[show abstract][hide abstract] ABSTRACT: Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness.
[show abstract][hide abstract] ABSTRACT: Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as "harmless" or "threatening." Individuals' stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, "threatening," compared with "harmless" behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl's gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual's propensity to assess stimuli as "threatening." SCRs may modulate cognitive assessments on a "harmless-threatening" dimension, thereby modulating affective tone and hence behavior.
Frontiers in Human Neuroscience 01/2012; 6:349. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: The perception and judgement of social hierarchies forms an integral part of social cognition. Hierarchical judgements can be either self-referential or allocentric (pertaining to two or more external agents). In psychiatric conditions such as dissocial personality disorder and schizophrenia, the impact of hierarchies may be problematic. We sought to elucidate the brain regions involved in judging allocentric social hierarchies. Twenty-two healthy male subjects underwent three fMRI scans. During scanning, subjects answered questions concerning visually-presented target pairs of human individual's relative superiority within a specific social hierarchy or their perceived degree of social alliance (i.e., whether they were "friends or enemies"). Subjects also made judgements relating to target pairs' age, gender and fame to control for confounding factors and performed a baseline numerical task. Response times increased in line with hypothesized ascending executive load. Both social hierarchy and social alliance judgements activated left ventrolateral prefrontal cortex (VLPFC), left dorsal inferior frontal gyrus (IFG) and bilateral fusiform gyri. In addition, social alliance judgements activated right dorsal IFG and medial prefrontal cortex. When compared directly with social alliance, social hierarchy judgements activated left orbitofrontal cortex. Detecting the presence of social hierarchies and judging other's relative standing within them implicates the cognitive executive, in particular the VLPFC. Our finding informs accounts of 'normal' social cognition but our method also provides a means of probing the dissocial brain in personality disorder and schizophrenia where executive function may be dysfunctional.
[show abstract][hide abstract] ABSTRACT: Investigating auditory hallucinations that occur in health may help elucidate brain mechanisms which lead to the pathological experience of auditory hallucinations in neuropsychiatric disorders such as schizophrenia. In this study, we investigated healthy individuals who reported auditory hallucinations whilst falling asleep (hypnagogic hallucinations; HG) and waking up (hypnopompic hallucinations; HP). In an initial behavioural study, we found that subjects with a history of auditory HG/HP hallucinations (n = 26) reported significantly greater subjective sensitivity to environmental sounds than non-hallucinator controls (n = 74). Then, two fMRI experiments were performed. The first examined speech-evoked brain activation in 12 subjects with a history of auditory HG/HP hallucinations and 12 non-hallucinator controls matched for age, gender and IQ. The second fMRI experiment, in the same subjects, probed how brain activation was modulated by auditory attention using a bimodal selective attention paradigm. In the first experiment, the hallucinator group demonstrated significantly greater speech-evoked activation in the left supramarginal gyrus than the control group. In the second experiment, directing attention towards the auditory (vs. visual) modality induced significantly greater activation of the anterior cingulate gyrus in the hallucinator group than in the control group. These results suggest that hallucination proneness is associated with increased sensitivity of auditory and polysensory association cortex to auditory stimulation, an effect which might arise due to enhanced attentional bias from the anterior cingulate gyrus. Our data support the overarching hypothesis that top-down modulation of auditory cortical response characteristics may be a key mechanistic step in the generation of auditory hallucinations.
[show abstract][hide abstract] ABSTRACT: Our ability to interact physically with objects in the external world critically depends on temporal coupling between perception and movement (sensorimotor timing) and swift behavioral adjustment to changes in the environment (error correction). In this study, we investigated the neural correlates of the correction of subliminal and supraliminal phase shifts during a sensorimotor synchronization task. In particular, we focused on the role of the cerebellum because this structure has been shown to play a role in both motor timing and error correction. Experiment 1 used fMRI to show that the right cerebellar dentate nucleus and primary motor and sensory cortices were activated during regular timing and during the correction of subliminal errors. The correction of supraliminal phase shifts led to additional activations in the left cerebellum and right inferior parietal and frontal areas. Furthermore, a psychophysiological interaction analysis revealed that supraliminal error correction was associated with enhanced connectivity of the left cerebellum with frontal, auditory, and sensory cortices and with the right cerebellum. Experiment 2 showed that suppression of the left but not the right cerebellum with theta burst TMS significantly affected supraliminal error correction. These findings provide evidence that the left lateral cerebellum is essential for supraliminal error correction during sensorimotor synchronization.
Journal of Cognitive Neuroscience 05/2010; 23(5):1100-12. · 4.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: The clock drawing (CD) task involves visual integration skills associated with parietal lobe function. Seven mild Alzheimer's Disease (AD) patients and 11 healthy elderly controls (EC) underwent functional magnetic resonance imaging (fMRI) scanning while viewing a radial motion (RM) task. This RM task in EC activated the bilateral secondary visual cortex and parietal regions, whereas AD patients activated only the right-sided secondary visual cortex. The magnitude of the fMRI signal in the left superior parietal lobe was positively correlated with performance on the CD task in AD patients. These findings suggest that complex visuospatial processing impairments reflect the underlying AD neuropathology in parietal regions.
The International journal of neuroscience 05/2010; 120(5):335-43. · 0.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Visuospatial impairments are known to occur in Alzheimer's disease (AD). We hypothesised that functional magnetic resonance imaging (fMRI) response in task-related brain regions would be impaired in patients with AD during the task and that treatment with acetyl cholinesterase inhibitors would enhance activations in brain regions concerned with this visual perceptual processing.
Ten AD subjects were neuropsychologically assessed and underwent fMRI imaging whilst performing a series of visuospatial perception tasks, before and after treatment with acetyl cholinesterase inhibitors. Eleven healthy elderly comparison subjects were also scanned twice.
Regions of increased brain activation in AD included the left precuneus, left cuneus, left supramarginal gyrus, right parieto-temporal cortex and right inferior parietal lobule. Further, increased activation in the left precuneus was found to correlate significantly with improved functioning of activities of daily living.
We believe this to be the first fMRI study that, after controlling for the confound of repeat scanning, demonstrates altered patterns of brain activation associated with visuospatial processing following treatment in patients with AD. The treatment-related improvement of visual perception in AD may rely on enhanced attentional mechanisms, thereby possibly supporting independent living through improvement on activities of daily living.
[show abstract][hide abstract] ABSTRACT: In the executive model of deception, the telling of a lie necessitates the inhibition of a veridical prepotent response (the truth), and such inhibition incurs a temporal penalty, manifest as a longer response time. If memory processes are engaged in generating such truths, then memory function should affect truthful and deceptive response times. To investigate this we examined the relationship between performance on a semantic knowledge deception task and a test of verbal memory in 40 college students. We found that verbal memory performance differentially affects the temporal parameters of truth and deception.
The American Journal of Psychology 01/2010; 123(4):447-53. · 1.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The neural basis of visuospatial deficits in Alzheimer's disease is unclear. We wished to investigate the neural basis of visuospatial perception in patients with Alzheimer's disease compared with healthy elderly comparison subjects using functional magnetic resonance imaging (fMRI). Twelve patients with AD and thirteen elderly comparison subjects were investigated. The patients were recruited from the local clinic and comparison subjects were from spouses and community. All participants underwent fMRI whilst viewing visuospatial stimuli and structural MRI, and findings were analysed using voxel-based morphometry. The comparison group activated V5, superior parietal lobe, parieto-occipital cortex and premotor cortices. The AD group demonstrated hypoactivation in the above regions and instead showed greater activation in inferior parietal lobule and activated additional areas. There was no structural atrophy above and beyond that found globally in patients in the identified regions of BOLD activation. To our knowledge, this is the first study to explore the neuroanatomy of perception of depth and motion in Alzheimer's disease. These specific functional deficits in AD provide evidence for an underlying patho-physiological basis for the clinically important symptom of visuospatial disorientation in patients with AD.
Psychiatry Research 06/2009; 172(2):109-16. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Limited behavioural repertoire impacts quality of life in chronic schizophrenia. We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. However, increased movement in itself may be of limited clinical significance. Hence, we sought to analyse the 'structure' of spontaneous movement in patients with schizophrenia and to examine whether the chunking of spontaneous activity has a neuroanatomical basis. 'Actiwatches' were used to record spontaneous motor activity over a 20 hour period in sixteen male patients with schizophrenia. Time-series data were analysed for the number of discrete spontaneous activities, which might indicate a degree of structure to ongoing activity. Subjects underwent a whole-brain structural MRI scan. The 'number of discrete movement epochs' correlated with volumes of regions within bilateral rostro-ventral putamen and temporal poles. These data suggest that in people with schizophrenia the volume of bilateral putamen may influence the complexity of their behaviours, as distinct from the overall amount of behaviour. The results are presented in the context of a large body of previous research examining the role of the basal ganglia in motor and cognitive pattern generation.
[show abstract][hide abstract] ABSTRACT: To identify factors significantly associated with post-traumatic stress disorder (PTSD), anxiety, and depression at 3 months post-injury; to develop a generic model to predict the occurrence of PTSD, anxiety, and depression at 3 months post-injury; and to validate this model in a test data set of patients.
Prospective cohort study.
Participants were 823 patients attending an emergency department (ED) following accidental injury. Baseline questionnaires were completed, with 1 and 3 months postal follow-ups. Predictor variables demonstrating significant associations with two of the three outcome measures (3-month HAD anxiety and depression scores and PTSD symptoms) were included in multivariate regression models for each outcome. Non-significant predictor variables were removed until all remaining independent variables made the most significant contribution to each of the three models. Models were validated using a test dataset.
Previous history of mental health problems, neuroticism score and having PTSD symptoms at 1 month predicted adverse outcomes at 3 months. When used on the test datasets, the areas under the receiver operating curve (ROC) curve for the models predicting outcomes at 3 months were: PTSD=0.91 (sensitivity=88.5%); anxiety=0.87 (sensitivity=93.7%); and depression=0.87 (sensitivity=96.7%).
The final model performed moderately well across the three outcomes and may be useful clinically as a generic rule-out tool to identify those who will not require follow up, watchful waiting or intervention.
British Journal of Clinical Psychology 10/2008; 48(Pt 1):31-45. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.
[show abstract][hide abstract] ABSTRACT: Schizophrenia is a severe, chronic, often disabling mental illness with onset characteristically in early adulthood. This article reviews the historical concepts of schizophrenia by Kraepelin and Bleuler, and discusses recent developments in the aetiology of schizophrenia, with an emphasis on the interplay between biological, psychological, and social factors. Genetic factors play an important role in the aetiology, as they ‘programme’ the early development of the brain’s structure, including the neurotransmitter receptor systems. According to the stress–vulnerability model, environmental stress and high ‘expressed emotion’ can precipitate the onset as well as influence the course and outcome of the illness. Cannabis abuse has a significant impact on the risk of schizophrenia, particularly in individuals with biological vulnerability to develop the illness. Clinically, patients with schizophrenia present with symptoms comprising positive (first-rank) and negative symptoms.
[show abstract][hide abstract] ABSTRACT: The management of dysplasia-associated lesional mass (DALM) and adenoma-like mass (ALM) in chronic ulcerative colitis (CUC) differs radically, involving total pan-proctocolectomy vs endoscopic resection and surveillance. Such lesions cannot be reliably differentiated using conventional colonoscopy. Confocal laser scanning imaging enables in vivo surface and subsurface cellular resolution imaging during ongoing video endoscopy. The aim of this study was to prospectively assess the clinical applicability and predictive power of the Pentax EC3870K endomicroscope for the in vivo differentiation of ALM and DALM in CUC during ongoing videocolonoscopy.
Patients were recruited who had a diagnosis of ALM or DALM within the previous 16 weeks. Confocal laser endomicroscopic (CLE) imaging of the circumscribed lesion and 4 adjacent mucosal segments was performed. Targeted biopsy with and without tissue sampling with endoscopic mucosal resection was performed and compared with conventional histopathology as the gold standard.
Thirty-six patients with 36 lesions fulfilled the study entry criteria. Using modified Mainz criteria for the in vivo diagnosis of ALM and DALM, the kappa coefficient of agreement between CLE and histopathologic evaluation was 0.91, and accuracy was 97% (95% confidence interval = 86%-99%).
This is the first study addressing the novel application of the Pentax EC3870K endomicroscopy system for the in vivo differentiation of ALM and DALM during ongoing video colonoscopy in CUC. We have shown that ALM and DALM can be differentiated with a high overall accuracy, enabling the safe selection of patients suitable for endoluminal resection versus immediate referral for pan-proctocolectomy.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11/2007; 5(10):1235-41. · 5.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study, we investigated the mechanism for the left cerebral hemisphere's dominance for speech perception. We utilized the crossover of auditory pathways in the central nervous system to present speech stimuli more directly to the left hemisphere (via the right ear) and right hemisphere (via the left ear). Using functional MRI, we found that estimated duration of neural response in the left auditory cortex increased as more speech information was directly received from the right ear. Conversely, response duration in the right auditory cortex was not modulated when more speech information was directly received from the left ear. These data suggest that selective temporal responding distinguishes the dominant from nondominant hemisphere of the human brain during speech perception.
[show abstract][hide abstract] ABSTRACT: Familiarity with a speaker's voice has been shown to enhance its auditory processing, implicating physiological effects at the level of the auditory cortex, although auditory cortical involvement has not previously been demonstrated. Eleven healthy right-handed male participants performed two tasks during blood oxygenation level-dependent functional MRI at 1.5 T. Both tasks used the same vocal stimuli. In task 1, they classified speakers as familiar or unfamiliar. In task 2, they judged stimuli as being in the right or left auditory field. Our analysis showed an area of auditory cortex on the lower bank of the superior temporal sulcus that was preferentially activated by familiar voices in both tasks. Familiar voices may elicit access to detailed sensory expectations, allowing enhanced auditory cortical processing.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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%)).
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.
[show abstract][hide abstract] ABSTRACT: Flat and depressed neoplastic lesions of the colorectum [Paris type (PT) 0-II] localized to the superficial submucosal (sm) layer can be managed using endoscopic mucosal resection. Successful endoluminal management can be enhanced using endoscopic or ultrasound tools that help predict the degree of sm invasion. Previous studies addressing invasive depth estimation using high-magnification chromoscopic colonoscopy showed a low specificity for deep sm layer 3 invasion with miniprobe ultrasound demonstrating better nodal and T stage in vivo prediction. High-resolution vascular mapping of lesions can show microvascular superficial changes that may predict sm invasive disease.
Vascular mapping in combination with high-magnification chromoscopic colonoscopy (HMCC) may provide an accurate tool for the invasive depth estimation of PT type II neoplastic lesions as compared with high frequency 20/12.5 MHz miniprobe ultrasound.
Sixty-eight patients with a known diagnosis of PT II neoplasia were imaged using 3 "back to back" imaging modalities. Phase 1-vascular ectasia mapping; phase 2-HMCC with crypt analysis according to Nagata criteria; phase 3-12.5/20 MHz miniprobe ultrasound. Lesions predicted as T0/1/N0 were resected using endoscopic mucosal resection with the remaining referred for surgery. Each imaging modality was then compared with the resected histopathologic specimen used as the "gold standard."
N=68 lesions (19 sm1/13 sm2/36 sm3). Overall accuracy of Nagata criteria, Nagata criteria combined with vascular mapping, and ultrasound staging was 65%, 78%, and 94%, respectively (P<0.001) when observing the between phase differences. Fifty-two lesions were resected surgically. The prevalence of node positive disease was 16% (8/52) with the remaining 44/52 (84%) being confirmed pN0 at histopathology. The kappa coefficient of agreement between invasive depth estimation (using histopathology as the gold standard), Nagata stage, Nagata stage plus vascular ectasia mapping and ultrasound stage was 0.47, 0.65, and 0.9, respectively. A significant improvement in between phase differences was observed (P=0.001).
This is the first study to address the in vivo clinical utility of vascular mapping in combination with HMCC for the T and N staging of PT II neoplasia. Combination imaging may provide an adequate clinical tool for both T and N stage assessment in vivo and help stratify those patients at high risk for T2/N1 disease that may benefit from further high-frequency miniprobe ultrasound (HFUS) assessment and possible primary surgical excision. This is important in the clinical context, given the high overall costs of a second HFUS examination, limitation of HFUS resources, and safe selection of patients undergoing primary endoscopic resection versus surgical resection.
Journal of Clinical Gastroenterology 03/2007; 41(2):178-84. · 3.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 01/2007; 163(12):2184-6. · 14.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
The British Journal of Psychiatry 12/2006; 189:461-2. · 6.61 Impact Factor