Biomedical subjects

A Simmons

Publications and source records attributed to A Simmons.

At least 73 records · Page 4Linked to original sources

PubMed1999

Attenuated frontal activation in schizophrenia may be task dependent.

UNLABELLED: Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.

Adult↗

PubMed1999

The functional anatomy of the McCollough contingent colour after-effect.

We report two functional magnetic resonance imaging (fMRI) experiments which reveal a cortical network activated when perceiving coloured grids, and experiencing the McCollough effect (ME). Our results show that perception of red-black and green-black grids activate the right fusiform gyrus (area V4) plus the left and right lingual gyri, right striate cortex (V1) and left insula. The ME activated the left anterior fusiform gyrus as well as the ventrolateral prefrontal cortex, and in common with colour perception, the left insula. These data confirm the critical role of the fusiform gyrus in actual and illusory colour perception as well as revealing localized frontal cortical activation associated with the ME, which would suggest that a 'top-down' mechanism is implicated in this illusion.

Adult↗

PubMed1999

Quality control for functional magnetic resonance imaging using automated data analysis and Shewhart charting.

A data acquisition and analysis protocol for quality control (QC) of functional magnetic resonance imaging studies is presented. Two sets of data are acquired, single-timepoint data for measurement of signal-to-ghost and signal-to-noise ratios, and multiple-timepoint data for measurement of short-term drift. Since manual data analysis can be time consuming and an impediment to regular QC, an automated data processing scheme is presented. The use of automated Shewhart charting is proposed to identify significant changes in each parameter over the long term. The protocol has successfully identified system faults and deteriorations undetected by conventional QC.

Artifacts↗

PubMed1999

Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI.

A technique for assessing in vivo fiber connectivity in the human brain is presented. The method utilizes a novel connectivity algorithm that operates in three spatial dimensions and uses estimates of fiber tract orientation and tissue anisotropy, obtained from diffusion tensor magnetic resonance imaging, to establish the pathways of fiber tracts. Sample in vivo connectivity images from healthy human brain are presented that demonstrate connections in the white matter tracts. White matter connectivity information is potentially of interest in the study of a range of neurological, psychiatric, and developmental disorders and shows promise for following the natural history of disease.

Algorithms↗

PubMed1999

Anti-CD8 treatment alters interleukin-4 but not interferon-gamma mRNA levels in murine sensory ganglia during herpes simplex virus infection. Brief report.

Clearance of herpes simplex virus (HSV) from sensory ganglia of infected mice is dependent on CD8(+) cells but not on the death of infected neurons. The mechanism of action of CD8(+) cells in HSV infected ganglia is therefore unknown. The determine which cytokines might be involved in the CD8(+) cell dependent response to ganglionic HSV infection, IL-2, IL-4, IL-6, IL-10, and IFN-gamma mRNA levels were measured in infected ganglia from immunocompetent and anti-CD8 treated mice. Anti-CD8 treatment increased the abundance of mRNA encoding IL-4, and, to a lesser extent, IL-2, and IL-6. Significantly, IFN-gamma mRNA was not affected.

Animals↗

PubMed1999

Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil.

Functional magnetic resonance imaging (fMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome, using a multiplexed visual and auditory stimulation paradigm. In both normal and narcoleptic subjects, mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P = 0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant. The alerting action, and imaging response, to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects, but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil. However, in the modafinil-treated group of 8 normal and 8 narcoleptic subjects, there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation (visual, P = 0.002; and auditory, P = 0.001). No correlation was observed in placebo-treated subjects (P = 0.99 and 0.77, respectively). Although limited by the small number of subjects, and the lack of an objective measure of alertness, the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance imaging may be a valuable addition to established studies of attention.

Acoustic Stimulation↗

PubMed1999

Social intelligence in the normal and autistic brain: an fMRI study.

There is increasing support for the existence of 'social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers et al. 1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the 'social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J. Neuropath. Exp. Neurol., 47, 369]. We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of autism.

Adult↗

PubMed1999

Distinct hyperintense MRI signal changes in the corticospinal tracts of a patient with motor neuron disease.

Neuroimaging in motor neuron disease (MND) is currently performed to exclude other pathologies, though abnormalities may be seen which are consistent with the diagnosis. We report a patient with rapidly progressive MND exhibiting extensive changes on a variety of contemporary magnetic resonance images, which is most likely to represent severe corticospinal tract degeneration.

Amyotrophic Lateral Sclerosis↗

PubMed1999

Remission of inflammatory arthropathy in association with anti-CD20 therapy for non-Hodgkin's lymphoma.

We describe a case involving a 53-yr-old male with a marginal zone B-cell lymphoma, associated with an IgM paraprotein and a rheumatoid factor-negative inflammatory polyarthropathy, treated with monoclonal anti-CD20 antibody. During the subsequent 12 weeks, evidence of synovitis reduced to a negligible level, despite no significant change in lymphoma bulk or paraprotein level. The relationship between the lymphoma and the arthropathy, and the likely mechanism of remission of the arthropathy, are discussed in the context of the potential value of anti-CD20 therapy in rheumatoid arthritis.

Antibodies, Monoclonal↗

PubMed1999

Herpes simplex virus genome isomerization: origins of adjacent long segments in concatemeric viral DNA.

Herpes simplex virus type 1 DNA isomerization was studied by using a viral mutant, 5B8, lacking the unique SpeI site of its parent, SC16. In coinfected cells, SC16 genomic long segments flanked 5B8 genomes in all possible orientations with similar frequencies. Thus, recombination between progeny of different replication templates is sufficient to explain genomic isomerization.

Animals↗

PubMed1999

Cell surface expression of H2 antigens on primary sensory neurons in response to acute but not latent herpes simplex virus infection in vivo.

CD8(+) T lymphocytes and class I major histocompatibility complex (MHC-I) molecules profoundly influence the severity of neuronal herpes simplex virus (HSV) infection in experimentally infected mice. Paradoxically, neurons are classically regarded as MHC-I deficient. However, it is shown here that H2-encoded heavy chains (alphaCs) and their associated light chain, beta2 microglobulin, are present on the surfaces of primary sensory neurons recovered from sensory ganglia within 1 to 2 weeks of HSV infection. During this time, some neurons are found to be tightly associated with T cells in vivo. Prior data showed that termination of productive HSV infection in the peripheral nervous system is not dependent on cell-mediated lysis of infected neurons. Consistent with these data, immunogold electron microscopy showed that the density of cell surface H2 on neurons is an order of magnitude lower than on satellite glia, which is predicted to favor a noncytolytic CD8 cell response.

Animals↗

PubMed1999

Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI.

BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

Adult↗

PubMed1999

Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI.

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that attention deficit hyperactivity disorder (ADHD) is associated with a dysfunction of prefrontal brain regions during motor response inhibition and motor timing. METHOD: Generic brain activation of seven adolescent boys with ADHD was compared to that of nine comparison subjects equivalent in sex, age, and IQ while they were performing a stop task, requiring inhibition of a planned motor response, and a motor timing task, requiring timing of a motor response to a sensory cue. RESULTS: The hyperactive adolescents showed lower power of response in the right mesial prefrontal cortex during both tasks and in the right inferior prefrontal cortex and left caudate during the stop task. CONCLUSIONS: ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.

Adolescent↗

PubMed1999

Restricted replication of herpes simplex virus in satellite glial cell cultures clonally derived from adult mice.

To determine the possible influence of satellite glial cells on restricting the spread of herpes simplex virus in the peripheral nervous system, HSV replication was studied in clonally derived cultures of satellite glial cells from adult animals. Satellite cells were purified by exploiting their close anatomical association with primary sensory neurons. Dissociated neurons from dorsal root ganglia were micro-manipulated to remove all but one of the attached satellite cells and cultured in the presence of the mitogenic stimulators bovine pituitary extract and cholera toxin. Following a lag phase of 20-30 days some of the individual satellite cells began to proliferate. Initial cultures demonstrated bipolar morphology similar to cultured Schwann cells, some of which differentiated into large astrocytic whorl-like cells on subsequent passage. Immunocytochemical and molecular studies demonstrated that these cells, designated Sat.1, express glial fibrillary acidic protein, confirming their glial origin and by electron microscopy they were shown to be phagocytic. Under single step viral growth conditions Sat.1 cells were restrictive for HSV replication, producing in the order of 1000 times less infectious virus than Vero cells, a standard permissive cell line. These results suggest that satellite cells, which tightly encase sensory neurons, play a role in restricting interneural spread of HSV within the peripheral nervous system.

Animals↗

PubMed1999

Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging.

The optimization of acquisition parameters for precise measurement of diffusion in anisotropic systems is described. First, an algorithm is presented that minimizes the bias inherent in making measurements with a fixed set of gradient vector directions by spreading out measurements in 3-dimensional gradient vector space. Next, it is shown how the set of b-matrices and echo time can be optimized for estimating the diffusion tensor and its scalar invariants. The standard deviation in the estimate of the tensor trace in a water phantom was reduced by more than 40% and the artefactual anisotropy was reduced by more than 60% when using the optimized scheme compared with a more conventional scheme for the same scan time, and marked improvements are demonstrated in the human brain with the optimized sequences. Use of these optimal schemes results in reduced scan times, increased precision, or improved resolution in diffusion tensor images. Magn Reson Med 42:515-525, 1999.

Adult↗

PubMed1998

Investigation of facial recognition memory and happy and sad facial expression perception: an fMRI study.

We investigated facial recognition memory (for previously unfamiliar faces) and facial expression perception with functional magnetic resonance imaging (fMRI). Eight healthy, right-handed volunteers participated. For the facial recognition task, subjects made a decision as to the familiarity of each of 50 faces (25 previously viewed; 25 novel). We detected signal increase in the right middle temporal gyrus and left prefrontal cortex during presentation of familiar faces, and in several brain regions, including bilateral posterior cingulate gyri, bilateral insulae and right middle occipital cortex during presentation of unfamiliar faces. Standard facial expressions of emotion were used as stimuli in two further tasks of facial expression perception. In the first task, subjects were presented with alternating happy and neutral faces; in the second task, subjects were presented with alternating sad and neutral faces. During presentation of happy facial expressions, we detected a signal increase predominantly in the left anterior cingulate gyrus, bilateral posterior cingulate gyri, medial frontal cortex and right supramarginal gyrus, brain regions previously implicated in visuospatial and emotion processing tasks. No brain regions showed increased signal intensity during presentation of sad facial expressions. These results provide evidence for a distinction between the neural correlates of facial recognition memory and perception of facial expression but, whilst highlighting the role of limbic structures in perception of happy facial expressions, do not allow the mapping of a distinct neural substrate for perception of sad facial expressions.

Adult↗

PubMed1998

The functional anatomy of imagining and perceiving colour.

We report two functional magnetic resonance imaging experiments which reveal similarities and differences between perceptual and imaginal networks within the single visual submodality of colour. The first experiment contrasted viewing of a coloured and grey-scale Mondrian display, while the second contrasted a relative colour judgement with a spatial task and required the generation of mental images. Our results show that colour perception activates the posterior fusiform gyrus bilaterally (area V4), plus right-sided anterior fusiform and lingual gyri, striate cortex (area V1), and the left and right insula. Colour imagery activated right anterior fusiform gyrus, left insula, right hippocampus and parahippocampal gyrus, but not V4 or V1. The findings reconcile neurological case studies suggesting a double dissociation between deficits in colour imagery and perception and point to anterior fusiform, parahippocampal gyri and hippocampus as the location for stored representations of coloured objects.

Brain Mapping↗

PubMed1998

Prefrontal cortex involvement in selective letter generation: a functional magnetic resonance imaging study.

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Adult↗