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Control centers in the central nervous system for regulating gastrointestinal motility

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Abstract

The sections in this article are:

1 Identification with Retrograde Neuronal Tracing Techniques of CNS Centers Influencing GI Motility
1.1 Parasympathetic Neural Pathways
1.2 Sympathetic Neural Pathways
1.3 Sensory Neural Pathways
2 Stimulation of CNS Centers Identified by Retrograde Neuronal Tracing Techniques
2.1 Parasympathetic Centers
2.2 Sympathetic Centers
2.3 Centers Defined by Tracing Afferent Pathways
3 Neuroanatomical Description of CNS Centers Influencing GI Motility
3.1 Parasympathetic Centers
3.2 Sympathetic Centers
3.3 Sensory Centers
4 Neuronal Inputs and Outputs of CNS Centers Influencing GI Motility
4.1 Parasympathetic Centers
4.2 Sympathetic Centers
4.3 Sensory Centers
5 Stimulation and Lesion of CNS Nuclei Projecting to CNS Sites Influencing GI Motility
5.1 Cerebral Cortex
5.2 Amygdala and Bed Nucleus of Stria Terminalis
5.3 Paraventricular Nucleus of the Hypothalamus
5.4 Nucleus Tractus Solitarius
5.5 Medullary Reticular Nuclei
5.6 Parabrachial Nucleus
5.7 Inputs to the Spinal Cord
5.8 Other Sites
6 Overview of Brain‐Gut Neural Circuitry
7 Role of Brain‐Gut Neural Circuitry in Regulation of GI Motility
7.1 Role of Cerebral Cortex to Nucleus Tractus Solitarius Pathway
7.2 Role of Pathway from Periventricular area of the Hypothalamus to the Dorsal Motor Nucleus of the Vagus
7.3 Role of Cerebral Cortex to Onuf's Nucleus Pathway
7.4 Role of Spinal Reflex Involving Afferent Fibers in the Pudendal Nerve and Onuf's Nucleus and Efferent Fibers in the Pudendal Nerve
7.5 Role of Sympathetic Centers in the Spinal Cord
7.6 Role of Retrofacial Nucleus, Nucleus Ambiguus, and Dorsal Motor Nucleus of Vagus Pathways to Upper and Lower Esophageal Sphincters
7.7 Role of Afferent Fibers in Vagus Nerve, Nucleus Tractus Solitarius, and Neurons in Dorsal Motor Nucleus of the Vagus in Receptive Relaxation
8 Concepts Emerging from Studies of Control Centers
Figure 1. Figure 1.

Diagram of nuclei of central nervous system (CNS; parasympathetic) that innervate various regions of the gastrointestinal (GI) tract from upper esophageal sphincter (UES) to external anal sphincter (EAS). A/P, antrum/pylorus; Ca, cardial; CE, cervical esophagus; Co, corpus of stomach; D, duodenum; DC, distal colon; DMV, dorsal motor nucleus of vagus; F, fundus of stomach; I, ileum; IML, intermediolateral cell column; J, jejunum; LES, lower esophageal sphincter; MC, midcolon; NA, nucleus ambiguus; NRA, nucleus retroambiguus; O, obex; ON, Onuf's nucleus; PC, proximal colon; R, rectum; RF, retrofacial nucleus; S1–3, sacral spinal cord segments 1 to 3; TE, thoracic esophagus; 7, facial nucleus.

Figure 2. Figure 2.

Diagram of medial and lateral columns of neurons within dorsal motor nucleus of vagus 10 that give rise to axons that travel through the gastric branch of the vagus to various parts of the stomach. Gastric nerves proper innervate the fundus and corpus, whereas the nerve of Laterjet passes to the antrum‐pylorus region of the stomach. IO, inferior olivary nucleus; NTS, nucleus tractus solitarius; SpTr V, spinal tract of trigeminal nerve; XII, hypoglossal nucleus. Black dots within nucleus X, many neurons within a rostrocaudal column of cells.

Figure 3. Figure 3.

Source of sympathetic innervation to GI tract. CG, celiac ganglion; EAS, innervation to external anal sphincter; IMG, inferior mesenteric ganglion; SCG, superior cervical ganglion; SG, stellate ganglion; SMG, superior mesenteric ganglion; T1, 1st thoracic spinal cord segment; T6, 6th thoracic spinal cord segment.

Figure 4. Figure 4.

Pathway taken by vagal afferent fibers from GI tract to tractus solitarius (TS). Stippled area medial to tractus solitarius, one of nuclei of the tractus, the medial nucleus. Arrows, flow of impulses from GI tract. 10, inferior olivary nucleus; mnTS, medial nucleus tractus solitarius; NA, nucleus ambiguus; SpTr 5, spinal tract of trigeminal nerve; 10, dorsal motor nucleus of vagus; 12, hypoglossal nucleus.

Figure 5. Figure 5.

A: subnuclear groups of tractus solitarius at a level 0.4 mm rostral to the obex. B: commissural nucleus at a level 0.85 mm caudal to the obex, ap, Area postrema; CC, central canal; dlnTS, dorsolateral nucleus of tractus solitarius; dnTS, dorsal nTS; g, nucleus gracilis; mnTS, medial nTS; ncom, commissural nTS; ni, intermediate nTS; ni, interstitial nTS; sg, subgelatinous nTS; TS, tractus solitarius; vlnTS, ventrolateral nTS; vnTS, ventral nTS; 10, dorsal motor nucleus of vagus; 12, hypoglossal nucleus.

Adapted from Kalia and Mesulam 147
Figure 6. Figure 6.

Pelvic afferent neurons and their termination within spinal cord segments that extend from 4th lumbar segment to as far caudal as 1st coccygeal segment. Only sacral segments 1–3 are demonstrated, cc, Central canal; CX1, 1st coccygeal segment; DB, dorsal band of parasympathetic neurons; DCL, dorsal column; DH, dorsal horn; DRG, dorsal root ganglion; LB, lateral band of parasympathetic neurons; LCP, lateral collateral pathway; LF, lateral funiculus; L4‐L7, 4th through 7th lumbar segments of spinal cord; LT, Lissauer's tract; MCP, medial collateral pathway; VH, ventral horn. Asterisks, groups of neuron cell bodies of either parasympathetic preganglionic neurons or somatic motoneurons.

Figure 7. Figure 7.

Pathway taken by sympathetic afferent neurons from GI tract to CNS, primarily in midlumbar segments of spinal cord, cc, Central canal; DH, dorsal horn; DR, dorsal root; DRG, dorsal root ganglion; LCP, lateral collateral pathway; LS, lumbar splanchnic nerve; LT, Lissauer's tract; L3, L4, L5, lumbar spinal cord segments 3–5; MCP, medial collateral pathway; SG, sympathetic chain ganglion; VH, ventral horn; VR, ventral root. Asterisks, groups of preganglionic sympathetic neurons.

From Barone et al. 22
Figure 8. Figure 8.

Pudendal afferent neurons that arise primarily from area of external anal sphincter. Neurons travel by way of pudendal nerves into lower lumber (L7) segments 1–3 of sacral spinal cord. Afferents enter Lissauer's tract (LT) and give rise to medial and lateral collateral pathways (LCP) that terminate near the dorsal band (DB) of preganglionic neurons. Other afferents pass upward through dorsal funiculus to reach nucleus gracilis in the brain stem. DH, dorsal horn; DRG, dorsal root ganglion; VH, ventral horn.

Figure 9. Figure 9.

Distribution of fast blue‐labeled neurons in right (upper) and left (lower) dorsal motor nucleus of vagus (DMV) after fast blue injections into antrum and pylorus. Vertical axis, number of labeled cell bodies in DMV per 0.14 mm (sum of 5 serial 28‐μm sections). Horizontal axis, location in DMV (relative to obex in mm) of number of cell bodies.

From Pagani et al. 245
Figure 10. Figure 10.

Effect of electrical Stimulation (100 μA, 50 Hz, 0.2‐ms pulse duration) of dorsal motor nucleus of vagus on gastric motility and cardiovascular function. Arrow, stimulus was turned on. Small change in heart rate (HR).

From Pagani et al. 245
Figure 11. Figure 11.

Coronal section of brain stem passing through dorsal motor nucleus of vagus. Lesion site lies confined to dorsal medial aspect of dorsal motor nucleus of vagus (X). Electrical stimulation at that site produced the increase in contractile activity observed in Figure 10. mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.

From Pagani et al. 245
Figure 12. Figure 12.

Effect of electrical stimulation of 4 specific regions of dorsal motor nucleus of vagus on minute motility index (MMI). Cross‐hatched bars, changes in MMI of antrum; solid bars, changes in MMI of pylorus. Vertical bars, standard error of the mean. Data from each histogram were derived from 4–6 animals. Small asterisks, response was statistically significant (P < 0.05) from control using paired t test. Large asterisks, response was significantly (P < 0.05) attenuated compared with maximal response occurring from 1.5 to 2.0 mm rostral to obex using t test for grouped data.

From Pagani et al. 245
Figure 13. Figure 13.

Comparison of changes in minute motility index (MMI) induced by electrical stimulation of dorsal motor nucleus of vagus (DMV; left) and of brain sites medial to DMV (right). Cross‐hatched bars, changes in MMI of antrum; solid bars, changes in MMI of pylorus. Vertical bars, standard error of the mean. Data for each histogram were derived from 5–10 animals.

Adapted from Pagani et al. 245
Figure 14. Figure 14.

Coronal section of brain stem passing through dorsal motor nucleus of vagus (DMV). Lesion site lies medial to DMV (X). mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.

From Pagani et al. 245
Figure 15. Figure 15.

Experiment showing effect of microinjection of L‐glutamic acid (arrow) into dorsal motor nucleus of vagus on gastric motility and cardiovascular function.

From Gillis et al. 90
Figure 16. Figure 16.

Coronal section of brain stem passing through dorsal motor nucleus of vagus (DMV). Microinjection site lies in DMV X. mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.

Figure 17. Figure 17.

Cross section of brainstem, 2.3 mm rostral to obex, that shows relationship of neuronal axons from nucleus ambiguus (NA) to dorsal motor nucleus of vagus (DMV) as they exit the brain stem. 10, inferior olivary nucleus; SpTr V, spinal tract of trigeminal nerve; TS, tractus solitarius; XII, hypoglossal nucleus.

Figure 18. Figure 18.

Effect of electrical stimulation (133 μA, 50 Hz, 0.2‐ms pulse duration) of nucleus ambiguus complex on gastric secretion (gastric pH, microe‐quivalents of H+, and peptic units), gastroduodenal motility, arterial pressure, and heart rate (HR). Left panels: control traces and values. Right panels: traces obtained immediately after electrical stimulation was initiated (arrows). Values for pH, microequivalents of H+, and peptic units are values obtained either over a 10‐min control collective period (left) or over a 10‐min period of electrical stimulation on nucleus ambiguus complex (right). MMI, minute motility index.

From Pagani et al. 244
Figure 19. Figure 19.

Coronal section of brain stem passing through nucleus ambiguus (arrow), tractus solitarius (TS), dorsal motor nucleus of vagus (X), hypoglossal nucleus (XII), and inferior olivary nucleus (IO).

Adapted from Pagani et al. 244
Figure 20. Figure 20.

Thoracolumbar portion of the spinal cord showing intermediate gray matter and its subnuclear groups, connection of upper thoracic segments of spinal cord to cervical ganglia of sympathetic chain, and connection of lumbar segments of spinal cord to lumbar part of the sympathetic chain. CA, central autonomic neurons; CC, central canal; IC, spinal intercalated nucleus; IMLf, funicular part of intermediolateral cell column; IMLp, principal part of intermediolateral cell column.

Figure 21. Figure 21.

Diagram of CNS demonstrating pathways that interconnect different nuclei that are involved in control of the GI system. A: overall wiring diagram. B: enlargement of medullary segment to show interconnections of dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA), nucleus tractus solitarius (NTS), medullary reticular formation (MRF), ventrolateral medulla (VLM), and raphe obscurus (RO). ACh, acetylcholine; NC, nucleus cuneatus; ON, Onuf's nucleus; SpTr V, spinal tract of trigeminal nerve.

Figure 22. Figure 22.

Proposed scheme of CNS neural pathways activated by blockade of effects of GABA in periventricular nucleus of the hypothalamus, resulting in increases in gastric motility and antagonism of vagal effects on the heart. We propose that blockade of GABAergic transmission occurs at interneurons located in the hypothalamus and results in activation of neurons projecting to GABA‐inhibitory interneurons located in the region of nucleus ambiguus (NA), as well as activation of a collateral branch of the same neuron that projects to excitatory interneurons in the dorsal motor nucleus of vagus (DMV). End result is an increase in parasympathetic outflow to the stomach and a decrease in parasympathetic outflow to the heart.

Adapted from Pagani et al. 243
Figure 23. Figure 23.

Proposed scheme showing how blockade of sympathetic nervous system activity to the colon can result in colonic contractions. Presumably enteric ganglia cells are active and are responsible for tonic release of acetylcholine (ACh) at smooth muscle of colon. In addition, tonic sympathetic activity originating from the spinal cord results in release of norepinephrine (NE) at enteric ganglia. Released NE acts on α2‐adrenergic receptors located on enteric ganglia cells to cause hyperpolarization and inhibit release of ACh. Blockade of α2‐adrenergic receptors removes this inhibitory noradrenergic input and results in cholinergically mediated increases in colonic motility. IML, intermediolateral cell column.



Figure 1.

Diagram of nuclei of central nervous system (CNS; parasympathetic) that innervate various regions of the gastrointestinal (GI) tract from upper esophageal sphincter (UES) to external anal sphincter (EAS). A/P, antrum/pylorus; Ca, cardial; CE, cervical esophagus; Co, corpus of stomach; D, duodenum; DC, distal colon; DMV, dorsal motor nucleus of vagus; F, fundus of stomach; I, ileum; IML, intermediolateral cell column; J, jejunum; LES, lower esophageal sphincter; MC, midcolon; NA, nucleus ambiguus; NRA, nucleus retroambiguus; O, obex; ON, Onuf's nucleus; PC, proximal colon; R, rectum; RF, retrofacial nucleus; S1–3, sacral spinal cord segments 1 to 3; TE, thoracic esophagus; 7, facial nucleus.



Figure 2.

Diagram of medial and lateral columns of neurons within dorsal motor nucleus of vagus 10 that give rise to axons that travel through the gastric branch of the vagus to various parts of the stomach. Gastric nerves proper innervate the fundus and corpus, whereas the nerve of Laterjet passes to the antrum‐pylorus region of the stomach. IO, inferior olivary nucleus; NTS, nucleus tractus solitarius; SpTr V, spinal tract of trigeminal nerve; XII, hypoglossal nucleus. Black dots within nucleus X, many neurons within a rostrocaudal column of cells.



Figure 3.

Source of sympathetic innervation to GI tract. CG, celiac ganglion; EAS, innervation to external anal sphincter; IMG, inferior mesenteric ganglion; SCG, superior cervical ganglion; SG, stellate ganglion; SMG, superior mesenteric ganglion; T1, 1st thoracic spinal cord segment; T6, 6th thoracic spinal cord segment.



Figure 4.

Pathway taken by vagal afferent fibers from GI tract to tractus solitarius (TS). Stippled area medial to tractus solitarius, one of nuclei of the tractus, the medial nucleus. Arrows, flow of impulses from GI tract. 10, inferior olivary nucleus; mnTS, medial nucleus tractus solitarius; NA, nucleus ambiguus; SpTr 5, spinal tract of trigeminal nerve; 10, dorsal motor nucleus of vagus; 12, hypoglossal nucleus.



Figure 5.

A: subnuclear groups of tractus solitarius at a level 0.4 mm rostral to the obex. B: commissural nucleus at a level 0.85 mm caudal to the obex, ap, Area postrema; CC, central canal; dlnTS, dorsolateral nucleus of tractus solitarius; dnTS, dorsal nTS; g, nucleus gracilis; mnTS, medial nTS; ncom, commissural nTS; ni, intermediate nTS; ni, interstitial nTS; sg, subgelatinous nTS; TS, tractus solitarius; vlnTS, ventrolateral nTS; vnTS, ventral nTS; 10, dorsal motor nucleus of vagus; 12, hypoglossal nucleus.

Adapted from Kalia and Mesulam 147


Figure 6.

Pelvic afferent neurons and their termination within spinal cord segments that extend from 4th lumbar segment to as far caudal as 1st coccygeal segment. Only sacral segments 1–3 are demonstrated, cc, Central canal; CX1, 1st coccygeal segment; DB, dorsal band of parasympathetic neurons; DCL, dorsal column; DH, dorsal horn; DRG, dorsal root ganglion; LB, lateral band of parasympathetic neurons; LCP, lateral collateral pathway; LF, lateral funiculus; L4‐L7, 4th through 7th lumbar segments of spinal cord; LT, Lissauer's tract; MCP, medial collateral pathway; VH, ventral horn. Asterisks, groups of neuron cell bodies of either parasympathetic preganglionic neurons or somatic motoneurons.



Figure 7.

Pathway taken by sympathetic afferent neurons from GI tract to CNS, primarily in midlumbar segments of spinal cord, cc, Central canal; DH, dorsal horn; DR, dorsal root; DRG, dorsal root ganglion; LCP, lateral collateral pathway; LS, lumbar splanchnic nerve; LT, Lissauer's tract; L3, L4, L5, lumbar spinal cord segments 3–5; MCP, medial collateral pathway; SG, sympathetic chain ganglion; VH, ventral horn; VR, ventral root. Asterisks, groups of preganglionic sympathetic neurons.

From Barone et al. 22


Figure 8.

Pudendal afferent neurons that arise primarily from area of external anal sphincter. Neurons travel by way of pudendal nerves into lower lumber (L7) segments 1–3 of sacral spinal cord. Afferents enter Lissauer's tract (LT) and give rise to medial and lateral collateral pathways (LCP) that terminate near the dorsal band (DB) of preganglionic neurons. Other afferents pass upward through dorsal funiculus to reach nucleus gracilis in the brain stem. DH, dorsal horn; DRG, dorsal root ganglion; VH, ventral horn.



Figure 9.

Distribution of fast blue‐labeled neurons in right (upper) and left (lower) dorsal motor nucleus of vagus (DMV) after fast blue injections into antrum and pylorus. Vertical axis, number of labeled cell bodies in DMV per 0.14 mm (sum of 5 serial 28‐μm sections). Horizontal axis, location in DMV (relative to obex in mm) of number of cell bodies.

From Pagani et al. 245


Figure 10.

Effect of electrical Stimulation (100 μA, 50 Hz, 0.2‐ms pulse duration) of dorsal motor nucleus of vagus on gastric motility and cardiovascular function. Arrow, stimulus was turned on. Small change in heart rate (HR).

From Pagani et al. 245


Figure 11.

Coronal section of brain stem passing through dorsal motor nucleus of vagus. Lesion site lies confined to dorsal medial aspect of dorsal motor nucleus of vagus (X). Electrical stimulation at that site produced the increase in contractile activity observed in Figure 10. mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.

From Pagani et al. 245


Figure 12.

Effect of electrical stimulation of 4 specific regions of dorsal motor nucleus of vagus on minute motility index (MMI). Cross‐hatched bars, changes in MMI of antrum; solid bars, changes in MMI of pylorus. Vertical bars, standard error of the mean. Data from each histogram were derived from 4–6 animals. Small asterisks, response was statistically significant (P < 0.05) from control using paired t test. Large asterisks, response was significantly (P < 0.05) attenuated compared with maximal response occurring from 1.5 to 2.0 mm rostral to obex using t test for grouped data.

From Pagani et al. 245


Figure 13.

Comparison of changes in minute motility index (MMI) induced by electrical stimulation of dorsal motor nucleus of vagus (DMV; left) and of brain sites medial to DMV (right). Cross‐hatched bars, changes in MMI of antrum; solid bars, changes in MMI of pylorus. Vertical bars, standard error of the mean. Data for each histogram were derived from 5–10 animals.

Adapted from Pagani et al. 245


Figure 14.

Coronal section of brain stem passing through dorsal motor nucleus of vagus (DMV). Lesion site lies medial to DMV (X). mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.

From Pagani et al. 245


Figure 15.

Experiment showing effect of microinjection of L‐glutamic acid (arrow) into dorsal motor nucleus of vagus on gastric motility and cardiovascular function.

From Gillis et al. 90


Figure 16.

Coronal section of brain stem passing through dorsal motor nucleus of vagus (DMV). Microinjection site lies in DMV X. mnTS, medial nucleus tractus solitarius; TS, tractus solitarius; XII, hypoglossal nucleus.



Figure 17.

Cross section of brainstem, 2.3 mm rostral to obex, that shows relationship of neuronal axons from nucleus ambiguus (NA) to dorsal motor nucleus of vagus (DMV) as they exit the brain stem. 10, inferior olivary nucleus; SpTr V, spinal tract of trigeminal nerve; TS, tractus solitarius; XII, hypoglossal nucleus.



Figure 18.

Effect of electrical stimulation (133 μA, 50 Hz, 0.2‐ms pulse duration) of nucleus ambiguus complex on gastric secretion (gastric pH, microe‐quivalents of H+, and peptic units), gastroduodenal motility, arterial pressure, and heart rate (HR). Left panels: control traces and values. Right panels: traces obtained immediately after electrical stimulation was initiated (arrows). Values for pH, microequivalents of H+, and peptic units are values obtained either over a 10‐min control collective period (left) or over a 10‐min period of electrical stimulation on nucleus ambiguus complex (right). MMI, minute motility index.

From Pagani et al. 244


Figure 19.

Coronal section of brain stem passing through nucleus ambiguus (arrow), tractus solitarius (TS), dorsal motor nucleus of vagus (X), hypoglossal nucleus (XII), and inferior olivary nucleus (IO).

Adapted from Pagani et al. 244


Figure 20.

Thoracolumbar portion of the spinal cord showing intermediate gray matter and its subnuclear groups, connection of upper thoracic segments of spinal cord to cervical ganglia of sympathetic chain, and connection of lumbar segments of spinal cord to lumbar part of the sympathetic chain. CA, central autonomic neurons; CC, central canal; IC, spinal intercalated nucleus; IMLf, funicular part of intermediolateral cell column; IMLp, principal part of intermediolateral cell column.



Figure 21.

Diagram of CNS demonstrating pathways that interconnect different nuclei that are involved in control of the GI system. A: overall wiring diagram. B: enlargement of medullary segment to show interconnections of dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA), nucleus tractus solitarius (NTS), medullary reticular formation (MRF), ventrolateral medulla (VLM), and raphe obscurus (RO). ACh, acetylcholine; NC, nucleus cuneatus; ON, Onuf's nucleus; SpTr V, spinal tract of trigeminal nerve.



Figure 22.

Proposed scheme of CNS neural pathways activated by blockade of effects of GABA in periventricular nucleus of the hypothalamus, resulting in increases in gastric motility and antagonism of vagal effects on the heart. We propose that blockade of GABAergic transmission occurs at interneurons located in the hypothalamus and results in activation of neurons projecting to GABA‐inhibitory interneurons located in the region of nucleus ambiguus (NA), as well as activation of a collateral branch of the same neuron that projects to excitatory interneurons in the dorsal motor nucleus of vagus (DMV). End result is an increase in parasympathetic outflow to the stomach and a decrease in parasympathetic outflow to the heart.

Adapted from Pagani et al. 243


Figure 23.

Proposed scheme showing how blockade of sympathetic nervous system activity to the colon can result in colonic contractions. Presumably enteric ganglia cells are active and are responsible for tonic release of acetylcholine (ACh) at smooth muscle of colon. In addition, tonic sympathetic activity originating from the spinal cord results in release of norepinephrine (NE) at enteric ganglia. Released NE acts on α2‐adrenergic receptors located on enteric ganglia cells to cause hyperpolarization and inhibit release of ACh. Blockade of α2‐adrenergic receptors removes this inhibitory noradrenergic input and results in cholinergically mediated increases in colonic motility. IML, intermediolateral cell column.

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Richard A. Gillis, John A. Quest, Francis D. Pagani, Wesley P. Norman. Control centers in the central nervous system for regulating gastrointestinal motility. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 621-683. First published in print 1989. doi: 10.1002/cphy.cp060117