Biomedical subjects

John Suckling

Publications and source records attributed to John Suckling.

16 recordsLinked to original sources

PubMed2003

Detection of structural differences between the brains of schizophrenic patients and controls.

This paper investigates the validity of the null hypothesis: there are no structural differences between the brains of schizophrenic and normal control subjects that manifest themselves in MRI-T(2) data and distinguish the two populations in a statistically significant way. The data used refer to 21 schizophrenic patients and 19 normal controls, matched for age, sex and social background. The methodology used is based on three-dimensional texture analysis, which is used to quantify anisotropy in the data at scales of the order of a few millimetres. These data reject the null hypothesis. In addition, this article attempts to identify the regions of the brain that are responsible for the morphological characteristics that distinguish the two populations. For this purpose, it utilises a second texture analysis method that, in spite of being a global method, allows one to trace back to the data the origin of the features that most distinctly distinguish the two populations. This method indicates that the features that distinguish the two populations with P values smaller than 10(-6) are located in the most inferior part of the brain and in particular in the tissue that makes up the sulci. It is stressed that in order to preserve the integrity of the data for texture calculations, no registration of anatomical structures is performed, and the most inferior part of the brain is identified as referring to those slices of the scans that visually correspond to slices 1-12 of the Talairach and Tournoux brain atlas.

Adult↗

PubMed2003

The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study.

Patients with schizophrenia and related psychoses have an excess of minor neurological abnormalities (neurological soft signs) of unclear neuropathological origin. These include poor motor coordination, sensory perceptual difficulties and difficulties in sequencing complex motor tasks. Neurological soft signs seem not to reflect primary tract or nuclear pathology. It still has to be established whether neurological soft signs result from specific or diffuse brain structural abnormalities. Studying their anatomical correlates can provide not only a better understanding of the aetiopathogenesis of soft signs, but also of the pathophysiology of schizophrenia. Surprisingly few studies have investigated the brain correlates of neurological soft signs. In the present study, we investigated the relationship between brain structure and neurological soft signs in an epidemiologically based sample of 77 first-episode psychosis patients. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and voxel-based methods of image analysis to investigate brain structure. Higher rates of soft neurological signs (both motor and sensory) were associated with a reduction of grey matter volume of subcortical structures (putamen, globus pallidus and thalamus). Signs of sensory integration deficits were additionally associated with volume reduction in the cerebral cortex, including the precentral, superior and middle temporal, and lingual gyri. Neurological soft signs and their associated brain changes were independent of antipsychotic exposure. We conclude that neurological soft signs are associated with regional grey matter volume changes and that they may represent a clinical sign of the perturbed cortical-subcortical connectivity that putatively underlies psychotic disorders.

Adolescent↗

PubMed2003

Searching for a structural endophenotype in psychosis using computational morphometry.

Structural cerebral abnormalities are frequently observed in schizophrenia. These abnormalities may indicate vulnerability for the disorder, as evidenced by reports of familial clustering of measures identified through region-of-interest analyses using manual outlining procedures. We used computational morphometry to detect structural differences within the entire brain to further examine possible structural endophenotypes. Magnetic resonance imaging scans were obtained in 31 psychotic patients, 32 non-psychotic first-degree relatives of psychotic patients and 27 healthy controls. The images were processed using an automated procedure, yielding global grey matter, white matter, CSF and total brain volume. The relative distribution of grey matter was compared between groups on a clustered-voxel basis. Global grey matter and total brain volume did not differ between the groups. White matter volume was significantly higher and CSF volume significantly lower in relatives compared to both cases and controls. The clustered-voxel based group comparison yielded evidence for significant grey matter deficits in fronto-thalamic-cerebellar regions, in psychotic patients, whereas the most prominent deficits in relatives involved the cerebellum. Patients with psychosis and first-degree healthy relatives of patients with psychosis show cerebellar abnormalities, which may constitute a marker of genetic transmission.

Adolescent↗

PubMed2003

fMRI study of recognition of facial expressions in high-functioning autistic patients.

Autistic disorder is associated with deficits in social function. The disorder may be related to dysfunction in the brain regions that are involved in the process of recognising facial expressions of other persons. Using fMRI, we investigated whether autistic patients with relatively high IQ would have different brain activation on the tasks of recognition of facial expressions (i.e. faces expressing disgust, fear, and happiness) compared with normal control subjects. In disgust and fear recognition tasks, there were different patterns of brain activation in the cortico-limbic neural circuits qbetween autistic and normal groups. Patients with autistic disorder may have difficulty in grasping facially expressed qemotions in others, and thereby cannot manipulate the interpersonally derived information.

Adolescent↗

PubMed2003

Neural response to pleasant stimuli in anhedonia: an fMRI study.

The aim of this study was to investigate the neural correlates of affect processing in depressed anhedonic patients and healthy controls. Whole brain functional magnetic resonance imaging scans were obtained from seven females with a diagnosis of chronic unipolar major depression and high levels of anhedonia, and seven healthy females, while they were presented with positive valence and neutral images. Patients, compared to controls, showed decreased activation in medial frontal cortex, and increased activation in inferior frontal cortex, anterior cingulate, thalamus, putamen and insula. Reduced activation in medial frontal cortex may underlie abnormal positive affect processing in patients. Increases in neural activation in putamen and thalamus, previously found in transient sadness, and anterior cingulate could point to an involvement of these structures in anhedonia.

Adult↗

PubMed2003

Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison.

BACKGROUND: Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis. METHODS: We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people. FINDINGS: In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum. INTERPRETATION: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.

Adult↗

PubMed2003

Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics.

Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.

Adrenergic Uptake Inhibitors↗

PubMed2003

Wavelets and statistical analysis of functional magnetic resonance images of the human brain.

Wavelets provide an orthonormal basis for multiresolution analysis and decorrelation or 'whitening' of nonstationary time series and spatial processes. Wavelets are particularly well suited to analysis of biological signals and images, such as human brain imaging data, which often have fractal or scale-invariant properties. We briefly define some key properties of the discrete wavelet transform (DWT) and review its applications to statistical analysis of functional magnetic resonance imaging (fMRI) data. We focus on time series resampling by 'wavestrapping' of wavelet coefficients, methods for efficient linear model estimation in the wavelet domain, and wavelet-based methods for multiple hypothesis testing, all of which are somewhat simplified by the decorrelating property of the DWT.

Brain↗

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

Increased duration of illness is associated with reduced volume in right medial temporal/anterior cingulate grey matter in patients with chronic schizophrenia.

It is unclear whether the neuroanatomical abnormalities associated with schizophrenia change over the course of the disorder. We addressed this issue by examining whether the magnitude of structural brain abnormalities in patients with chronic schizophrenia was related to their duration of illness. Thirty-nine subjects with schizophrenia (34 male, 5 female, range of illness duration 2-31 years) were scanned using magnetic resonance imaging. Images were segmented into grey and white matter, cerebrospinal fluid and dura/blood vessels using the Structural Magnetic Resonance Toolkit (SMaRT). Voxel-based analysis identified brain areas whose volume varied significantly with time since the first onset of psychosis. Right medial temporal, medial cerebellar and bilateral anterior cingulate grey matter volume, and white matter volume in the right posterior limb of the internal capsule, were all negatively correlated with illness duration (p < 0.002). Conversely, illness duration was positively correlated with the volume of the right globus pallidus (p < 0.002). These correlations were not a function of chronological age or age at illness onset. The inverse correlation between right frontal, temporal and cerebellar volumes and the time since the onset of schizophrenia could reflect progressive tissue loss following the first episode of the disorder.

Adult↗

PubMed2002

Tracking sodium channels in live cells: confocal imaging using fluorescently labeled toxins.

One particularly important class of ion channels in excitable cells are the voltage-dependent sodium channels (VDSC). Knowledge of the distribution of VDSC in living cells is important for studies of neuronal excitability, development, and plasticity. Here, we demonstrate a new method for visualizing the spatial distribution of VDSC in living cells. To illustrate the capabilities of the technique, the distribution of VDSC in GH3 cells was revealed with fluorescent derivatives of the alpha-type and beta-type scorpion toxins in conjunction with laser scanning confocal microscopy. Cells exhibited fluorescent hot spots on the surface of the membrane. This characteristic staining pattern was prevented by pre-incubation with unlabeled native toxins and blocked by membrane depolarization for alpha-type toxins. Labeling was not observed in cells lacking sodium channels (HEK 293) after incubation with fluorescent-labeled toxins. Image processing techniques were applied to identify the location of each cluster of labeled VDSC in these cells. The proposed method eliminates artefacts commonly introduced during sample preparation for immunostaining and should prove to be a valuable research tool for investigating VDSC distribution in living specimens.

Animals↗

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

Neural systems underlying British Sign Language and audio-visual English processing in native users.

In order to understand the evolution of human language, it is necessary to explore the neural systems that support language processing in its many forms. In particular, it is informative to separate those mechanisms that may have evolved for sensory processing (hearing) from those that have evolved to represent events and actions symbolically (language). To what extent are the brain systems that support language processing shaped by auditory experience and to what extent by exposure to language, which may not necessarily be acoustically structured? In this first neuroimaging study of the perception of British Sign Language (BSL), we explored these questions by measuring brain activation using functional MRI in nine hearing and nine congenitally deaf native users of BSL while they performed a BSL sentence-acceptability task. Eight hearing, non-signing subjects performed an analogous task that involved audio-visual English sentences. The data support the argument that there are both modality-independent and modality-dependent language localization patterns in native users. In relation to modality-independent patterns, regions activated by both BSL in deaf signers and by spoken English in hearing non-signers included inferior prefrontal regions bilaterally (including Broca's area) and superior temporal regions bilaterally (including Wernicke's area). Lateralization patterns were similar for the two languages. There was no evidence of enhanced right-hemisphere recruitment for BSL processing in comparison with audio-visual English. In relation to modality-specific patterns, audio-visual speech in hearing subjects generated greater activation in the primary and secondary auditory cortices than BSL in deaf signers, whereas BSL generated enhanced activation in the posterior occipito-temporal regions (V5), reflecting the greater movement component of BSL. The influence of hearing status on the recruitment of sign language processing systems was explored by comparing deaf and hearing adults who had BSL as their first language (native signers). Deaf native signers demonstrated greater activation in the left superior temporal gyrus in response to BSL than hearing native signers. This important finding suggests that left- temporal auditory regions may be privileged for processing heard speech even in hearing native signers. However, in the absence of auditory input this region can be recruited for visual processing.

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↗

PubMed2002

A functional magnetic resonance imaging study of overt letter verbal fluency using a clustered acquisition sequence: greater anterior cingulate activation with increased task demand.

Regional cerebral activation during a cognitive task can vary with task demand and task performance. In a functional magnetic resonance imaging study, we examined the effect of manipulating task demand on activation during verbal fluency by using "easy" and "hard" letters. A "clustered" image acquisition sequence allowed overt verbal responses to be made in the absence of scanner noise which facilitated "on-line" measurement of task performance. Eleven right-handed, healthy male volunteers participated. Twice as many errors were produced with hard as with easy letters (20.8 +/- 13.6 and 10.1 +/- 10.7% errors, respectively). For both conditions, the distribution of regional activation was comparable to that reported in studies of covert verbal fluency, but with greater engagement of subcortical areas. The hard condition was associated with greater dorsal anterior cingulate activation than the easy condition. This may reflect the greater demands of the former, particularly in terms of arousal responses with increased task difficulty and the monitoring of potential response errors.

Adult↗

PubMedDate not supplied

Nonreplication of the association between ab-ridge count and cerebral structural measures in schizophrenia.

The origins of cerebral abnormalities in psychotic patients remain unknown. Dermatoglyphics are suitable markers of prenatal injury due to their fetal ontogenesis and their susceptibility to some of the factors that also affect cerebral development. In a previous study, positive associations between brain volumetric measures and a dermatoglyphic marker, the ab-ridge count, were reported. The present study is an attempt to replicate that finding in an independent sample. Magnetic resonance imaging (MRI) scans and dermatoglyphic measures were available for 29 schizophrenia patients (Research Diagnostic Criteria [RDC] criteria) and 26 unrelated healthy controls. The images were processed using an automated procedure, yielding volumes of total grey matter, white matter, cerebrospinal fluid (CSF), and total brain volume. The ab-ridge count was not positively associated with brain volumes in either patients or controls. The present findings do not support the hypothesis that the changes in brain volume seen in patients with schizophrenia are of prenatal origin.

Adolescent↗