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Biomedical subjects

A Simmons

Publications and source records attributed to A Simmons.

At least 91 records · Page 5Linked to original sources
PubMed1998

Prefrontal involvement in "temporal bridging" and timing movement.

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.

Adult↗
PubMed1998

Serial precision of metabolite peak area ratios and water referenced metabolite peak areas in proton MR spectroscopy of the human brain.

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that "disappointing in vivo repeatability...is likely to limit" the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H2O = 0.5%, Cho/H2O = 1.2%, Cr + PCr/H2O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H2O = 1.5%, Cho/H2O = 2.4%, Cr + PCr/H2O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H2O = 1.4%, Cho/H2O = 4.9%, Cr + PCr/H2O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H2O = 2.5%, Cho/H2O = 6.4%, Cr + PCr/H2O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall's assertion regarding disappointing repeatability of in vivo MRS.

Adult↗
PubMed1998

Precipitous clearance of herpes simplex virus antigens from the peripheral nervous systems of experimentally infected C57BL/10 mice.

Clearance of herpes simplex virus (HSV) from spinal ganglia of experimentally infected mice is known to be dependent on CD8+ T-cells but not on destruction of infected neurons, consistent with a non-cytolytic Tc2 response in the peripheral nervous system. Here, we demonstrate the striking rapidity of such a response in C57BL/10 mice. The number of neurons containing viral DNA and viral antigens increased until 136 h after inoculation of virulent HSV type 1 (strain SC16) into flank skin. Subsequent disappearance of HSV DNA and antigens from infected ganglia was virtually complete only 8 h later. A consistent and unexpected observation was detection of viral antigens in sensory nerve axons for at least 8 h after their disappearance from neuronal somas, raising the intriguing possibility that virus or viral proteins may be transported distally after infection has been terminated.

Animals↗
PubMed1998

Application of the extremum stack to neurological MRI.

The extremum stack, as proposed by Koenderink, is a multiresolution image description and segmentation scheme which examines intensity extrema (minima and maxima) as they move and merge through a series of progressively isotropically diffused images known as scale space. Such a data-driven approach is attractive because it is claimed to be a generally applicable and natural method of image segmentation. The performance of the extremum stack is evaluated here using the case of neurological magnetic resonance imaging data as a specific example, and means of improving its performance proposed. It is confirmed experimentally that the extremum stack has the desirable property of being shift-, scale-, and rotation-invariant, and produces natural results for many compact regions of anatomy. It handles elongated objects poorly, however, and subsections of regions may merge prematurely before each region is represented as a single node. It is shown that this premature merging can often be avoided by the application of either a variable conductance-diffusing preprocessing step, or more effectively, the use of an adaptive variable conductance diffusion method within the extremum stack itself in place of the isotropic Gaussian diffusion proposed by Koenderink.

Brain↗
PubMed1998

Estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation.

BACKGROUND: Epidemiologically-based rheumatology healthcare needs assessment requires an understanding of the incidence and prevalence of musculoskeletal disorders in the community, of the reasons why people consult in primary care, and of the proportion of people who would benefit from referral to secondary care and paramedical services. This paper reports the first phase of such a needs assessment exercise. SPECIFIC OBJECTIVE: To estimate the relative frequency of musculoskeletal pain in different, and multiple, anatomical sites in the adult population. SETTING: Three general practices in the former Tameside and Glossop Health Authority, Greater Manchester, UK, a predominantly urban area. DESIGN: Population survey. METHODS: An age and sex stratified sample of 6000 adults from the three practices was mailed a questionnaire that sought data on demographic factors, musculoskeletal symptoms (pain in the past month lasting for more than a week), and physical disability (using the modified Health Assessment Questionnaire--mHAQ). The areas of pain covered were neck, back, shoulder, elbow, hand, hip, knee, and multiple joints. The Carstairs index was used as a measure of social deprivation of the postcode sector in which the person lived. RESULTS: The response rate after two reminders was 78.5%. Non-responders were more likely to live in areas of high social deprivation. People who lived in more deprived areas were also more likely to report musculoskeletal pain, especially backpain. After adjusting for social deprivation the rates of musculoskeletal pain did not differ between the practices and so their results were combined. After adjustment for social deprivation, the most common site of pain was back (23%; 95% CI 21, 25) followed by knee (19%; 95% CI 18, 21), and shoulder (16%; 95% CI 14, 17). The majority of subjects who reported pain had pain in more than one site. The prevalence of physical disability in the community rose with age. It was highest in those with multiple joint problems but was also high in those with isolated back or knee pain. CONCLUSION: Musculoskeletal pain is common in the community. People who live in socially deprived areas have more musculoskeletal symptoms. Estimates of the overall burden of musculoskeletal pain that combine the results of site specific surveys will be too high, those that do not adjust for socioeconomic factors will be too low.

Adolescent↗
PubMed1998

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Adolescent↗
PubMed1998

A proton magnetic resonance spectroscopic study in ALS: correlation with clinical findings.

OBJECTIVE: To evaluate neuronal dysfunction in the motor region subcortical white matter in ALS using volumetric localized proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen patients with E1 Escorial definite, probable, or possible ALS and eight healthy age-matched control subjects were studied. The ALS patients were divided into those with limb onset (n = 8) and those with bulbar onset (n = 8). Measurements of the metabolic ratios N-acetylaspartate (NAA)/creatine and phosphocreatine (Cr+PCr), NAA/choline (Cho), and Cho/(Cr+PCr) were correlated with clinical assessments. RESULTS: We found no differences in the metabolic peak area ratios in the motor region when comparing the total ALS group and the control subjects. However, correlations were found between the NAA/(Cr+PCr) ratio and the E1 Escorial category (p = 0.03), the ALS severity scale (p = 0.01), and the Medical Research Council score (p = 0.06). No correlations were found between the NAA/(Cr+PCr) ratio and the Ashworth Spasticity Scale, reflex score, or disease duration (p > 0.16). Bulbar-onset patients had a lower NAA/(Cr+PCr) ratio in the motor region compared with limb-onset patients (p = 0.03). CONCLUSION: In vivo 1H-MRS of the subcortical white matter in the motor region is unlikely to be sensitive enough to detect early disease changes in ALS because there is considerable overlap between the metabolic peak area ratios from patients with ALS and normal control subjects. However, changes in the NAA/(Cr+PCr) metabolic peak area ratios correlate with clinical measures of disease severity, and this measure may be useful in monitoring disease progression.

Adult↗
PubMed1998

Exploring the temporal nature of hemodynamic responses of cortical motor areas using functional MRI.

OBJECTIVE: To use functional MRI (fMRI) to study grouped patterns of cerebral activation and the course of hemodynamic responses during performance of two activation tasks (paradigms) using a hand-held joystick to perform movements in a repetitively fixed direction and movements in freely selected random directions. BACKGROUND: Evidence from lesion, electrophysiologic, and functional imaging studies implicates prefrontal and mesial frontal cortex in motor preparation and primary motor cortex in motor execution. fMRI can be used to study cerebral activation and has practical advantages over other methods of functional neuroimaging. METHODS: We acquired 100 multislice T2*-weighted data sets from five healthy volunteers during performance of each paradigm using conventional fMRI. For each paradigm, rest and movement epochs were alternated every 30 seconds. After coregistration and spatial normalization, we combined the data for group studies. We used statistical parametric mapping to compare the early (first 15 seconds) components of the movement epochs with rest as well as the late (last 15 seconds) components of the movement epochs with rest. RESULTS: During the early phase of both paradigms, significant activation was present in rostral and caudal mesial premotor cortex. Right prefrontal cortex was significantly activated during the early component of freely selected joystick movements. Activation of rostral supplementary motor area was maintained during the late component of freely selected movements but decreased during repetitively fixed movements. In contrast, significant activation in contralateral sensorimotor cortex was maintained during both early and late components of both paradigms. CONCLUSIONS: fMRI can detect cortical activation. The temporal resolution of fMRI also allows adaptation of blood oxygenation level-dependent (BOLD) contrast signal to be detected in association cortex. However, the level of BOLD contrast signal in primary motor cortex remained significantly elevated throughout task performance.

Adult↗
PubMed1998

A simple method for investigating the effects of non-uniformity of radiofrequency transmission and radiofrequency reception in MRI.

Inhomogeneity of the transmitted or received B1 field leads to intensity variations in MR images and spatial dependence in apparent concentration in MR spectra. We describe a simple method for investigating such variations. The transmitted B1 field can be measured both in vivo and in vitro which allows investigation of sample dependent effects that can not be measured on phantoms. For homogeneous regions the method also allows the received B1 field to be measured both in vivo and in vitro. Our method uses only a standard spin echo pulse sequence and simple region of interest analysis and should be implementable on any commercial scanner. The method is demonstrated using a variety of transmission and reception radiofrequency coils both in vivo and in vitro.

Head↗
PubMed1998

Residual processing of chromatic signals in the absence of a geniculostriate projection.

We have investigated the residual processing of chromatic signals in a subject with unilateral damage to the primary visual cortex using psychophysical, pupillometric and functional magnetic resonance imaging (fMRI) methods. Of particular interest was to establish the correlation between the subject's ability to make use of chromatic signals in the blind hemifield to discriminate between different coloured targets, the corresponding residual pupil colour responses and the level and location of cortical activation generated by the same stimuli as revealed by fMRI. The results obtained using the three different experimental approaches are consistent and suggest that retrograde degeneration of thalamic and retinal chromatic processing mechanisms caused by damage to the primary visual cortex in man does not abolish completely the ability to process chromatic signals particularly when large, long-wavelength stimuli are employed.

Journal Article↗
PubMed1998

Residual processing of chromatic signals in the absence of a geniculostriate projection.

We have investigated the residual processing of chromatic signals in a subject with unilateral damage to the primary visual cortex using psychophysical, pupillometric and functional magnetic resonance imaging (fMRI) methods. Of particular interest was to establish the correlation between the subject's ability to make use of chromatic signals in the blind hemifield to discriminate between different coloured targets, the corresponding residual pupil colour responses and the level and location of cortical activation generated by the same stimuli as revealed by fMRI. The results obtained using the three different experimental approaches are consistent and suggest that retrograde degeneration of thalamic and retinal chromatic processing mechanisms caused by damage to the primary visual cortex in man does not abolish completely the ability to process chromatic signals particularly when large, long-wavelength stimuli are employed.

Color Perception↗
PubMed1997

In vivo proton magnetic resonance spectroscopy in polymyositis and dermatomyositis: a preliminary study.

The aim of the study is to determine whether biochemical abnormalities, such as lipid, creatine and choline metabolites, are observed in the more distal muscles of polymyositis (PM) and dermatomyositis (DM) patients. 12 patients suffering from chronic active PM/DM and 9 controls underwent a combined proton magnetic resonance (MR) imaging and proton MR spectroscopy study of the calf muscle. From a combination of T1-weighted MR images and corresponding fat suppressed images, fat infiltration into the muscle of both PM and DM patients was consistently observed. Muscular atrophy with a variable distribution was also noted in all patients. The biochemical profile of the localised proton MR spectra of soleus muscle showed reduction of both 'choline' to lipid and 'creatine' to lipid ratios in chronic PM and DM patients when compared with controls.

Adipose Tissue↗
PubMed1997

Pattern of neuronal activity associated with conscious and unconscious processing of visual signals.

Following striate cortex damage in monkeys and humans there can be residual function mediated by parallel visual pathways. In humans this can sometimes be associated with a "feeling" that something has happened, especially with rapid movement or abrupt onset. For less transient events, discriminative performance may still be well above chance even when the subject reports no conscious awareness of the stimulus. In a previous study we examined parameters that yield good residual visual performance in the "blind" hemifield of a subject with unilateral damage to the primary visual cortex. With appropriate parameters we demonstrated good discriminative performance, both with and without conscious awareness of a visual event. These observations raise the possibility of imaging the brain activity generated in the "aware" and the "unaware" modes, with matched levels of discrimination performance, and hence of revealing patterns of brain activation associated with visual awareness. The intact hemifield also allows a comparison with normal vision. Here we report the results of a functional magnetic resonance imaging study on the same subject carried out under aware and unaware stimulus conditions. The results point to a shift in the pattern of activity from neocortex in the aware mode, to subcortical structures in the unaware mode. In the aware mode prestriate and dorsolateral prefrontal cortices (area 46) are active. In the unaware mode the superior colliculus is active, together with medial and orbital prefrontal cortical sites.

Brain↗
PubMed1997

A functional magnetic resonance imaging study of episodic memory.

We have used whole brain fMRI and canonical variate analysis to investigate the anatomical location of brain activity subserving episodic memory encoding and recognition. Recognition of previously presented words did not specifically activate right prefrontal areas although right-sided activations were seen during transitions between the target and reference phases of the paradigm. Encoding was associated with left sided prefrontal activation, but this was within Broca's area rather than dorsolateral prefrontal cortex. The temporal resolution of fMRI, combined with analysis of the apparent functional connectivity of activations observed, revealed activity within complex networks each functionally specialized for the demands of particular aspects of a cognitive task.

Adult↗
PubMed1997

Concatemeric intermediates of equine herpesvirus type 1 DNA replication contain frequent inversions of adjacent long segments of the viral genome.

In common with other alpha-herpesviruses, the genome of equine herpesvirus type-1 (EHV-1) comprises covalently linked long and short unique sequences of DNA, each flanked by inverted repeats. Equimolar amounts of two genomic isomers, generated by free inversion of the short segment, relative to the long segment, are packaged into EHV-1 virions. In contrast with herpes simplex virus (HSV), inversion of genomic long segments has not been described. In the current work, the structures of high molecular weight intermediates of EHV-1 DNA replication were studied by field inversion gel electrophoresis. It is shown that adjacent long segments of the viral genome are frequently inverted in concatemeric intermediates of EHV-1 DNA replication. Further, like HSV concatemers, high molecular weight intermediates of EHV-1 replication are flanked exclusively by the long segment of the viral genome. Hence, despite the fact that only two, rather than four, isomers of EHV-1 DNA are packaged into virions, the intermediates of EHV-1 DNA replication closely resemble those of herpes simplex virus type 1 in structure. These data have implications relating to the mechanisms involved in packaging of alpha-herpesvirus DNA.

Animals↗
PubMed1997

The effects of standardization and reference values on patient classification for spine and femur dual-energy X-ray absorptiometry.

The effect of two methods for standardizing dual-energy X-ray absorptiometry (DXA) measurements on patient classification by the T-score has been determined for a group of over 2000 patients. The methods proposed by the International DXA Standardization Committee and the European Community's COMAC-BME group were used in conjunction with young reference data from the major DXA manufacturers, the COMAC-BME group and the third US National Health and Nutrition Examination Survey (NHANES III). The two standardization techniques produced dissimilar classifications as measured by the kappa statistic (kappa = 0.34-0.90), especially for the femoral neck, with up to 24.3% of patients reclassified from osteopenic to normal and 18.6% reclassified from osteoporotic to osteopenic when the standardization method was changed. Considering the effects of both reference data and standardization techniques together, there was a wide variation of patient classification, with the number of patients classified as osteoporotic varying from 9.6% to 21.1% for the postero-anterior spine L2-4 region and from 2.3% to 27.6% for the femoral neck. The agreement between different classifications ranged widely, from very poor to excellent (kappa = 0.02-0.98). The creation of standardized reference data must be an important priority in order to harmonize patient management using standardized BMD measurements. The choice of standardization technique, however, must be addressed in light of the results presented here.

Absorptiometry, Photon↗