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Biomedical subjects

Michael D Hunter

Publications and source records attributed to Michael D Hunter.

16 recordsLinked to original sources
PubMed2006

Endoscopic mucosal resection for flat neoplasia in chronic ulcerative colitis: can we change the endoscopic management paradigm?

BACKGROUND: The potential of endoscopic mucosal resection (EMR) for treating flat dysplastic lesions in chronic ulcerative colitis (CUC) has not been addressed so far. Historically, such lesions were referred for colectomy. Furthermore, there are only limited data to support endoscopic resection of exophytic adenoma-like mass (ALM) lesions in colitis. AIMS: To evaluate the safety and clinical outcomes of patients with colitis undergoing EMR for Paris class 0-II and class I ALM compared with sporadic controls. Secondary aims were to re-evaluate the prevalence, anatomical "mapping" and histopathological characteristics of both Paris class 0-II and class I lesions in the context of CUC. METHODS: Prospective clinical, pathological and outcome data of patients with colitis-associated Paris class 0-II and Paris class I ALM treated with EMR (primary end points being colorectal cancer development, resection efficacy, metachronous lesion rates and post-resection recurrence rates) were compared with those of sporadic controls. RESULTS: 204 lesions were diagnosed in 169 patients during the study period: 167 (82%) diagnosed at "entry" colonoscopy, and 36 (18%) diagnosed at follow-up. 170 ALMs, 18 dysplasia-associated lesion masses (DALMs) and 16 cancers were diagnosed. A total of 4316 colonoscopies were performed throughout the study period (median per patient: 6; range: 1-8). The median follow-up period for the complete cohort was 4.1 years (range: 3.6-5.21). 1675 controls were included from our prospective database of patients without CUC who had undergone EMR for sporadic Paris class 0-II and snare polypectomy of Paris type I lesions from 1998 onwards, and were considered to be at moderate to high lifetime risk of colorectal cancer. 3792 colonoscopies were performed throughout the study period in this group (median per patient: 4; range: 1-7). The median follow-up period was 4.8 years (range: 2.9-5.2). No statistically significant differences were observed between the CUC study group and controls with respect to age, sex, median number of colonoscopies per patient, median follow-up duration, post-resection complications, median lesional diameter or interval cancer rates. However, there was a significant between-group difference regarding the prevalence of Paris class 0-II lesions in the CUC group (82/155 (61%)) compared with controls (285/801 (35%); chi(2) = 31.13; p<0.001). Furthermore, recurrence rates of lateral spreading tumours were higher in the colitis cohort (1/7 (14%)) than among controls (0/10 (0%); p = 0.048 (95% CI 11.64% to 40.21%)). CONCLUSIONS: Flat DALM, similarly to Paris class I ALM, can be managed safely by EMR in CUC. A change in management paradigm to include EMR for the resection of flat dysplastic lesions in selected cases is proposed.

Adenoma↗
PubMed2006

A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery.

OBJECTIVE: Difficulty with social interactions is a characteristic of schizophrenia. The authors used functional magnetic resonance imaging (fMRI) to investigate brain activation changes during a social cognition paradigm in patients with schizophrenia during and after an acute episode and their association with social and executive function. METHOD: In a longitudinal study design, 14 patients with schizophrenia experiencing an acute episode had an fMRI scan. They returned for a follow-up scan after clinical improvement. Fourteen healthy comparison subjects were also scanned twice with approximately the same time interval between scans as in the patient group. The authors employed a social cognition fMRI paradigm involving empathic and forgivability judgments. Schizophrenia symptoms, social functioning and illness insight scales, and the Wisconsin Card Sorting Test were used to examine whether improvement on these measures was associated with recovery of brain activation in response to the social cognition paradigm. RESULTS: After recovery from the acute episode, patients exhibited increased activation in the left medial prefrontal cortex, which was, in turn, significantly correlated with improved insight and social functioning. Decreased symptom severity and improved performance on the Wisconsin Card Sorting Test were not significantly associated with increased left medial prefrontal cortex activation. CONCLUSIONS: This is the first study to the authors' knowledge to use a social cognition paradigm to reveal improved left medial prefrontal cortex activation in schizophrenia after recovery from an acute episode. These results suggest that restored left medial prefrontal cortex activation may mediate improvement of insight and social functioning in patients with schizophrenia.

Adult↗
PubMed2006

Impact of modafinil on prefrontal executive function in schizophrenia.

OBJECTIVE: The purpose of this study was to investigate the acute effects of modafinil on prefrontal activation and cognitive control of motor activity in people with schizophrenia and prominent negative symptoms. METHOD: In a crossover design, 12 subjects with schizophrenia were studied twice, receiving either modafinil or placebo prior to functional magnetic resonance imaging (fMRI). Inside the scanner, they performed a task probing cognitive control that required deliberate variation of motor activity in time. RESULTS: Modafinil administration was associated with significantly greater activation of the dorsolateral prefrontal cortex during fMRI. Its physiological and behavioral effects were correlated. This was most evident in individuals with worse baseline executive function. Focal response to modafinil in the left dorsolateral prefrontal cortex and baseline letter fluency scores predicted most of the variance in the drug's effect on cognitive control. CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients. Increased activation in the dorsolateral prefrontal cortex and in neuropsychological performance were observed in patients with suboptimal baseline function.

Adult↗
PubMed2006

Modafinil and unconstrained motor activity in schizophrenia: double-blind crossover placebo-controlled trial.

Avolition affects quality of life in chronic schizophrenia. We investigated the effect of modafinil upon unconstrained motor activity in 18 male patients. In a randomised crossover design study, wrist-worn actigraphic monitors were used to objectively record motor activity over a 20 h period. Patients' total activity was significantly greater when given the drug. These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition.

Benzhydryl Compounds↗
PubMed2005

Quantifiable change in functional brain response to empathic and forgivability judgments with resolution of posttraumatic stress disorder.

Previous functional neuroimaging studies of posttraumatic stress disorder (PTSD) have mainly focused on symptom-provocation paradigms in combat-related PTSD. We sought to elucidate the effect of non-combat-related PTSD on the physiology of social cognition. Thirteen patients with PTSD underwent functional magnetic resonance imaging (fMRI) while they engaged in tasks that (i) involve speculation on another's intention, (ii) invoke empathy and (iii) involve making judgments of the forgivability of others' actions; each versus 'baseline' social reasoning judgments. A post-therapy fMRI scan followed a course of modified cognitive behavioural therapy. Post-therapy, we found increased activation in brain regions predicted on the basis of foregoing work in healthy subjects. These included significant left middle temporal gyrus activation in post-therapy response to empathy judgments and posterior cingulate gyrus activation in post-therapy response to forgivability judgments. The specific regions of the human brain activated by empathy and forgivability judgments changed with symptom resolution in PTSD. Time and therapy are likely contributory factors that lead to a degree of 'normalisation' of the neural response to these social cognition tasks.

Adult↗
PubMed2005

Male and female voices activate distinct regions in the male brain.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Acoustic Stimulation↗
PubMed2005

The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective "back-to-back" endoscopic study.

BACKGROUND: In hereditary nonpolyposis colorectal cancer flat and diminutive adenomas occur, particularly in the right colon. Such lesions may assume a high risk of malignant transformation. Interval cancers are known to occur in this group. Chromoscopic colonoscopy enhances detection in patients assuming a moderate to high lifetime risk of colorectal cancer. AIM: To prospectively assess the efficacy of high-magnification-chromoscopic colonoscopy for the detection of neoplastic lesions in patients undergoing hereditary nonpolyposis colorectal cancer screening. METHODS: Twenty-five asymptomatic patients fulfilling modified Amsterdam criteria underwent "back-to-back" colonoscopy. Conventional colonoscopy with targeted chromoscopy was performed initially followed by pan-colonic chromoscopic colonoscopy. Diagnostic extubation times and volumes of normal saline and indigo carmine (IC) were controlled. RESULTS: Using conventional colonoscopy and targeted chromoscopy 24 lesions were detected in 13 patients (20 exophytic/4 flat). Pan-colonic chromoscopy identified a further 52 lesions in 16 patients (17 exophytic/35 flat). Pan-chromoscopy identified significantly more adenomas than conventional colonoscopy (p= 0.001) and a significantly high number of flat adenomas (p= 0.004). CONCLUSIONS: Pan-colonic chromoscopic colonoscopy improves detection of significant neoplastic lesions in hereditary nonpolyposis colorectal cancer screening. Pan-chromoscopy may help better stratify colorectal cancer "risk" in this cohort and aid planning of surveillance colonoscopic follow-up.

Adult↗
PubMed2005

Structural brain correlates of unconstrained motor activity in people with schizophrenia.

Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

Adult↗
PubMed2004

Gender-specific sensitivity to low frequencies in male speech.

The perception of human voices as naturally occurring sound objects may correspond to the detection of specific components of the frequency spectrum. In the current study, a psychophysical experiment was undertaken to investigate whether male and female listeners differed with respect to which frequencies were important in the perception of a male voice as a natural sound object. For females (but not males) the presence of low frequencies (<220 Hz), but not high frequencies (>4 kHz), was most crucial in the perception of a male voice as natural. This finding could be compatible with a neuroethological interpretation: low frequencies in the range that were studied are important in distinguishing male from female voices and mature from immature male voices.

Adult↗
PubMed2004

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.

Adult↗
PubMed2004

Spatial and temporal dissociation in prefrontal cortex during action execution.

It is widely accepted that dorsolateral prefrontal cortex (DLPFC) is activated at the time of action generation in humans. However, the previous functional neuroimaging studies that have supported this hypothesis temporally integrated brain dynamics and therefore could not demonstrate when DLPFC underwent activation relative to the emergence of voluntary behavior. Data that are time-locked to the instant of voluntary action execution do not reveal DLPFC activation at that moment. Rather, activated foci are seen at the frontal poles. We investigated this apparent conundrum through three differentially constrained experiments, utilizing functional magnetic resonance imaging to identify those prefrontal areas exhibiting functional change at the moment of spontaneous action execution. We observed profound functional dissociation between anterior and dorsolateral regions, compatible with their involvement at different points during the temporal evolution of action: bilaterally the frontal poles activated at the moment of execution, while simultaneously (and relative to a prior activation state) left DLPFC 'deactivated.'

Adult↗
PubMed2003

Approaching an ecologically valid functional anatomy of spontaneous "willed" action.

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous "willed" action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding "which" of two buttons to press, and "when" to press them, subjects generated sequences of action that were of high information content ("novelty" or "randomness"). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate "higher" regions from subordinate motor areas.

Adult↗
PubMed2003

A neural basis for the perception of voices in external auditory space.

We used functional imaging of normal subjects to identify the neural substrate for the perception of voices in external auditory space. This fundamental process can be abnormal in psychosis, when voices that are not true external auditory objects (auditory verbal hallucinations) may appear to originate in external space. The perception of voices as objects in external space depends on filtering by the outer ear. Psychoses that distort this process involve the cerebral cortex. Functional magnetic resonance imaging was carried out on 12 normal subjects using an inside-the-scanner simulation of 'inside head' and 'outside head' voices in the form of typical auditory verbal hallucinations. Comparison between the brain activity associated with the two conditions allowed us to test the hypothesis that the perception of voices in external space ('outside head') is subserved by a temperoparietal network comprising association auditory cortex posterior to Heschl's gyrus [planum temporale (PT)] and inferior parietal lobule. Group analyses of response to 'outside head' versus 'inside head' voices showed significant activation solely in the left PT. This was demonstrated in three experiments in which the predominant lateralization of the stimulus was to the right, to the left or balanced. These findings suggest a critical involvement of the left PT in the perception of voices in external space that is not dependent on precise spatial location. Based on this, we suggest a model for the false perception of externally located auditory verbal hallucinations.

Acoustics↗
PubMed2003

Laterality effects in perceived spatial location of hallucination-like voices.

Aydin and colleagues reported a reversal of physiological 'right-ear advantage' in a group of right-handed patients with schizophrenia, using an auditory acuity test. In schizophrenia, auditory hallucinations may appear to be spatially located inside or outside the patient's head. Here we show, using virtual acoustic space techniques, that normal right-handed subjects have a right-ear advantage for correctly locating the 'source' of hallucination-like voices as from either inside or outside the head. We propose a model for understanding lateralised, external hallucinations in schizophrenia based upon reversal of normal cortical asymmetry for auditory spatial processing.

Adult↗
PubMedDate not supplied

Locating voices in space: a perceptual model for auditory hallucinations?

INTRODUCTION: Auditory hallucinations are often perceived as being located in external auditory space ("outside the head"), like real auditory perceptions, but in the absence of a speaker or other external stimulus. METHOD: A selective literature review of the spatial phenomenology of auditory hallucinations and the cognitive neuroscience of locating real voices in external space was undertaken. An auditory-perceptual model of external auditory hallucinations was developed in healthy right-handed subjects using functional magnetic resonance imaging and the presentation of speech in virtual acoustic space. RESULTS: Karl Jaspers inextricably linked "reality" and "externality" of auditory hallucinations. Although these two properties do not always occur simultaneously in hallucinating patients, the issue of "externality" is important from both a clinical and neuroscientific perspective. In an auditory-perceptual model of auditory hallucinations, association cortex in the left planum temporale is critically involved in the perception of real voices as located in external space. Right-sided voice stimuli are associated with greater neural response in the dominant (left) auditory cortex than left-sided stimuli. Subjects are better at identifying the spatial location of voices presented on the right than on the left. CONCLUSION: The auditory-perceptual model described helps identify candidate brain systems likely to be involved in the pathogenesis of auditory hallucinations in schizophrenia, and is distinct from other models, which use concepts of "internal monitoring" and "inner speech". Its application, in the cognitive neuroscientific investigation of the phenomenology of auditory hallucinations, may shed further light on the mechanisms underlying this distressing experience.

Journal Article↗