PubMed Health⌕ Search

Biomedical subjects

Andrew Simmons

Publications and source records attributed to Andrew Simmons.

27 records · Page 2Linked to original sources
PubMed2003

Cognitive effects of nicotine in humans: an fMRI study.

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

Adult↗
PubMed2002

Neural correlates of British sign language comprehension: spatial processing demands of topographic language.

In all signed languages used by deaf people, signs are executed in "sign space" in front of the body. Some signed sentences use this space to map detailed "real-world" spatial relationships directly. Such sentences can be considered to exploit sign space "topographically." Using functional magnetic resonance imaging, we explored the extent to which increasing the topographic processing demands of signed sentences was reflected in the differential recruitment of brain regions in deaf and hearing native signers of the British Sign Language. When BSL signers performed a sentence anomaly judgement task, the occipito-temporal junction was activated bilaterally to a greater extent for topographic than nontopographic processing. The differential role of movement in the processing of the two sentence types may account for this finding. In addition, enhanced activation was observed in the left inferior and superior parietal lobules during processing of topographic BSL sentences. We argue that the left parietal lobe is specifically involved in processing the precise configuration and location of hands in space to represent objects, agents, and actions. Importantly, no differences in these regions were observed when hearing people heard and saw English translations of these sentences. Despite the high degree of similarity in the neural systems underlying signed and spoken languages, exploring the linguistic features which are unique to each of these broadens our understanding of the systems involved in language comprehension.

Adolescent↗
PubMed2002

Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation.

Procedural learning (PL) is a type of rule-based learning in which performance facilitation occurs with practice on task without the need for conscious awareness. Schizophrenic patients have often (though not invariably) been found to show impaired PL. We performed functional magnetic resonance imaging (fMRI) during a blocked, periodic sequence-learning task with groups of: (i) healthy subjects, and (ii) schizophrenic patients on conventional antipsychotics. Healthy subjects showed significant PL, but patients did not. In healthy subjects, PL was associated with increased activation in the striatum, thalamus, cerebellum, precuneus, medial frontal lobe, and cingulate gyrus. The power of activation in the thalamus, striatum, precuneus, cingulate gyrus and BA 6 was related to the magnitude of PL in these subjects. No regions, except the anterior inferior gyrus, were significantly activated in patients. The caudate nucleus, thalamus, precuneus, and sensorimotor regions were activated significantly differently between the two groups. The findings demonstrate the involvement of the striatum, cerebellum, thalamus, cingulate gyrus, precuneus, and sensorimotor regions in PL. Further fMRI studies of PL in normal subjects treated with conventional antipsychotics, drug naïve patients, and patients given atypical antipsychotics would help to clarify the roles of schizophrenic disease processes and antipsychotic medication in impaired PL and associated brain abnormalities in schizophrenia.

Adult↗
PubMed2002

Asperger syndrome: a proton magnetic resonance spectroscopy study of brain.

BACKGROUND: Asperger syndrome (AS; an autistic disorder) is associated with impaired social skills and obsessional/repetitive behavior. Patients with autism have significant abnormalities in the frontal lobe and frontoparietal connectivity. Nobody has examined the relationship between abnormalities in the frontal and parietal lobes and clinical symptoms in people with AS. METHODS: We used in vivo proton magnetic resonance spectroscopy to examine neuronal integrity of the medial prefrontal and parietal lobes in 14 non-learning-disabled adults with AS and 18 control subjects (of similar sex, age, and IQ). We obtained measures of the prefrontal lobe in 11, the parietal lobe in 13, and both lobes in 10 subjects with AS. We measured concentrations and ratios of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho). Levels of NAA, Cr + PCr, and Cho are indicators of neuronal density and mitochondrial metabolism, phosphate metabolism, and membrane turnover. Frontal metabolite levels were correlated with scores on the Yale-Brown Obsessive Compulsive Scale and the Autism Diagnostic Interview. RESULTS: Subjects with AS had a significantly higher prefrontal lobe concentration of NAA (z = -3.1; P =.002), Cr + PCr (z = -2.2; P =.03), and Cho (z = -2.9; P =.003). Increased prefrontal NAA concentration was significantly correlated with obsessional behavior (tau = 0.67; P =.005); increased prefrontal concentration of Cho, with social function (tau = 0.72; P =.02). We found no significant differences in parietal lobe metabolite concentrations. CONCLUSION: Subjects with AS have abnormalities in neuronal integrity of the prefrontal lobe, which is related to severity of clinical symptoms.

Adult↗
PubMed2002

Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time.

Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole-brain coverage with isotropic (2.5 x 2.5 x 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum-intensity projection algorithm. Finally, reconstruction of fiber-tract trajectories i.e., "tractography" was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 x 2.5 x 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols.

Adult↗
PubMed2002

Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759.

Keratolytic winter erythema is an autosomal dominant skin disorder characterised by erythema, hyperkeratosis, and peeling of the skin of the palms and soles, especially during winter. The keratolytic winter erythema locus has been mapped to human chromosome 8p22-p23. This chromosomal region has also been associated with frequent loss of heterozygosity in different types of cancer. To identify positional candidate genes for keratolytic winter erythema, a BAC contig located between the markers at D8S550 and D8S1695 was constructed and sequenced. It could be extended to D8S1759 by a partially sequenced BAC clone identified by database searches. In the 634 404 bp contig 13 new polymorphic microsatellite loci and 46 single nucleotide and insertion/deletion polymorphisms were identified. Twelve transcripts were identified between D8S550 and D8S1759 by exon trapping, cDNA selection, and sequence analyses. They were localised on the genomic sequence, their exon/intron structure was determined, and their expression analysed by RT-PCR. Only one of the transcripts corresponds to a known gene, encoding B-lymphocyte specific tyrosine kinase, BLK. A putative novel myotubularin-related protein gene (MTMR8), a potential human homologue of the mouse acyl-malonyl condensing enzyme gene (Amac1), and two transcripts showing similarities to the mouse L-threonine 3-dehydrogenase gene and the human SEC oncogene, respectively, were identified. The remaining seven transcripts did not show similarities to known genes. There were no potentially pathogenic mutations identified in any of these transcripts in keratolytic winter erythema patients.

Chromosomes, Artificial, Bacterial↗
PubMed2002

Brain anatomy and sensorimotor gating in Asperger's syndrome.

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

Adolescent↗
PubMed2002

A computational morphometric MRI study of schizophrenia: effects of hallucinations.

Quantitative magnetic resonance imaging (MRI) studies in patients with schizophrenia have shown reliable deficits in global tissue volume as well as some regionally specific changes, particularly in the temporal and frontal lobes. Recent technical advances have enabled automated voxel-wise analyses, which have the advantage of facilitating whole brain coverage without the restrictions of anatomically defined regions of interest and imperfect rater reliability. We used such a method to estimate voxel composition from segmentation of bivariate, dual-echo spin-echo data in 72 men with schizophrenia. Of these, 41 had a prominent history of auditory-verbal hallucinations and 31 had no such history. The patients were compared with 32 age, gender, handedness and IQ matched healthy controls. The study revealed localized areas of reduced grey-matter tissue proportion aggregating around the medial temporal lobes, the insulae, orbito-frontal cortex including anterior cingulate, and the precuneus (and lingual) gyri, in the schizophrenia patients as a whole. There were also reductions in white-matter tissue proportion extending along much of the large anterior-posterior frontal tracts in the right hemisphere. Small regions of increased grey matter were also noted in the right inferior parietal lobe. A contrast between the hallucinator and non-hallucinator patient groups showed a single region of reduced grey-matter tissue proportion affecting the left insula and adjacent temporal lobe. These data confirm the utility of voxel-based morphometric methods in schizophrenia research and point towards disruption to a 'paralimbic' neural network, as underlying schizophrenic psychopathology in general, with abnormalities of the left insula specifically related to hallucinations.

Adult↗