by thoracic spinal root innervation, presently largely ignored in assessment of spinal cord injury. This article reviews progress of the Clinical Initiative, sponsored by the International Spinal Research Trust, to advance the clinical and physiological tests of sensory, motor and autonomic function needed to achieve these aims.


Subject(s)
Recovery of Function/physiology , Spinal Cord Injuries/physiopathology , Animals , Electrophysiology , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Humans , Muscle, Skeletal/innervation
15.
Int J Clin Pract ; 57(9): 831-3, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14686575

ABSTRACT

A previous electrophysiological investigation of schizophrenia using transcranial magnetic stimulation has shown altered corticospinal inhibition in medicated patients compared with drug-naive patients. Based on this work, we have carried out the first serial electrophysiological case studies of the human corticospinal system in schizophrenia in which a typical antipsychotic was compared with an atypical antipsychotic. We used transcranial magnetic stimulation-based techniques to study the time course of drug action in two antipsychotic drug-naive patients with schizophrenia; one patient treated with a typical antipsychotic (haloperidol) and the other with an atypical antipsychotic (risperidone). The typical antipsychotic was associated with an increase in corticospinal excitability which we found to occur 4-5 weeks after beginning medication. In contrast, the atypical antipsychotic was associated with a decrease in corticospinal excitability, occurring 3-4 weeks after starting pharmacotherapy. We conclude that these opposite neurophysiological effects are related to the relative dopaminergic and serotonergic actions of the two classes of drug.


Subject(s)
Antipsychotic Agents/therapeutic use , Evoked Potentials, Motor/drug effects , Haloperidol/therapeutic use , Motor Cortex/drug effects , Risperidone/therapeutic use , Schizophrenia/drug therapy , Adult , Analysis of Variance , Electromagnetic Fields , Electromyography/methods , Humans , Male , Motor Cortex/physiology , Psychiatric Status Rating Scales , Schizophrenia/physiopathology
16.
Int J Clin Pract ; 57(4): 262-4, 2003 May.
Article in English | MEDLINE | ID: mdl-12800454

ABSTRACT

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability. Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured. The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.


Subject(s)
Evoked Potentials, Motor , Fatigue Syndrome, Chronic/physiopathology , Motor Activity/physiology , Reaction Time/physiology , Adult , Electromyography/methods , Female , Humans , Linear Models , Magnetics , Male , Middle Aged , Motor Cortex/physiopathology , Movement/physiology , Psychomotor Performance , Spinal Cord/physiopathology
17.
Acta Psychiatr Scand ; 106(3): 224-6, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12197861

ABSTRACT

OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices. METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence. RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS. CONCLUSION: Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.


Subject(s)
Choline/metabolism , Fatigue Syndrome, Chronic/metabolism , Occipital Lobe/metabolism , Adult , Creatine/metabolism , Female , Frontal Lobe/metabolism , Humans , Magnetic Resonance Spectroscopy , Male
18.
Exp Physiol ; 86(5): 547-50, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11571481

ABSTRACT

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated. Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs. Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.


Subject(s)
Evoked Potentials, Motor/physiology , Fatigue Syndrome, Chronic/physiopathology , Motor Cortex/physiology , Pyramidal Tracts/physiology , Adult , Electromyography , Fatigue Syndrome, Chronic/etiology , Fatigue Syndrome, Chronic/psychology , Female , Humans , Magnetics , Male , Middle Aged , Neural Inhibition , Pain/physiopathology , Reaction Time , Surveys and Questionnaires
19.
Exp Physiol ; 86(1): 127-30, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11434326

ABSTRACT

Neurological testing tools for measuring and monitoring somatosensory function lack resolution and are often dependent on the clinician testing. In this study we have measured perceptual threshold (PT) to electrical stimulation of the skin and compared it with two-point discriminative ability (TPDA) in 12 control subjects. Tests were made on both sides of the body at American Spinal Injury Association (ASIA) key points on seven spinal dermatomes (C3 (neck), C4 (shoulder), C5 (upper arm), C6 (thumb), T8 (abdomen), L3 (knee), L5 (foot)) and in the mandibular (chin) and maxillary (cheek) fields of the trigeminal (V) nerve. Electrical stimulation (0.5 ms pulse width; 3 Hz) was applied via a self-adhesive cathode and an anode strapped to the wrist or ankle. The stimulus intensity was adjusted and PT was recorded as the lowest current at which the subject reported sensation. Sites were tested in random order. Indices for both TPDA and PT differed according to the dermatome tested but there was no correlation between TPDA and PT for any dermatome. There was good correlation between results from equivalent dermatomes on left and right sides for both PT and TPDA. Women frequently had lower mean (+/- S.E.) PTs and better TPDA than men; differences were significant (P < 0.05) for PT on the knee (women, 1.31 +/- 0.15 mA; men, 2.05 +/- 0.26 mA) and the foot (women, 2.90 +/- 0.19 mA; men, 4.13 +/- 0.28 mA) and for TPDA on the thumb (women, 3.8 +/- 0.2 mm; men, 7.8 +/- 1.3 mm) and the knee (women, 17.8 +/- 1.6 mm; men, 27.1 +/- 4.0 mm). Four subjects repeated the experiment on another day and the results correlated well with the first test for PT (r2, 0.62) and TPDA (r2, 0.48). PT differs between dermatomes in a predictable way but does not relate to TPDA. PT is easy to measure and may be a useful assessment tool with which to monitor recovery or deterioration in neuropathies, neurotrauma or after surgery.


Subject(s)
Sensory Thresholds , Skin Physiological Phenomena , Adult , Discrimination, Psychological , Electric Stimulation , Female , Humans , Male , Middle Aged , Reference Values , Sensation/physiology
20.
Motor Control ; 5(3): 270-80, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11438765

ABSTRACT

We used transcranial magnetic stimulation (TMS) to study corticospinal excitability to erector spinae (ES) muscles during graded voluntary contractions in bilateral trunk extension (BTE) and forced expiratory breath holding (FEBH) in normal individuals. Motor evoked potentials (MEPs) could be produced in all subjects in the absence of voluntary activation. At maximum voluntary contraction, levels of surface electromyographic (EMG) activity were 4 times greater during BTE than FEBH. When EMG was normalized to maximum, MEP amplitudes increased in proportion to contraction in both tasks. MEPs in FEBH were compared with extrapolated values at similar EMG levels in BTE and were found to be larger. EMG and MEPs in left and right ES were symmetrical throughout the range of contractions in both tasks. ES muscles have a facilitation pattern similar to that previously shown in leg muscles, but subtle differences at low levels of EMG suggest that the facilitation is dependent on the task.


Subject(s)
Motor Cortex/physiology , Muscle, Skeletal/physiology , Spine/physiology , Electromyography/methods , Humans , Magnetics/therapeutic use , Muscle, Skeletal/innervation
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