Volume 137, Issue 1, Pages 262-273 (July 2009) Mechanisms of Neural Response to Gastrointestinal Nutritive Stimuli: The Gut-Brain Axis  Tomokazu Tsurugizawa, Akira Uematsu, Eiji Nakamura, Mai Hasumura, Mariko Hirota, Takashi Kondoh, Hisayuki Uneyama, Kunio Torii  Gastroenterology  Volume 137, Issue 1, Pages 262-273 (July 2009) DOI: 10.1053/j.gastro.2009.02.057 Copyright © 2009 AGA Institute Terms and Conditions

Figure 1 (A) Three coronal figures from the Paxinos and Watson atlas at +2.0 mm (#1), −0.5 mm (#2), and −3.0 mm (#3) from the bregma. (B) Diagram of fMRI analysis. Functional data are obtained every 15 seconds for 90 minutes. Boxcar function composes “off” period and “on” period. The “off” period is during the 10 minutes before nutrient administration, and the “on” period is for every 5 minutes after the start of administration. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions

Figure 2 (A) Areas of the rat forebrain responding to MSG in intact and TVX rats. T-map images depict the areas with significant increases in BOLD signal intensity. t value shows the significant changes in BOLD signal intensity compared with the preadministration period. (B) Comparisons between intact and TVX rats. t value shows the significant changes in BOLD signal intensity in TVX rats compared with intact rats at the same time period. Color bar, t value. P < .05, corrected. AMG, amygdala; CC, cingulate cortex; CPu, caudate putamen; mPOA, medial preoptic area; DMH, dorsomedial hypothalamus; LH, lateral hypothalamus; HbN, habenular nucleus; HIP, hippocampus; IC, insular cortex; SC, somatosensory cortex; ThN, thalamic nucleus. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions

Figure 3 (A) Areas of rat forebrain in response to glucose in intact and TVX rats. T-map images depict the areas with significant increases in BOLD signal intensity. (B) Comparisons between intact and TVX rats. Positive t value shows the significant increase in BOLD signals in TVX rats compared with intact rats. Color bar, t value. P < .05, corrected. AMG, amygdala; CC, cingulate cortex; CPu, caudate putamen; HIP, hippocampus; IC, insular cortex; SC, somatosensory cortex; ThN, thalamic nucleus; NAC, nucleus accumbens. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions

Figure 4 Changes in (A) blood glucose levels, (B) plasma insulin levels, and (C) plasma GLU levels. Closed circles, MSG in intact rats; closed squares, MSG in TVX rats; open circles, glucose in intact rats; open squares, glucose in TVX rats. *P < .05 compared with other nutrients (MSG or glucose) based on a Tukey–Kramer post-hoc test after analysis of variance in intact rats. †P < .05 compared with TVX rats, based on a Tukey–Kramer post-hoc test after analysis of variance. #P < .05 compared with the preadministration period (0 minutes) based on a paired t test. (D) Gastric emptying at 30 minutes after administration of 60 mmol/L MSG or glucose solution in intact or TVX rats. ***P < .001 compared with intact rats. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions

Figure 5 BOLD responses associated with plasma insulin evoked by postoral glucose in (A) intact and (B) TVX rats (P < .05, corrected). Color bar, t value. Time series data of plasma insulin and BOLD signal intensity in the amygdala and nucleus accumbens in (C and D) intact and (E and F) TVX rats. Data are expressed as means ± SEM. Red lines represent time series data of plasma insulin levels. Black lines represent BOLD signal intensity. *P < .05 compared with the preadministration period. AMG, amygdala; CC, cingulate cortex; CPu, caudate putamen; HIP, hippocampus; IC, insular cortex; SC, somatosensory cortex; ThN, thalamic nucleus; NAC, nucleus accumbens. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions

Figure 6 (A) BOLD responses associated with blood glucose evoked by postoral glucose in intact and TVX rats (P < .05, corrected). Color bar, t value. Time series data of blood glucose and BOLD signal intensity evoked by postoral glucose in the amygdala in (B) intact and (C) TVX rats. (D) BOLD responses associated with plasma GLU evoked by postoral glucose in intact and TVX rats (P < .05, corrected). Time series data of plasma GLU and BOLD signal intensity evoked by postoral MSG in the amygdala in (E) intact and (F) TVX rats. Red lines represent time series data of blood glucose or plasma GLU levels. Black lines represent BOLD signal intensity. Data are expressed as means ± SEM. *P < .05 compared with the preadministration period. Gastroenterology 2009 137, 262-273DOI: (10.1053/j.gastro.2009.02.057) Copyright © 2009 AGA Institute Terms and Conditions