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Pain Cortical Processing in Symptomatic Diverticular Disease: A Functional Magnetic Resonance Imaging Study
AGA Abstracts
HCl infusion d) post-infusion. Data was preprocessed according to standard published methods. Deglutition network seed regions were identified in a separate paradigm driven functional scan when volunteers were visually cued to swallow at random times. Cross correlation coefficient values were computed between study conditions to evaluate connectivity. Results: Within the deglutition network, bilateral motor associated areas (premotor cortex, sensorimotor strip, rolandic operculum) and bilateral anterior insula with ventrolateral prefrontal cortex were highly correlated within all study conditions. Between study conditions, subtle differences were noted in the degree of correlation between seed region pairs. A dimensionally reduced, single-parameter model of the deglutition network revealed that the functional connectivity was significantly altered during esophageal acid perfusion compared to the pre-infusion period (p<0.03) but not during buffer infusion compared to the pre-infusion period (p=0.80) (Figure). Conclusion: Esophageal acid stimulation modifies the functional connectivity of the deglutition network in healthy individuals. These modifications are manifested by variations in the degree of correlation between components of the deglutition network.
nausea which is potentially an animal welfare issue. Thus we aimed to study the psychophysiological & brain processing response to a novel human model of nausea. Methods:A 10minute video that induced motion sickness & another that did not (control video) were presented to 51 healthy volunteers (age 27 ± 8 years, 22 male) with tests of nausea & personality questionnaires; cardiac sympathetic (cardiac sympathetic index CSI, heart rate HR, mean blood pressure MBP) & parasympathetic (cardiac vagal tone CVT, cardiac sensitivity to baroreceptor reflex CSB) measures. In addition, cortisol levels & electrogastrogram (EGG) were measured. Subsequently, 9 susceptible subjects had the same stimuli again (age 25 ± 5 years, 5 male) with functional MRI that was analysed with XBAM. Results:All subjects completed the studies without vomiting. When comparing nausea video (NV) to control, NV raised nausea scores (nausea VAS,+57%±11,p<0.01). NV also raised cardiac sympathetic activity (HR +4.04 ± 0.94,p<0.01; SBP +2.4 ± 1.75,p=0.18; DBP +2.23±0.98,p<0.05; MBP +2.28±1.12,p<0.05) & reduced parasympathetic activity (CVT -1.36 ± 0.49 ,p<0.01; CSB -1.27 ± 0.61,p<0.05); & raised dominant frequency on EGG (3.0±0.04 vs 2.8±0.05, p<0.02). When comparing nausea susceptible vs resistant subjects, subjects with moderate to severe nausea lowered CVT & CSB; raised HR; raised cortisol; & reduced dominant power on EGG (% change from baseline -20.6±7.7 vs -11.2±0.8,p<0.01; -25.1±9.4 vs 8.2±10.7,p<0.05; 10.4±3.4 vs 0.8±2.2,p<0.05; 16.9±20.2 vs -28.5±4.9,p<0.05; -2.81±1.36 vs -0.17±0.93,p<0.01 respectively). The 9 susceptible subjects (fMRI) when comparing NV to control showed correlations to nausea levels with an increase in brain activity in the inferior frontal gyrus (p<0.01) & temporal lobe (p<0.01) & a decrease in brain activity in multiple areas of the occipital lobe (p<0.01) & cerebellum (p<0.05). Conclusion:This model is safe & effective. Nausea susceptible subjects reduced CVT & CSB; raised HR; raised cortisol; & reduced dominant power on EGG from baseline compared to resistant subjects. They also show different brain processing patterns in the NV compared to control video. As motion sickness is known to induce gastrointestinal (GI) physiological changes, this model may be used to study the effects of nausea on GI function in health & disease together with the option of correlating these changes to objective physiological & brain processing biomarkers. These biomarkers can then be used for reverse translation in animals to potentially improve animal models as well as reduce animal suffering from undetected nausea. Sa2012 Reproducibility of the Resting and Active State Connectivity of the Deglutition Connectome Arash Babaei, B. Douglas Ward, Wenjun Li, Shi-Jiang Li, Reza Shaker Background & Aim: Coherent and synchronized spontaneous resting state fluctuation of blood oxygenation level dependent (BOLD) signal has emerged as a new important technique to study underlying neuronal networks of human brain. This connectivity is modified in different physiologic and pathologic conditions. Earlier studies have described resting and active connectivity of the swallow network. However, reproducibility of this finding has not been shown. Our aim was to systematically evaluate the reproducibility of the “deglutition connectome” Methods: 16 young right-handed healthy volunteers underwent 6 studies across two different sessions within the same day. Resting and active data were obtained for 540 seconds in three conditions: a) awake rest state with closed eyes without any cognitive or behavioral task b) swallow state dry swallows triggered by randomly spaced visual cues and c) resting state with eyes open processing randomly spaced null visual commands in the same intervals as condition b and then repeated. Data was preprocessed according to standard methods and prior published data. Activated seed regions within known areas of the swallowing network were identified via an independently obtained seventh functional run during which subjects randomly swallowed using a paradigm driven protocol and analyzed by means of event-related technique. We determined the correlation co-efficient values of “deglutition connectome” across three aforementioned conditions and compared between two sessions using linear regression at individual and group level. Results: Deglutition connectome included eighteen positive BOLD and sixteen negative BOLD activated bihemispheric seed regions. 1) Positive BOLD seed regions are highly connected as negative BOLD regions are tightly connected amongst themselves 2) Cross connectivity of positive and negative BOLD activated regions is very low 3) At both individual and group level and across all three conditions: resting eyes closed (r=0.69, p<10-6, n=15), resting eyes open (r=0.74, p<10-6, n=15, shown in figure) and swallow (r=0.74, p<10-6, n=12), the deglutition connectome is remarkably resilient and constant. Conclusions: 1) Deglutition connectome is consistent and reproducible across different study conditions and sessions. 2) This connectome represented by s trong and significant connectivity of the positive and negative swallow-associated BOLD activated seeds further supports the existence of a swallow specific cortical network.
Sa2010 Pain Cortical Processing in Symptomatic Diverticular Disease: A Functional Magnetic Resonance Imaging Study Jan Smith, David J. Humes, Kay E. Head, John Scholefield, Luca Marciani, Susan Francis, Penny A. Gowland, Robin C. Spiller Background: 30% of patients with diverticular disease (DD) suffer recurrent episodes of short lived abdominal pain [1]. Symptomatic DD patients demonstrate visceral hypersensitivity on barostat examination. Visceral hypersensitivity is not well understood in DD and can be caused by (a) altered peripheral nerves (b) hyper-excitability of ascending spinal nerves or (c) dysregulation of descending inhibitory fibres [2]. Alteration in cutaneous sensitivities in regions sharing viscerosomatic convergence with the effected organ, have been demonstrated in other painful gastrointestinal conditions [3,4]. However, brain imaging assessment of pain pathways in DD has not previously been undertaken. Aims: To assess functional magnetic resonance imaging (fMRI) of thermal pain delivered to the dorsal surface of the left foot and hand using a Peltier thermode in a group of symptomatic DD patients. Methods: 12 right-handed (7 female, median age 60yrs, range 41-67yrs), symptomatic DD patients underwent sensitivity testing using a Medoc Peltier device and visual analogue scales to determine their individual pain threshold to thermal stimulation of the back of the left foot and hand. fMRI was carried out using two pseudo-randomized paradigms delivering painful stimuli in a 3T MRI scanner. fMRI statistical parametric mapping was performed in SPM8 with data sets processed individually to evaluate activation patterns to the painful stimuli. A random effects (RFX) group analysis was then performed, corrected for family-wise error (P < 0.05). Results: The mean individual temperature used for painful stimulation was (mean±SD) 46±1 oC for both the hand and the foot painful stimulation while mean corresponding VAS pain scores were 6.3±2.2 and 6.3±2.3 respectively (with 0 being no pain and 10 being severe pain). Random effects group data showed significant activation in several cortical areas including bilateral anterior insula, bilateral mid-insula, anterior cingulate cortex and right somatosensory cortex for both foot and hand areas. Conclusion: The brain areas activated by thermal painful stimulation were in good agreement with the expected cortical response to pain [5]. The fMRI assessment of cortical activation to painful stimuli in symptomatic DD patients is novel. Such data will allow us to determine differences in cortical and sub-cortical pain processing between symptomatic DD and contrasting diseases such as asymptomatic DD and IBS. This will ultimately improve understanding of dysfunction of peripheral or central pain mechanism in DD. References: [1] Humes DJ et al. Br J Surg 2008;95:195-198. [2] Azpiroz F et al NGM 2007; 19,S1 :62-88. [3] Hobson AR et al. Am J Physiol 298:G31-36. [4] Kurucsai G et al. Am J Gastroenterol 2008;103:2717-2725. [5] Peyron R et al. Neurophysiol Clin 2000;30:263-288.
Sa2013 The Effect of Cognitive Load on Interoceptive Processing Jennifer S. Labus, Bahar Ebrat, Zhiguo Jiang, Jean Stains, Kirsten Tillisch, Bruce D. Naliboff, Emeran A. Mayer While in healthy subjects,the majority of interoceptive signals are not consciously perceived, irritable bowel syndrome patients show increased perception of such signals from the gut. It is unknown if this is due to increased afferent signaling from the gut(encoded in the posterior insula[pINS],the primary interoceptive cortex) or due to central amplification of the signal in the anterior INS;encoding intensity)and the anterior midcingulate cortex(aMCC; encoding unpleasantness by attentional processes. Aims:Determine in healthy participants 1) if pINS is activated by subliminal and mildly supraliminal visceral distension, when attention is focused not on the gut, but on a cognitive task 2) if low level gut distension affects cognitive performance. Methods:Ten healthy subjects(5 F;m=29 y) with moderate levels of state(m=43) and trait(m=39)anxiety participated. Brain activity was measured with a Siemens Allegra 3T MRI scanner while subjects performed a validated, high or a low cognitive processing(letter search) task during 20s blocks of subliminal(10mmHg)or supraliminal(20mmHg)rectal distension, as well as during baseline pressure of 5mmHg. Subjects were told 1) to focus exclusively on the cognitive task, and 2) not pay any attention to possible subtle variations in balloon pressure. Effects of gut distension on the cognitive task were examined by contrasting brain activity during distension(10 or 20mmHg) versus the
Sa2011 Identifying Human Biomarkers of Nausea for Refining Animal Studies on Emesis Kee S. Ng, Yang C. Chua, Vin Fei Ban, Michael Gresty, Steven J. Coen, Gareth J. Sanger, Steven C. Williams, Gareth Barker, Paul Andrews, Qasim Aziz Nausea is a common & complex multi-system subjective symptom. There is a lack of objective biomarkers to assess nausea & nausea susceptibility in humans which makes clinical decisions difficult. Furthermore, animal studies have no agreed criteria to identify
AGA Abstracts
S-368
HCl infusion d) post-infusion. Data was preprocessed according to standard published methods. Deglutition network seed regions were identified in a separate paradigm driven functional scan when volunteers were visually cued to swallow at random times. Cross correlation coefficient values were computed between study conditions to evaluate connectivity. Results: Within the deglutition network, bilateral motor associated areas (premotor cortex, sensorimotor strip, rolandic operculum) and bilateral anterior insula with ventrolateral prefrontal cortex were highly correlated within all study conditions. Between study conditions, subtle differences were noted in the degree of correlation between seed region pairs. A dimensionally reduced, single-parameter model of the deglutition network revealed that the functional connectivity was significantly altered during esophageal acid perfusion compared to the pre-infusion period (p<0.03) but not during buffer infusion compared to the pre-infusion period (p=0.80) (Figure). Conclusion: Esophageal acid stimulation modifies the functional connectivity of the deglutition network in healthy individuals. These modifications are manifested by variations in the degree of correlation between components of the deglutition network.
nausea which is potentially an animal welfare issue. Thus we aimed to study the psychophysiological & brain processing response to a novel human model of nausea. Methods:A 10minute video that induced motion sickness & another that did not (control video) were presented to 51 healthy volunteers (age 27 ± 8 years, 22 male) with tests of nausea & personality questionnaires; cardiac sympathetic (cardiac sympathetic index CSI, heart rate HR, mean blood pressure MBP) & parasympathetic (cardiac vagal tone CVT, cardiac sensitivity to baroreceptor reflex CSB) measures. In addition, cortisol levels & electrogastrogram (EGG) were measured. Subsequently, 9 susceptible subjects had the same stimuli again (age 25 ± 5 years, 5 male) with functional MRI that was analysed with XBAM. Results:All subjects completed the studies without vomiting. When comparing nausea video (NV) to control, NV raised nausea scores (nausea VAS,+57%±11,p<0.01). NV also raised cardiac sympathetic activity (HR +4.04 ± 0.94,p<0.01; SBP +2.4 ± 1.75,p=0.18; DBP +2.23±0.98,p<0.05; MBP +2.28±1.12,p<0.05) & reduced parasympathetic activity (CVT -1.36 ± 0.49 ,p<0.01; CSB -1.27 ± 0.61,p<0.05); & raised dominant frequency on EGG (3.0±0.04 vs 2.8±0.05, p<0.02). When comparing nausea susceptible vs resistant subjects, subjects with moderate to severe nausea lowered CVT & CSB; raised HR; raised cortisol; & reduced dominant power on EGG (% change from baseline -20.6±7.7 vs -11.2±0.8,p<0.01; -25.1±9.4 vs 8.2±10.7,p<0.05; 10.4±3.4 vs 0.8±2.2,p<0.05; 16.9±20.2 vs -28.5±4.9,p<0.05; -2.81±1.36 vs -0.17±0.93,p<0.01 respectively). The 9 susceptible subjects (fMRI) when comparing NV to control showed correlations to nausea levels with an increase in brain activity in the inferior frontal gyrus (p<0.01) & temporal lobe (p<0.01) & a decrease in brain activity in multiple areas of the occipital lobe (p<0.01) & cerebellum (p<0.05). Conclusion:This model is safe & effective. Nausea susceptible subjects reduced CVT & CSB; raised HR; raised cortisol; & reduced dominant power on EGG from baseline compared to resistant subjects. They also show different brain processing patterns in the NV compared to control video. As motion sickness is known to induce gastrointestinal (GI) physiological changes, this model may be used to study the effects of nausea on GI function in health & disease together with the option of correlating these changes to objective physiological & brain processing biomarkers. These biomarkers can then be used for reverse translation in animals to potentially improve animal models as well as reduce animal suffering from undetected nausea. Sa2012 Reproducibility of the Resting and Active State Connectivity of the Deglutition Connectome Arash Babaei, B. Douglas Ward, Wenjun Li, Shi-Jiang Li, Reza Shaker Background & Aim: Coherent and synchronized spontaneous resting state fluctuation of blood oxygenation level dependent (BOLD) signal has emerged as a new important technique to study underlying neuronal networks of human brain. This connectivity is modified in different physiologic and pathologic conditions. Earlier studies have described resting and active connectivity of the swallow network. However, reproducibility of this finding has not been shown. Our aim was to systematically evaluate the reproducibility of the “deglutition connectome” Methods: 16 young right-handed healthy volunteers underwent 6 studies across two different sessions within the same day. Resting and active data were obtained for 540 seconds in three conditions: a) awake rest state with closed eyes without any cognitive or behavioral task b) swallow state dry swallows triggered by randomly spaced visual cues and c) resting state with eyes open processing randomly spaced null visual commands in the same intervals as condition b and then repeated. Data was preprocessed according to standard methods and prior published data. Activated seed regions within known areas of the swallowing network were identified via an independently obtained seventh functional run during which subjects randomly swallowed using a paradigm driven protocol and analyzed by means of event-related technique. We determined the correlation co-efficient values of “deglutition connectome” across three aforementioned conditions and compared between two sessions using linear regression at individual and group level. Results: Deglutition connectome included eighteen positive BOLD and sixteen negative BOLD activated bihemispheric seed regions. 1) Positive BOLD seed regions are highly connected as negative BOLD regions are tightly connected amongst themselves 2) Cross connectivity of positive and negative BOLD activated regions is very low 3) At both individual and group level and across all three conditions: resting eyes closed (r=0.69, p<10-6, n=15), resting eyes open (r=0.74, p<10-6, n=15, shown in figure) and swallow (r=0.74, p<10-6, n=12), the deglutition connectome is remarkably resilient and constant. Conclusions: 1) Deglutition connectome is consistent and reproducible across different study conditions and sessions. 2) This connectome represented by s trong and significant connectivity of the positive and negative swallow-associated BOLD activated seeds further supports the existence of a swallow specific cortical network.
Sa2010 Pain Cortical Processing in Symptomatic Diverticular Disease: A Functional Magnetic Resonance Imaging Study Jan Smith, David J. Humes, Kay E. Head, John Scholefield, Luca Marciani, Susan Francis, Penny A. Gowland, Robin C. Spiller Background: 30% of patients with diverticular disease (DD) suffer recurrent episodes of short lived abdominal pain [1]. Symptomatic DD patients demonstrate visceral hypersensitivity on barostat examination. Visceral hypersensitivity is not well understood in DD and can be caused by (a) altered peripheral nerves (b) hyper-excitability of ascending spinal nerves or (c) dysregulation of descending inhibitory fibres [2]. Alteration in cutaneous sensitivities in regions sharing viscerosomatic convergence with the effected organ, have been demonstrated in other painful gastrointestinal conditions [3,4]. However, brain imaging assessment of pain pathways in DD has not previously been undertaken. Aims: To assess functional magnetic resonance imaging (fMRI) of thermal pain delivered to the dorsal surface of the left foot and hand using a Peltier thermode in a group of symptomatic DD patients. Methods: 12 right-handed (7 female, median age 60yrs, range 41-67yrs), symptomatic DD patients underwent sensitivity testing using a Medoc Peltier device and visual analogue scales to determine their individual pain threshold to thermal stimulation of the back of the left foot and hand. fMRI was carried out using two pseudo-randomized paradigms delivering painful stimuli in a 3T MRI scanner. fMRI statistical parametric mapping was performed in SPM8 with data sets processed individually to evaluate activation patterns to the painful stimuli. A random effects (RFX) group analysis was then performed, corrected for family-wise error (P < 0.05). Results: The mean individual temperature used for painful stimulation was (mean±SD) 46±1 oC for both the hand and the foot painful stimulation while mean corresponding VAS pain scores were 6.3±2.2 and 6.3±2.3 respectively (with 0 being no pain and 10 being severe pain). Random effects group data showed significant activation in several cortical areas including bilateral anterior insula, bilateral mid-insula, anterior cingulate cortex and right somatosensory cortex for both foot and hand areas. Conclusion: The brain areas activated by thermal painful stimulation were in good agreement with the expected cortical response to pain [5]. The fMRI assessment of cortical activation to painful stimuli in symptomatic DD patients is novel. Such data will allow us to determine differences in cortical and sub-cortical pain processing between symptomatic DD and contrasting diseases such as asymptomatic DD and IBS. This will ultimately improve understanding of dysfunction of peripheral or central pain mechanism in DD. References: [1] Humes DJ et al. Br J Surg 2008;95:195-198. [2] Azpiroz F et al NGM 2007; 19,S1 :62-88. [3] Hobson AR et al. Am J Physiol 298:G31-36. [4] Kurucsai G et al. Am J Gastroenterol 2008;103:2717-2725. [5] Peyron R et al. Neurophysiol Clin 2000;30:263-288.
Sa2013 The Effect of Cognitive Load on Interoceptive Processing Jennifer S. Labus, Bahar Ebrat, Zhiguo Jiang, Jean Stains, Kirsten Tillisch, Bruce D. Naliboff, Emeran A. Mayer While in healthy subjects,the majority of interoceptive signals are not consciously perceived, irritable bowel syndrome patients show increased perception of such signals from the gut. It is unknown if this is due to increased afferent signaling from the gut(encoded in the posterior insula[pINS],the primary interoceptive cortex) or due to central amplification of the signal in the anterior INS;encoding intensity)and the anterior midcingulate cortex(aMCC; encoding unpleasantness by attentional processes. Aims:Determine in healthy participants 1) if pINS is activated by subliminal and mildly supraliminal visceral distension, when attention is focused not on the gut, but on a cognitive task 2) if low level gut distension affects cognitive performance. Methods:Ten healthy subjects(5 F;m=29 y) with moderate levels of state(m=43) and trait(m=39)anxiety participated. Brain activity was measured with a Siemens Allegra 3T MRI scanner while subjects performed a validated, high or a low cognitive processing(letter search) task during 20s blocks of subliminal(10mmHg)or supraliminal(20mmHg)rectal distension, as well as during baseline pressure of 5mmHg. Subjects were told 1) to focus exclusively on the cognitive task, and 2) not pay any attention to possible subtle variations in balloon pressure. Effects of gut distension on the cognitive task were examined by contrasting brain activity during distension(10 or 20mmHg) versus the
Sa2011 Identifying Human Biomarkers of Nausea for Refining Animal Studies on Emesis Kee S. Ng, Yang C. Chua, Vin Fei Ban, Michael Gresty, Steven J. Coen, Gareth J. Sanger, Steven C. Williams, Gareth Barker, Paul Andrews, Qasim Aziz Nausea is a common & complex multi-system subjective symptom. There is a lack of objective biomarkers to assess nausea & nausea susceptibility in humans which makes clinical decisions difficult. Furthermore, animal studies have no agreed criteria to identify
AGA Abstracts
S-368