Biomedical subjects

A Simmons

Publications and source records attributed to A Simmons.

At least 55 records · Page 3Linked to original sources

PubMed2000

The functional neuroanatomy of implicit-motion perception or representational momentum.

BACKGROUND: When we view static scenes that imply motion - such as an object dropping off a shelf - recognition memory for the position of the object is extrapolated forward. It is as if the object in our mind's eye comes alive and continues on its course. This phenomenon is known as representational momentum and results in a distortion of recognition memory in the implied direction of motion. Representational momentum is modifiable; simply labelling a drawing of a pointed object as 'rocket' will facilitate the effect, whereas the label 'steeple' will impede it. We used functional magnetic resonance imaging (fMRI) to explore the neural substrate for representational momentum. RESULTS: Subjects participated in two experiments. In the first, they were presented with video excerpts of objects in motion (versus the same objects in a resting position). This identified brain areas responsible for motion perception. In the second experiment, they were presented with still photographs of the same target items, only some of which implied motion (representational momentum stimuli). When viewing still photographs of scenes implying motion, activity was revealed in secondary visual cortical regions that overlap with areas responsible for the perception of actual motion. Additional bilateral activity was revealed within a posterior satellite of V5 for the representational momentum stimuli. Activation was also engendered in the anterior cingulate cortex. CONCLUSIONS: Considering the implicit nature of representational momentum and its modifiability, the findings suggest that higher-order semantic information can act on secondary visual cortex to alter perception without explicit awareness.

Adult↗

PubMed2000

Cortical activity during rotational and linear transformations.

Neuroimaging studies of cortical activation during image transformation tasks have shown that mental rotation may rely on similar brain regions as those underlying visual perceptual mechanisms. The V5 complex, which is specialised for visual motion, is one region that has been implicated. We used functional magnetic resonance imaging (fMRI) to investigate rotational and linear transformation of stimuli. Areas of significant brain activation were identified for each of the primary mental transformation tasks in contrast to its own perceptual reference task which was cognitively matched in all respects except for the variable of interest. Analysis of group data for perception of rotational and linear motion showed activation in areas corresponding to V5 as defined in earlier studies. Both rotational and linear mental transformations activated Brodman Area (BA) 19 but did not activate V5. An area within the inferior temporal gyrus, representing an inferior satellite area of V5, was activated by both the rotational perception and rotational transformation tasks, but showed no activation in response to linear motion perception or transformation. The findings demonstrate the extent to which neural substrates for image transformation and perception overlap and are distinct as well as revealing functional specialisation within perception and transformation processing systems.

Adult↗

PubMed2000

Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI.

The aim of this study was to investigate whether previously observed hypofrontality in adolescents with attention deficit-hyperactivity disorder (ADHD) during executive functioning [Rubia K, Overmeyer S, Taylor E, Brammer M, Williams S, Simmons A, Andrew C, Bullmore ET. Hypofrontality in attention deficit hyperactivity disorder during higher order motor control: a study using fMRI. Am J Psychiatry 1999;156(6):891-896] could be attributed to delayed maturation of frontal cortex. Brain activation of 17 healthy subjects, 9 adolescents and 8 young adults, during performance of a motor response inhibition task and a motor timing task was measured using functional magnetic resonance imaging (fMRI). The effect of age on brain activation was estimated, using the analysis of variance and regression, at both voxel and regional levels. In the delay task, superior performance in adults was paralleled by a significantly increased power of response in a network comprising prefrontal and parietal cortical regions and putamen. In the stop task, alternative neuronal routes--left hemispheric prefrontal regions in adults and right hemispheric opercular frontal cortex and caudate in adolescents--seem to have been recruited by the two groups for achieving comparable performances. A significant age effect was found for the prefrontal activation in both task, confirming the hypothesis of a dysmaturational pathogenesis for the hypofrontality in ADHD.

Adolescent↗

PubMed2000

Quantitative perfusion imaging in carotid artery stenosis using dynamic susceptibility contrast-enhanced magnetic resonance imaging.

Quantitative, multislice dynamic susceptibility contrast-enhanced MRI perfusion measurements were used to determine the patterns of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and normalized first moment of the tissue deltaR2-time curve (N) in 11 subjects with carotid artery occlusion or stenosis. MTT correlated with degree of carotid stenosis, whereas a range of alterations in CBF and CBV were found presumably reflecting variables degrees of collateral flow. There was no significant correlation between MRI and SPET flow perfusion measurements, with increasing disparity between the two techniques at higher inter-hemispheric flow ratios. The effect of obtaining the arterial input function (AIF) from the middle cerebral artery (MCA) ipsilateral or contralateral to the stenosis was determined. Despite the use of an AIF from the MCA, which is distal to the circle of Willis, and hence the major sources of collateral supply, there was still some extra dispersion of the contrast agent bolus due to differences in arrival time.

Aged↗

PubMed2000

Towards a functional neuroanatomy of self processing: effects of faces and words.

We studied the neural correlates of self vs. non-self judgements using functional magnetic resonance imaging (fMRI). Individually tailored faces and personality trait words were used as stimuli in three experiments (exp.). In the first two experiments, brain activation was measured while subjects viewed morphed versions of either their own (self face exp.) or their partner's face (partner's face exp.), alternating in blocks with presentation of an unknown face. In the self face exp. right limbic areas (hippocampal formation, insula, anterior cingulate), the right middle temporal lobe, left inferior parietal and left prefrontal regions showed signal changes. In the partner's face exp., only the right insula was activated. In the third exp., subjects made decisions about psychological trait adjectives previously categorized as describing their own attributes. Activation was present in the precuneus, the left parietal lobe, left insula/inferior frontal gyrus and the left anterior cingulate. A reaction time advantage was present when subjects responded to self-relevant words. The main area with signal changes during self-reference processing, regardless of the type of stimulus, was the left fusiform gyrus. The self-relevant stimuli engaged to a differential extent long term and working memory, semantic and emotional processes. We suggest that regions activated by these stimuli are engaged in self-processing.

Adult↗

PubMed2000

Molecular localisation of a G-protein mRNA using differential display and in situ hybridization.

Defining molecular repertoires within virally infected tissues of the nervous system may provide insight into the pathogenesis of, and immunity to, neurotropic viruses. Here we report the application of such a method, namely mRNA differential display (DD), to the identification of mRNAs that are expressed at different levels in herpes simplex virus (HSV) infected nervous tissue from immunocompetent and CD8(+) lymphocyte depleted mice. Small amounts of input RNA can be used by DD, making the method ideal for experiments based on murine sensory ganglia (DRG), which on average yield less than 0.5 microg of total RNA. In the current work, DD facilitated the identification of a mRNA whose abundance in HSV-infected ganglia, based on Northern blot analysis, was reduced in mice depleted of CD8(+) cells. The cloned product of this mRNA was of particular interest to our research as sequence data strongly suggested that it represented the murine homologue of the alpha chain of a G protein termed Golf. This G protein had not previously been reported from dorsal root ganglial tissue. RT-PCR confirmed the presence of Golf in DRG and in situ hybridization studies localised this molecule to primary sensory neurons. These data indicate that DD is sufficiently robust to be applied to the study of virus pathogenesis within the nervous system.

Animals↗

PubMed2000

Corpus callosum may be similar in children with ADHD and siblings of children with ADHD.

No previous studies have used morphological neuroimaging to compare children with ADHD with siblings of children with ADHD. To test the hypothesis that the total size of the corpus callosum is altered in children with hyperkinetic disorder, the corpus callosum was outlined from a single midline protondensity weighted slice (containing the septum pellucidum). Fifteen boys with a refined phenotype of ADHD (mean age 10.2 years) and 15 healthy male siblings of children with ADHD (mean age 10.6 years) were enrolled in the study. The two groups were compared for global brain size and the callosal areas of Witelson. No significant differences were found between the study and comparison groups for any of the corpus callosum areas, even after age, global brain size, and handedness were covaried (using MANOVA). In addition, corpus callosum sizes do not seem to differ between children with ADHD and unaffected siblings of children with ADHD. Clinicians should not base their pathophysiological diagnosis of this disorder on an abnormality of callosal development.

Adolescent↗

PubMed2000

Imaging attentional and attributional bias: an fMRI approach to the paranoid delusion.

BACKGROUND: The pathophysiology of auditory hallucinations and delusions of control has been elucidated using functional imaging. Despite their clinical importance, there have been few similar attempts to investigate paranoid delusions. We have examined two components of social cognition (attentional and attributional biases) that contribute to the formation and maintenance of paranoid delusions, using functional magnetic resonance imaging (fMRI). METHOD: Normal subjects performed tasks requiring attentional and attributional judgements. We investigated the neural response particularly associated with attention to threatening material relevant to self and with the 'self-serving' attributional bias. RESULTS: The determination of relevance to self of verbal statements of differing emotional valence involved left ventrolateral prefrontal cortex (left inferior frontal gyrus, BA 47), right caudate and right cingulate gyrus (BA 24). Attention to threatening material relevant to self differentially activated a more dorsal region of the left inferior frontal gyrus (BA 44). Internal attributions of events, where the self was viewed as an active intentional agent, involved left precentral gyrus (BA 6) and left middle temporal gyrus (BA 39). Attribution of events in a non 'self-serving' manner required activation of the left precentral gyrus (BA 6). CONCLUSIONS: Anomalous activity or connectivity within these defined regions may account for the attentional or attributional biases subserving paranoid delusion formation. This provides a simple model for paranoid delusion formation that can be tested in patients.

Adult↗

PubMed2000

Quantitative proton magnetic resonance spectroscopy of the subcortical white matter in motor neuron disease.

BACKGROUND: Using proton magnetic resonance spectroscopy, the authors have previously demonstrated a reduction in the N-acetyl aspartate/(creatine and phosphocreatine) (NAA/(Cr + PCr)) ratio in the motor region in bulbar-onset MND patients, attributed to neuronal loss or dysfunction leading to a reduction in NAA. We have expanded this analysis to evaluate absolute concentrations of NAA, (Cr + PCr) and choline-containing compounds (Cho) in the subcortical white matter in the motor region in 16 MND patients (8 with bulbar onset and 8 with limb onset) and 8 healthy, age-matched controls. METHODS: Single voxel 1H-MRS was performed using a PRESS localization sequence. Metabolite concentrations were determined using the water signal as an internal standard. RESULTS: We found no differences in the concentrations of NAA ([NAA]), (Cr + PCr) ([Cr + PCr]) or Cho ([Cho]) in the motor region on comparing the total MND group and controls (P > 0.3). No difference was found in [NAA] in the bulbar-onset group compared with the limb-onset group (P = 0.70), but [Cr + PCr] was significantly higher in the bulbar-onset group (P = 0.04). CONCLUSIONS: Our results suggest that [Cr + PCr] may be affected by the pathological process in MND, and this should be considered in the interpretation of metabolite peak area ratios. The elevated (Cr + PCr) may represent gliosis in the subcortical white matter in the motor cortex region.

Adult↗

PubMed2000

Cluster analysis of diffusion tensor magnetic resonance images in human head injury.

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.

Adolescent↗

PubMed2000

Granzyme A, a noncytolytic component of CD8(+) cell granules, restricts the spread of herpes simplex virus in the peripheral nervous systems of experimentally infected mice.

Control of ganglionic herpes simplex virus (HSV) infection depends on CD8(+) cells but not on the death of infected neurons. Primarily, perforin and granzyme B mediate CD8(+) cell cytotoxicity, whereas the in vivo functions of granzyme A, a third granule protein, are unknown. Here, it is shown that granzyme A restricts the interneuronal spread of HSV and significantly influences ganglionic virus load.

Animals↗

PubMed2000

Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations.

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.

Adult↗

PubMed2000

Exploring the social brain in schizophrenia: left prefrontal underactivation during mental state attribution.

OBJECTIVE: Evidence suggests that patients with schizophrenia have a deficit in "theory of mind," i.e., interpretation of the mental state of others. The authors used functional magnetic resonance imaging (MRI) to investigate the hypothesis that patients with schizophrenia have a dysfunction in brain regions responsible for mental state attribution. METHOD: Mean brain activation in five male patients with schizophrenia was compared to that in seven comparison subjects during performance of a task involving attribution of mental state. RESULTS: During performance of the mental state attribution task, the patients made more errors and showed less blood-oxygen-level-dependent signal in the left inferior frontal gyrus. CONCLUSIONS: To the authors' knowledge, this is the first functional MRI study to show a deficit in the left prefrontal cortex in schizophrenia during a socioemotional task.

Adult↗

PubMed2000

Sources of error in comparing functional magnetic resonance imaging and invasive electrophysiological recordings.

OBJECT: Several authors have recently reported studies in which they aim to validate functional magnetic resonance (fMR) imaging against the accepted gold standard of invasive electrophysiological monitoring. The authors have conducted a similar study, and in this paper they identify and quantify two characteristics of these data that can make such a comparison problematic. METHODS: Eight patients in whom surgery for epilepsy was performed and five healthy volunteers underwent fMR imaging to localize the part of the sensorimotor cortex responsible for hand movement. In the patient group subdural electrode mats were subsequently implanted to identify eloquent regions of the brain and the epileptogenic zone. The fMR imaging data were processed to correct for motion during the study and then registered with a postimplantation computerized tomography (CT) scan on which the electrodes were visible. The motion during imaging in the two groups studied, and the deformation of the brain between the preoperative images and postoperative scans were measured. The patients who underwent epilepsy surgery moved significantly more during fMR imaging experiments than healthy volunteers performing the same motor task. This motion had a particularly increased out-of-plane component and was significantly more correlated with the stimulus than in the volunteers. This motion was especially increased when the patients were performing a task on the side affected by the lesion. The additional motion is hard to correct and substantially degrades the quality of the resulting fMR images, making it a much less reliable technique for use in these patients than in others. Also, the authors found that after electrode implantation, the brain surface can shift more than 10 mm relative to the skull compared with its preoperative location, substantially degrading the accuracy of the comparison of electrophysiological measurements made in the deformed brain and fMR studies obtained preoperatively. CONCLUSIONS: These two findings indicate that studies of this sort are currently of limited use for validating fMR imaging and should be interpreted with care. Additional image analysis research is necessary to solve the problems caused by patients' motion and brain deformation.

Cerebral Cortex↗

PubMed2000

Effects of three different doses of a bolus injection of gadodiamide: assessment of regional cerebral blood volume maps in a blinded reader study.

BACKGROUND AND PURPOSE: Reconstruction of first-pass bolus information to derive regional cerebral blood volume (rCBV) maps is commonly performed in many centers; however, various protocols with different doses of paramagnetic contrast injections have been reported. We evaluated the dose dependency of rCBV maps in a brain tumor population by using three different doses of gadodiamide injection to evaluate their diagnostic accuracy in blinded reader sessions. METHODS: Eighty-three patients with intraaxial brain tumors (72 gliomas) were studied at three centers and randomized to receive a bolus injection of 0.1, 0.2, or 0.3 mmol/kg per body weight of gadodiamide. rCBV maps were generated from T2*-weighted gradient-echo echoplanar sequences at 1.5 T. Data processing was performed according to the indicator dilution theory. RESULTS: The mean contrast-to-noise ratio (CNR) was significantly different between gadodiamide doses of 0.1 and 0.2 mmol/kg (CNR = 8.7 and 15.7) and between 0.1 and 0.3 mmol/kg (CNR = 17.7). No significant difference was found between doses of 0.2 and 0.3 mmol/kg. Sensitivity for the differentiation of benign and malignant brain tumors was 80%, 95%, and 91%, and specificity was 45%, 54%, and 43% by blinded readings at 0.1, 0.2, and 0.3 mmol/ kg, respectively, as compared with histologic findings. Nonblinded readings had a sensitivity of 83%, 100%, and 90% and a specificity of 82%, 100%, and 73% at 0.1, 0.2, and 0.3 mmol/kg, respectively. CONCLUSION: A dose of 0.2 mmol/kg of gadodiamide is recommended for reconstruction of rCBV maps if data are acquired with the T2*-weighted protocol described.

Blood Volume↗

PubMed1999

Physical map and characterization of transcripts in the candidate interval for familial chondrocalcinosis at chromosome 5p15.1.

The gene for familial chondrocalcinosis (MIM 118600; gene symbol CCAL2) has been localized to a 0.8-cM interval on the short arm of chromosome 5, between the polymorphic microsatellite markers D5S416 and D5S2114. We have undertaken the physical and transcript mapping of this interval, as well as regions telomeric to the interval, in an attempt to define ultimately the gene for this disorder. The physical map is composed of YAC, BAC, PAC, and cosmid resources and spans a physical distance of approximately 0.3 Mb. Using cDNA selection, we have identified eight novel transcripts in and around the interval; two of the selected transcripts reside in the candidate interval. We have also more precisely placed several expressed sequence tags (ESTs) that were previously mapped by radiation hybrid analysis and were reported to reside in or near the candidate interval. Two of the ESTs analyzed overlap with the selected cDNAs that reside in the candidate interval. All of the selected cDNAs are expressed partial transcripts, as determined by Northern blot analysis, and using RT-PCR analysis, we have determined that the cDNAs that reside in the candidate interval are expressed in cartilage and synovium, tissues that are presumably relevant to the chondrocalcinosis phenotype.

Adult↗

PubMed1999

Diffusion tensor MRI assesses corticospinal tract damage in ALS.

BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI. OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI. METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS-11 with limb onset (mean age 54.5 +/- 10.7 years) and 11 with bulbar onset (mean age 49.6 +/- 11.7 years)-and compared them with 20 healthy, age-matched controls (mean age 46.0 +/- 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated. RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration. CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.

Adult↗

PubMed1999

Golfalpha is expressed in primary sensory neurons outside of the olfactory neuroepithelium.

Golfalpha is the alpha chain of a trimolecular stimulatory G protein originally described as the G protein responsible for signal transduction in odourant recognition within neurons of the olfactory neuroepithelium. While applying the technique of mRNA differential display to herpes simplex virus infected tissue, a partial cDNA clone corresponding to the mouse homologue of Golfalpha was isolated from sensory dorsal root ganglia. Levels of this transcript were reduced following viral infection and this reduction was enhanced in CD8(+) depleted mice. The presence of this G protein within sensory ganglia was confirmed with Northern blotting and PCR and in situ hybridization studies localised Golfalpha expression exclusively to neurons within this tissue.

Animals↗