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

Abstract

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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