Edson Amaro

Misattribution of speech and impaired connectivity in patients with auditory verbal hallucinations

Several studies report that patients with schizophrenia who experience auditory verbal hallucinations (AVH) tend to misidentify their own speech as that of somebody else. We tested the hypothesis that this tendency is associated with poor functional integration within the network of regions that mediate the evaluation of speech. Using functional magnetic resonance imaging, we measured brain responses from 11 schizophrenics with AVH, 10 schizophrenics without AVH, and 10 healthy controls. Stimuli comprised prerecorded words, which varied for their source (self, alien) and acoustic quality (undistorted, distorted). Participants had to indicate whether each word was spoken in their own or another persons voice via a button press. Using dynamic causal modeling, we estimated the impact of one region over another (“effective connectivity”) and how this was modulated by source and distortion. In controls and in patients without AVH, the connectivity between left superior temporal and anterior cingulate cortex was significantly greater for alien‐ than for self‐generated speech; in contrast, the reverse trend was found in schizophrenic patients with AVH. In conclusion, when patients with AVH appraise their own speech we find impaired functional integration between left superior temporal and anterior cingulate cortex. Although this finding is based on external rather than internal speech, the same mechanism may contribute to the faulty appraisal of inner speech that putatively underlies AVH. Hum Brain Mapp 2007.

Performing functional magnetic resonance imaging in patients with Parkinson's disease treated with deep brain stimulation

Deep brain stimulation (DBS) is a relatively novel treatment in advanced Parkinsons disease (PD). Functional magnetic resonance imaging (fMRI) is a useful technique for examining the effects of DBS both within the basal ganglia and its cortical connectivity. There are technical difficulties in imaging patients with PD, and the DBS itself can generate image artifacts. We describe aspects related to optimizing the fMRI acquisition parameters in patients with DBS and the results of sensorimotor activation tasks performed by four PD patients during hand, foot, and tongue movements, both before and after DBS implant. Provided that all safety conditions are followed, it is possible to perform fMRI in patients with PD and DBS. The standard DBS surgical procedure has to be slightly modified in order to reduce image artifacts. The event‐related design provided increased power to detect sensorimotor cortex and basal ganglia activation.

Faulty Suppression of Irrelevant Material in Patients with Thought Disorder Linked to Attenuated Frontotemporal Activation

Formal thought disorder is a feature schizophrenia that manifests as disorganized, incoherent speech, and is associated with a poor clinical outcome. The neurocognitive basis of this symptom is unclear but it is thought to involve an impairment in semantic processing classically described as a loosening of meaningful associations. Using a paradigm derived from the n400 event-related, potential, we examined the extent to which regional activation during semantic processing is altered in schizophrenic patients with formal thought disorder. Ten healthy control and 18 schizophrenic participants (9 with and 9 without formal thought disorder) performed a semantic decision sentence task during an event-related functional magnetic resonance imaging experiment. We employed analysis of variance to estimate the main effects of semantic congruency and groups on activation and specific effects of formal thought disorder were addressed using post-hoc comparisons. We found that the frontotemporal network, normally engaged by a semantic decision task, was underactivated in schizophrenia, particularly in patients with FTD. This network is implicated in the inhibition of automatically primed stimuli and impairment of its function interferes with language processing and contributes to the production of incoherent speech.

Preliminary functional magnetic resonance imaging Stroop task results before and after a Zen meditation retreat

FOR MANY CENTURIES, Asian philosophers have affirmed that there are different states of awareness to be developed through meditation. Meditation results in changes in cognition, sensory perception, affect, hormones, and autonomic activity. Until today, there have been very few imaging studies of the neural correlates of meditation. Most of them study the act of meditation by experienced meditators during image acquisition. Functional magnetic resonance imaging (fMRI) has the ability to collect anatomical and functional data and has better resolution compared to positron emission tomography and single photon emission computed tomography. The intense noise of the machine and the obligatory prone position are not the best environment for the study of meditation practice in the MR machine. Meditation involves sustained focused attention that can be developed by training. Instead of evaluating the meditation practice itself, our approach is to evaluate the neural correlates of performance modulation on an attention paradigm (the Stroop word–color task; SWCT) before and after a meditation retreat. The SWCT relies on the inhibition of reading colored words, a process that tends to dominate and occur earlier than the color recognition process. Color naming can be slowed by the concomitant presence of an incongruent word color. For example, naming ‘blue’ as the color of the word ‘red’ is slower than naming the word ‘blue’ displayed in blue color. In this study we examined the short-term effects of an 8-day long Zen Buddhist meditation retreat (‘Sesshin’) on the performance in the SWCT with fMRI as a feasibility study with a well-known neuropsychological paradigm using a 1.5-T magnet (Signa Twin; Excite V. 10, GE Medical Systems, Milwaukee and EUA, gradient 40 mT/m, and an eight channel head coil). Silicon earplugs and earphones were provided to attenuate acoustic noise. One Zen Buddhist nun and four other regular meditators with at least 6 months of meditation practice were scanned before and after ‘Sesshin’, twice in each session (test–retest design). The subjects gave their written consent, according to the Hospital Israelita Albert Einstein Ethics Committee. The fMRI results of subject C00040 (as a representative of the entire group) shows enhanced activation of the anterior cingulate, right dorsolateral prefrontal, insular, occipital and parietal cortices after meditation practice. According to the literature these areas represent functional activation related to attentional circuitry and reinforce the idea that meditation can further develop attentional abilities that have lasting effects. The small number of subjects does not allow for statistical validation of the results, but the change in each subject compared to the individual’s baseline and the improved performance does encourage us to pursue this experiment design. This new model of investigation is based on studying the effects of meditation while subjects perform neuropsychological paradigms, instead of having them practice meditation within the MR magnet.

Evidence of oesophageal stimulus dependant response in the human anterior cingulate and primary somatosensory cortex

S. J. Coen, L. J. Gregory, L. Yaguez, D. Hall, E. Amaro, S. Smale, S. C. Williams, D. G. Thompson, Q. Aziz Institute of Psychiatry, London, United Kingdom, University of Manchester, Manchester, United Kingdom, Kings College Hospital, London, United Kingdom Synopsis Studies investigating the neural correlates of non-painful and painful oesophageal stimulation have produced variable results. Furthermore, regions involved in the encoding of stimulation intensity are not fully understood. Using a standardised method for establishing quantifiable intensities of oesophageal stimulation, the neural correlates of four levels of oesophageal stimulation were investigated. Stimulation resulted in a complex pattern of cerebral activation that was similar across different levels of stimulation intensity. The anterior cingulate gyrus (ACG) and primary somatosensory cortex (SI), both showed evidence of stimulus dependent response, which may be a result of encoding of intensity and unpleasantness or levels of attention. Introduction Although the functional correlates of non-painful and painful visceral stimulation have previously been investigated (1), the results have been variable. Furthermore, despite the fact that functional Magnetic Resonance Imaging (fMRI) can be used to objectively quantify perception of visceral sensation, regions involved in the encoding of stimulation intensity are not fully understood. By using a standardised method for determining varying intensities of oesophageal stimulation, the neural correlates of four levels of stimulation and the regions involved in encoding of intensity can be investigated. Aims: The purpose of this study was to determine the neural correlates of four intensities of oesophageal stimulation as well as investigating regions involved in the encoding of stimulation intensity, using fMRI. Methods Subjects: 7 healthy volunteers (5 male, mean age 22 years, +7 months) participated in the study. All subjects gave informed, written consent prior to intubation and scanning. The study was approved by our local ethics committee for research. Oesophageal stimulation: a standard manometry catheter with a silicone balloon attached was passed trans-nasally into the lower oesophagus (35cm from the nostril). The catheter was attached to a pump that inflated the balloon with air at regular intervals. The experiment examined four conditions. During each condition one of four balloon distension intensities, obtained by dividing the difference between sensory (the point at which volunteers first perceived a sensation) and pain thresholds (100%) into 4 levels at 25% increments (i.e. 25%, 50%, 75% and 100%), was used to stimulate the distal oesophagus. A modified block design was employed for each intensity, where each “active” and “rest” phase was repeated five times. Behavioural data measuring the subjective perception of the stimulus (0 = non-painful, 5 = discomfort, 10 = extreme pain) was acquired after each active epoch, using visual analogue scales (VAS). fMRI acquisition: Functional Magnetic Resonance Imaging was performed using a GE Neuro-optimised 1.5 Tesla system (General Electric, Milwaukee WI, USA), based at the Maudsley Hospital, London. Sixteen 7mm slices (0.7 mm gap) parallel to the bicomissural plane were acquired, with a repetition time (TR) of 3 seconds and an echo time (TE) of 40ms, flip angle 90o. A total of 122 T2* weighted images per slice, depicting BOLD contrast (Ogawa et al, 1990) were collected over a six minute and six second period of continuous acquisition during which, subjects received localised phasic distensions to the oesophagus. This procedure was performed on four occasions to collect data for four levels of intensity of oesophageal distension. Image Analysis: Spatially realigned BOLD responses were modelled as the weighted sum of the input function convolved with two Poisson functions. A goodness of fit statistic was computed and a voxel-wise inference was carried out non-parametrically. At the group level, individual statistic maps were transformed into standard stereotactic space and median activation images constructed. Results Mean VAS scores increased progressively with increasing stimulation intensities (χ2 = 10.9, df 3, P=0.001), (mean VAS (+SEM); 25% = 3+0.80, 50% = 3.68+0.91, 75% = 5.67+0.79, 100% = 7.34+0.48). 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