Michael D. Hunter

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.

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.

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%); χ2 = 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.

The state of tranquility: Subjective perception is shaped by contextual modulation of auditory connectivity

In this study, we investigated brain mechanisms for the generation of subjective experience from objective sensory inputs. Our experimental construct was subjective tranquility. Tranquility is a mental state more likely to occur in the presence of objective sensory inputs that arise from natural features in the environment. We used functional magnetic resonance imaging to examine the neural response to scenes that were visually distinct (beach images vs. freeway images) and experienced as tranquil (beach) or non-tranquil (freeway). Both sets of scenes had the same auditory component because waves breaking on a beach and vehicles moving on a freeway can produce similar auditory spectral and temporal characteristics, perceived as a constant roar. Compared with scenes experienced as non-tranquil, we found that subjectively tranquil scenes were associated with significantly greater effective connectivity between the auditory cortex and medial prefrontal cortex, a region implicated in the evaluation of mental states. Similarly enhanced connectivity was also observed between the auditory cortex and posterior cingulate gyrus, temporoparietal cortex and thalamus. These findings demonstrate that visual context can modulate connectivity of the auditory cortex with regions implicated in the generation of subjective states. Importantly, this effect arises under conditions of identical auditory input. Hence, the same sound may be associated with different percepts reflecting varying connectivity between the auditory cortex and other brain regions. This suggests that subjective experience is more closely linked to the connectivity state of the auditory cortex than to its basic sensory inputs.

The neural basis of visuospatial perception in Alzheimer's disease and healthy elderly comparison subjects: An fMRI study

The neural basis of visuospatial deficits in Alzheimers disease is unclear. We wished to investigate the neural basis of visuospatial perception in patients with Alzheimers 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 Alzheimers 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.

The role of the cerebellum in sub-and supraliminal error correction during sensorimotor synchronization: Evidence from fmri and tms

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.

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.

Recent Developments in Deception Research

Lying and deception are common human activities and may occur in a wide variety of clinical contexts. These behaviours implicate higher neural systems within the brains of humans and other primates. Recent functional neuroimaging studies suggest that prefrontal and anterior cingulate cortices are particularly engaged during certain forms of deception, hence, that executive processes support deceit. Congruent with the latter position is the finding that lies take longer to execute than truthful responses. To date, no functional neuroimaging study has demonstrated brain regions exhibiting greater activation during truth telling (compared with lying). Although the latter may reflect a Type II error, it also supports the hypothesis that truthfulness comprises a relative baseline in human cognition and communication. Those psychiatric disorders particularly associated with the practice of deception are varied both in aetiology and the degree to which deceit is central to their conceptualisation. Nevertheless, the deceiving human is likely to be engaging components of their cognitive executive system, a proposal with implications for societal notions of responsibility and mitigation. A successful lie denotes a functioning executive.

The Neural Correlates of Emotion Regulation by Implementation Intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.

Enhanced cortical effects of auditory stimulation and auditory attention in healthy individuals prone to auditory hallucinations during partial wakefulness.

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.