Biomedical subjects

Steven C R Williams

Publications and source records attributed to Steven C R Williams.

At least 37 records · Page 2Linked to original sources

PubMed2004

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study.

BACKGROUND: Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. OBJECTIVES: To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. DESIGN: Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. SETTING: Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. PATIENTS AND OTHER PARTICIPANTS: We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers. Intervention After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. MAIN OUTCOME MEASURES: Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group x time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. RESULTS: Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. CONCLUSIONS: Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the dynamic range of the left prefrontal cortex. Changes in anterior cingulate function associated with symptomatic improvement indicate that fMRI may be a useful surrogate marker of antidepressant treatment response.

Affect↗

PubMed2004

Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.

Preferential migration of stem cells toward the site of a lesion is a highly desirable property of stem cells that allows flexibility in the site of graft implantation in the damaged brain. In rats with unilateral stroke damage, neural stem cells transplanted into the contralateral hemisphere migrate across to the lesioned hemisphere and populate the area around the ischaemic infarct. To date, the migration of neural stem cells in the damaged brain has been mainly inferred from snapshot histological images. In this study, we demonstrate that by pre-labelling neural stem cells with the bimodal contrast agent Gadolinium-RhodamIne Dextran [GRID, detectable by both magnetic resonance imaging (MRI) and fluorescent microscopy], the transhemispheric migration of transplanted neural stem cells contralateral to a stroke lesion can be followed in vivo by serial MRI and corroborated by subsequent histological analyses. Our results indicate that neural stem cells migrated from the injection tract mainly along the corpus callosum within 7 days of transplantation and extensively re-populated the peri-lesion area by 14 days following implantation. In contrast, neural stem cells transplanted into sham controls did not show any substantial migration outside of the injection tract, suggesting that the transcallosal migration observed in the stroke-lesioned animals is due to neural stem cells being attracted by the lesion site. In vivo tracking of the migration of neural stem cells responding to damage will greatly enhance our understanding of optimal transplantation strategies as well as how neural stem cells promote functional and anatomical recovery in neurological disorders.

Animals↗

PubMed2004

Differential neural responses to overt and covert presentations of facial expressions of fear and disgust.

There is debate in cognitive neuroscience whether conscious versus unconscious processing represents a categorical or a quantitative distinction. The purpose of the study was to explore this matter using functional magnetic resonance imaging (fMRI). We first established objective thresholds of the critical temporal parameters for overt and covert presentations of fear and disgust. Next we applied these stimulus parameters in an fMRI experiment to determine whether non-consciously perceived (covert) facial expressions of fear and disgust show the same double dissociation (amygdala response to fear, insula to disgust) observed with consciously perceived (overt) stimuli. A backward masking paradigm was used. In the psychophysics experiment, the following parameters were established: 30-ms target duration for the covert condition, and 170-ms target duration for the overt condition. Results of the block-design fMRI study indicated substantial differences underlying the perception of fearful and disgusted facial expressions, with significant effects of both emotion and target duration. Findings for the overt condition (170 ms) confirm previous evidence of amygdala activation to fearful faces, and insula activation to disgusted faces, and a double dissociation between these two emotions. In the covert condition (30 ms), the amygdala was not activated to fear, nor was the insula activated to disgust. Overall, findings demonstrate significant differences between the neural responses to fear and to disgust, and between the covert presentations of these two emotions. These results therefore suggest distinct neural correlates of conscious and unconscious emotion perception.

Adult↗

PubMed2004

Mapping IQ and gray matter density in healthy young people.

Magnetic resonance imaging (MRI) studies suggest that significant changes in gray matter density occur during adolescence because of brain maturation. It has also been reported that gray matter volume correlates with measures of intellectual ability. This study examined whether the relationship between general intellectual ability (IQ) and gray matter morphometry reflects differential involvement of particular cytoarchitectonic areas. We found positive correlations between IQ and gray matter density in the orbitofrontal cortex, cingulate gyrus, the cerebellum, and thalamus and negative correlations in the caudate nucleus. These findings suggest that general intellectual ability in healthy young people is related to specific brain regions known to be involved in the executive control of attention, working memory, and response selection.

Adolescent↗

PubMed2004

Medial prefrontal cortex activity associated with symptom provocation in eating disorders.

OBJECTIVE: The authors sought to identify neural correlates of eating disorders in order to contribute to the debate on the genesis and classification of eating disorders and provide endophenotypes for genetic research. METHOD: Twenty-six female patients with eating disorders (10 with bulimia nervosa, 16 with anorexia nervosa) and 19 healthy female comparison subjects matched for age and education were presented with food and aversive emotional images while brain activity was recorded with functional magnetic resonance imaging. RESULTS: Women with eating disorders identified the food stimuli as threatening and disgusting. In response to these stimuli, the women with eating disorders had greater activation in the left medial orbitofrontal and anterior cingulate cortices and less activation in the lateral prefrontal cortex, inferior parietal lobule, and cerebellum, relative to the comparison group. In addition, women with bulimia nervosa had less activation in the lateral and apical prefrontal cortex, relative to the comparison group. Between-group differences in response to nonspecific emotional stimuli were found in the occipital cortex, parietal cortex, and cerebellum. CONCLUSIONS: A medial prefrontal response to symptom-provoking stimuli was identified as a common feature of anorexia and bulimia nervosa. This finding supports a conceptualization of eating disorders as being transdiagnostic at the neural level. The abnormal prefrontal reaction is associated with symptom-related material, whereas the occipital and cerebellar differences are nonspecific. An abnormal propensity to activate medial prefrontal circuits in response to inappropriate stimuli is common to eating, obsessive-compulsive, and addictive disorders and may account for the compulsive features of behavior in these conditions.

Adult↗

PubMed2003

The neuronal nitric oxide synthase inhibitor, TRIM, as a neuroprotective agent: effects in models of cerebral ischaemia using histological and magnetic resonance imaging techniques.

Most neuroprotective compounds that appear promising in the pre-clinical phase of testing are subsequently dismissed as relatively ineffective when entered into large-scale clinical trials. Many pre-clinical studies of potential neuroprotective candidates evaluate efficacy in only one or possibly two different models of ischaemia. In this study we examined the effects of 1,2-trifluoromethylphenyl imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor, in three models of cerebral ischaemia (global gerbil, global rat and focal rat). In addition, to follow the progression of the pathology, we also compared traditional histology methods with more advanced magnetic resonance imaging (MRI) as endpoint measures for neurological damage and neuroprotection. TRIM (50 mg/kg i.p.) prevented ischaemia-induced hippocampal damage following global ischaemia in gerbils when administered before or immediately post-occlusion, but failed to protect when administration was delayed until 30 min post-occlusion. Further studies indicated that the compound (administered at 50 mg/kg, i.p., immediately after occlusion) also protected in a rat four-vessel occlusion (4-VO) model using both histological and diffusion-weighted (DW) imaging techniques. In a final study, TRIM (50 mg/kg i.p. 30 min after occlusion) provided a significant reduction in infarct volume at 4 and 24 h as measured using diffusion-weighted (DW) and proton density (PD)-weighted magnetic resonance imaging (MRI). This was confirmed using histological techniques. These studies confirm that nNOS inhibitors may have utility in stroke and provide evidence that combined magnetic resonance and histological methods can provide a powerful method of assessing neuronal damage in rodent models of cerebral ischaemia.

Animals↗

PubMed2003

Recovery and chronicity in anorexia nervosa: brain activity associated with differential outcomes.

BACKGROUND: The course of anorexia nervosa varies from rapid recovery to a chronic debilitating illness. This study aimed to identify functional neural correlates associated with differential outcomes. METHODS: Brain reactions to food and emotional visual stimuli were measured with functional magnetic resonance imaging in nine women who had long-term recovery from restricting anorexia nervosa. These were compared with age- and education-matched groups of eight women chronically ill with restricting anorexia nervosa and nine healthy control women. RESULTS: In response to food stimuli, increased medial prefrontal and anterior cingulate activation, as well as a lack of activity in the inferior parietal lobule, differentiated the recovered group from the healthy control subjects. Increased activation of the right lateral prefrontal, apical prefrontal, and dorsal anterior cingulate cortices differentiated these recovered subjects from chronically ill patients. Group differences were specific to food stimuli, whereas processing of emotional stimuli did not differ between groups. CONCLUSIONS: Separate neural correlates underlie trait and state characteristics of anorexia nervosa. The medial prefrontal response to disease-specific stimuli may be related to trait vulnerability. Lateral and apical prefrontal involvement is associated with a good outcome.

Adult↗

PubMed2003

Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study.

INTRODUCTION: Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects. METHOD: Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured. RESULTS: There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites. CONCLUSIONS: The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.

Adult↗

PubMed2003

Neural abnormalities during cognitive generation of affect in treatment-resistant depression.

BACKGROUND: Dysfunctions in brain regions known to be involved in affect and mood states are thought to be implicated in depression and may have a role in determining the type and symptoms of this illness. METHODS: Functional magnetic resonance imaging was used to elucidate neural correlates of cognitive generation of affect, using a previously published paradigm of evoking affect with picture-caption pairs, in patients with unipolar, treatment-resistant depression. RESULTS: Compared with control participants, patients showed relatively decreased response in the anterior cingulate (rostral; right) with both negative and positive picture-caption pairs and in the medial frontal gyrus and hippocampus (all left) with positive picture-caption pairs. They demonstrated increased response in the inferior (right) and middle temporal gyri (left) with negative picture-caption pairs, and in the parahippocampal gyrus (right), inferior frontal gyrus (left), subgenual cingulate (right), striatum (right), and brain stem (left) with positive picture-caption pairs. CONCLUSIONS: Reduced medial/middle prefrontal and hippocampal activity may account for positive affect disturbances and temporal lobe hyperactivity for negative affect disturbances in treatment-resistant depression. The results also corroborate previous observations from resting positron emission tomography studies and further elucidate the association between hypoactive rostral cingulate and nonresponsiveness to treatment in depression.

Adult↗

PubMed2003

Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers.

BACKGROUND: The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. METHODS: Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. RESULTS: In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. CONCLUSIONS: Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required.

Adult↗

PubMed2003

Task instructions modulate neural responses to fearful facial expressions.

BACKGROUND: The amygdala, hippocampus, ventral, and dorsal prefrontal cortices have been demonstrated to be involved in the response to fearful facial expressions. Little is known, however, about the effect of task instructions upon the intensity of responses within these regions to fear-inducing stimuli. METHODS: Using functional magnetic resonance imaging, we examined neural responses to alternating, 30-sec blocks of fearful and neutral expressions in nine right-handed male volunteers during three different 5-min conditions: 1) passive viewing; 2) performance of a gender-decision task, with no explicit judgment of facial emotion; 3) performance of an emotionality judgment task - an explicitly emotional task. RESULTS: There was a significant effect of task upon activation within the left hippocampus and the left inferior occipital gyrus, and upon the magnitude of response within the left hippocampus, with maximal activation in these regions occurring during passive viewing, and minimal during performance of the explicit task. Performance of the gender-decision and explicit tasks, but not passive viewing, was also associated with activation within ventral frontal cortex. CONCLUSIONS: Neural responses to fearful facial expressions are modulated by task instructions.

Amygdala↗

PubMed2003

Regionally localized thinning of the cerebral cortex in schizophrenia.

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.

Adult↗

PubMed2003

A preferential increase in the extrastriate response to signals of danger.

This study examined neural responses in nine right-handed healthy individuals while they viewed mild and intense expressions of four emotions (fear, disgust, happiness, and sadness) contrasted with neutral faces in four event-related functional magnetic resonance imaging experiments. Orthogonal polynomial trend analysis revealed a significant linear increase in the fusiform extrastriate cortical response to increasing intensities of all four emotional expressions, which was significantly greater to increasing intensities of fear and disgust than happiness and sadness, and a significant linear decrease in response to sadness in another extrastriate region. The amygdala was activated by high-intensity fearful expressions, consistent with findings from previous studies, and by low- but not high-intensity sad expressions. Significant linear increases in response to increasing intensities of fear, disgust, and happiness occurred within the hippocampus, anterior insula, and putamen, respectively. Conversely, significant linear decreases in hippocampal and putamen responses occurred to increasing intensities of sadness. We provide the first demonstration of differential increases in extrastriate and limbic responses to signals of increasing danger than to those of other emotions, and significant decreases in these responses to signals of increasing sadness in others. We suggest that this differential pattern of response to different categories of emotional signals allows the preferential direction of visual attention to signals of imminent danger than to other, less-salient emotional stimuli.

Amygdala↗

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↗

PubMed2003

The effect of negative emotional context on neural and behavioural responses to oesophageal stimulation.

Sensory experience is influenced by emotional context. Although perception of emotion and unpleasant visceral sensation are associated with activation within the insula and dorsal and ventral anterior cingulate gyri (ACG), regions important for attention to and perception of sensory and emotional information, the neural mechanisms underlying the effect of emotional context upon visceral sensation remain unexplored. Using functional MRI, we examined neural responses to phasic, non-painful oesophageal sensation (OS) in eight healthy subjects (seven male; age range 27-36 years) either during neutral or negative emotional contexts produced, respectively, by presentation of neutral or fearful facial expressions. Activation within right insular and bilateral dorsal ACG was significantly greater (P < 0.01) during OS with fearful than with neutral faces. In a second experiment, we measured anxiety, discomfort and neural responses in eight healthy male subjects (age range 22-41 years) to phasic, non-painful OS during presentation of faces depicting either low, moderate or high intensities of fear. Significantly greater (P < 0.01) discomfort, anxiety and activation predominantly within the left dorsal ACG and bilateral anterior insulae occurred with high-intensity compared with low-intensity expressions. Clusters of voxels were also detected in this region, which exhibited a positive correlation between subjective behaviour and blood oxygenation level-dependent effect (P < 0.05). We report the first evidence for a modulation of neural responses, and perceived discomfort during, non-painful visceral stimulation by the intensity of the negative emotional context in which the stimulation occurs, and suggest a mechanism for the effect of negative context on symptoms in functional pain disorders.

Adult↗

PubMed2003

Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations.

BACKGROUND: The neurocognitive basis of auditory hallucinations is unclear, but there is increasing evidence implicating abnormalities in processing inner speech. Previous studies have shown that people with schizophrenia who were prone to auditory hallucinations demonstrated attenuated activation of brain areas during the monitoring of inner speech. AIMS: To investigate whether the same pattern of functional abnormalities would be evident as the rate of inner speech production was varied. METHOD: Eight people with schizophrenia who had a history of prominent auditory hallucinations and eight control participants were studied using functional magnetic resonance imaging while the rate of inner speech generation was varied experimentally. RESULTS: When the rate of inner speech generation was increased, the participants with schizophrenia showed a relatively attenuated response in the right temporal, parietal, parahippocampal and cerebellar cortex. CONCLUSIONS: In people with schizophrenia who are prone to auditory hallucinations, increasing the demands on the processing of inner speech is associated with attenuated engagement of the brain areas implicated in verbal self-monitoring.

Adult↗

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

Speechreading circuits in people born deaf.

In hearing people, silent speechreading generates bilateral activation in superior temporal regions specialised for the perception of auditory speech [Science 276 (1997) 593; Neuroreport 11 (2000) 1729; Proceedings of the Royal Society London B 268 (2001) 451]. In the present study, FMRI data were collected from deaf and hearing volunteers while they speechread numbers and during a control task in which they counted nonsense mouth movements (gurns). Brain activation for silent speechreading in oral deaf participants was found primarily in posterior cingulate cortex and hippocampal/lingual gyri. In contrast to the pattern observed in the hearing group, deaf participants showed no speechreading-specific activation in left lateral temporal regions. These data suggest that acoustic experience shapes the functional circuits for analysing speech. We speculate on the functional role, the posterior cingulate gyrus may play in speechreading by profoundly congenitally deaf people.

Acoustics↗