Stimulus Luminance Research Articles

Pupil Response to Color Signals in Cone-Contrast Space

Purpose: It is widely accepted that pupil responses to visual stimuli are determined by the ambient illuminance, and recently it has been shown that changes in stimulus color also contributes to a pupillary control mechanism. However, the role of pupillary responses to chromatic stimuli is not clear. The aim of this study was to investigate how color and luminance signals contribute to the pupillary control mechanism. Methods: We measured pupillary iso-response contours in M-and L-cone contrast space. The iso-response contours in cone-contrast space have been determined to examine what mechanisms contribute to the pupillary pathway. The shapes of the iso-response contour change when different mechanisms determine the response. Results: It was shown that for all subjects, the pupillary iso-response contours form an ellipse with positive slope in cone-contrast space, indicating that the sensitivities to the chromatic stimuli are higher than those for the luminance stimuli. The pupil responds maximally to a grating that has a stronger L-cone modulation than the red-green isoluminant grating. Conclusions: The sensitivity of the chromatic pathway, in terms of pupillary response, is three times larger than that of the luminance pathway, a property that might have utility in clinical applications.

Orientation-Selective Adaptation to First- and Second-Order Patterns in Human Visual Cortex

Second-order textures-patterns that cannot be detected by mechanisms sensitive only to luminance changes-are ubiquitous in visual scenes, but the neuronal mechanisms mediating perception of such stimuli are not well understood. We used an adaptation protocol to measure neural activity in the human brain selective for the orientation of second-order textures. Functional MRI (fMRI) responses were measured in three subjects to presentations of first- and second-order probe gratings after adapting to a high-contrast first- or second-order grating that was either parallel or orthogonal to the probe gratings. First-order (LM) stimuli were generated by modulating the stimulus luminance. Second-order stimuli were generated by modulating the contrast (CM) or orientation (OM) of a first-order carrier. We used four combinations of adapter and probe stimuli: LM:LM, CM:CM, OM:OM, and LM:OM. The fourth condition tested for cross-modal adaptation with first-order adapter and second-order probe stimuli. Attention was diverted from the stimulus by a demanding task at fixation. Both first- and second-order stimuli elicited orientation-selective adaptation in multiple cortical visual areas, including V1, V2, V3, V3A/B, a newly identified visual area anterior to dorsal V3 that we have termed LO1, hV4, and VO1. For first-order stimuli (condition LM:LM), the adaptation was no larger in extrastriate areas than in V1, implying that the orientation-selective first-order (luminance) adaptation originated in V1. For second-order stimuli (conditions CM:CM and OM:OM), the magnitude of adaptation, relative to the absolute response magnitude, was significantly larger in VO1 (and for condition CM:CM, also in V3A/B and LO1) than in V1, suggesting that second-order stimulus orientation was extracted by additional processing after V1. There was little difference in the amplitude of adaptation between the second-order conditions. No consistent effect of adaptation was found in the cross-modal condition LM:OM, in agreement with psychophysical evidence for weak interactions between first- and second-order stimuli and computational models of separate mechanisms for first- and second-order visual processing.

The Perception of Motion in Chromatic Stimuli

The issue of whether there is a motion mechanism sensitive to purely chromatic stimuli has been pertinent for the past 30 or more years. The aim of this review is to examine why such different conclusions have been drawn in the literature and to reach some reconciliation. The review critically examines the behavioral evidence and concludes that there is a purely chromatic motion mechanism but that it is limited to the fovea. Examination of motion performance for chromatic and luminance stimuli provides convincing evidence that there are at least two different mechanisms for the two kinds of stimuli. The authors further argue that the chromatic mechanism may be at a particular disadvantage when the integration of multiple local motion signals is required. Finally, the authors present a descriptive model that may go some way toward explaining the reasons for the differences in collected data outlined in this article.

Color assimilation: Dependence of watercolor spreading on contour luminance contrast and stimulus width

Color assimilation: Dependence of watercolor spreading on contour luminance contrast and stimulus width

Centering biases in heterochromatic brightness matching

When the method of constant stimuli is used to measure heterochromatic brightness matches, the resulting matches can be strongly biased toward the center of the range of test luminances used [Teller, D. Y., Pereverzeva, M., & Civan, A. L. (2003). Adult brightness vs. luminance as models of infant photometry: variability, biasability, and spectral characteristics for two age groups favor the luminance model. Journal of Vision, 3, 333–346]. In the present paper, we investigate the source of this centering bias. The stimuli were 2° red squares presented in a gray surround. In the main experiments, two ranges of stimulus luminance were presented in separate physical locations on a video monitor, but with test trials interleaved in time. Subjects either fixated a fixation cross (fixation condition), creating different retinotopic locations for the two luminance ranges, or foveated each stimulus as it appeared (foveation condition), creating identical retinotopic locations for both ranges. In the fixation condition, the two different stimulus sets resulted in a simultaneous centering bias—two different brightness matches at two different retinotopic locations at the same time. This effect was essentially eliminated in the foveation condition. A dichoptic foveation condition also revealed no centering bias. The results suggest that under the conditions tested, the centering bias is caused by a process located at a post-retinal but still retinotopically organized level of the visual system, rather than by either a retinal process or a more central, spatiotopically organized one.

Cone signal interactions in direction-selective neurons in the middle temporal visual area (MT)

Many experimental measurements support the hypothesis that the middle temporal visual area (MT) of the rhesus monkey has a central role in processing visual motion. Most of these studies were performed using luminance stimuli, leaving open the question of how color information is used during motion processing. We investigated the specific question of how S-cone signals, an important source of color information, interact with L,M-cone signals, the dominant source of luminance information. In MT, S-cone-initiated signals combine synergistically with L,M-cone (luminance) signals over most of the stimulus range, regardless of whether the stimuli are added or subtracted. A quantitative analysis of the responses to the combination of S- and L,M-cone signals shows that for a significant minority of cells, these S-cone signals are carried to MT by a color-opponent ("blue-yellow") pathway, such that in certain limited contrast ranges, a small amount of S- and L,M-cone cancellation is observed. Both S- and L,M-cone responses are direction-selective, suggesting that MT processes a wide range of motion signals, including those carried by luminance and color. To investigate this possibility further, we measured MT responses while monkeys discriminated the direction of motion of luminance and S-cone-initiated gratings. The sensitivity of single MT neurons and the correlation between trial-to-trial variations in single neuron firing and perception are similar for S- and L,M-cone stimuli, further supporting a role for MT in processing chromatic motion.

The Binocular Combination of Chromatic Contrast

How is chromatic contrast combined binocularly? One index of binocularity is the binocular contrast summation ratio (BCSR), which is the improvement in contrast sensitivity with binocular rather than monocular presentation. Simmons and Kingdom (1998, Vision Research 38 1063-1071) noted that BCSRs with some red-green isoluminant stimuli were suggestive of full linear summation. This suggestion was investigated further in four subjects by measuring binocular and monocular contrast thresholds for the detection of 0.5 cycle deg(1) isoluminant (red-green) and isochromatic (yellow-black) Gabor patches. These Gabor patches had either vertically or horizontally oriented carrier gratings and were either dichoptically in phase (same coloured bars in binocular correspondence) or in dichoptic anti-phase (opposite coloured bars in binocular correspondence). Full linear summation would be indicated by BCSRs of 2 for the in-phase and close to 0 for the anti-phase conditions. Mean BCSRs at isoluminance were 1.93 and 0.90, respectively, for the in-phase and anti-phase stimuli with horizontal carriers, the former being consistent with full linear summation, but the latter not. Despite these results, BCSRs obtained with isoluminant and isochromatic stimuli under similar conditions were not statistically distinguishable from each other, although there was a tendency for summation at isoluminance with in-phase stimuli to be higher and anti-phase stimuli to be lower. These data fall short of demonstrating full linear summation of chromatic contrast between the eyes under all presentation conditions, but they do indicate that there are strong binocular interactions at red-green isoluminance, which are similar to, and possibly even stronger than, those obtained with luminance stimuli.

Factors Influencing Reaction Time during Automated Kinetic Perimetry on the Tübingen Computer Campimeter

To determine the effect of age, examination, location, luminance, subject, and vigilance on reaction time (RT) in automated kinetic perimetry. Thirty-six normal volunteers (20-70 years old) underwent kinetic campimetric examinations, during which RTs (time from appearance of a stimulus to response) were recorded. Stimuli with a diameter of 26 minutes of arc (Goldmann III) were presented on horizontal vectors with an angular velocity of 2 deg/s. Thirty-two positions in the 30 degrees radius visual field were tested six times, at luminance levels of 41.62 and 110 cd/m2 (background 10 cd/m2). An analysis of RT variance (ANCOVA) was performed. Median RT increased with age from 370 ms (20-30-year-old subjects) to 440 ms (60-70-year-old subjects). There was a strong dependency of RT from the individual subjects examined (means range, 313-411 ms), from the course of one examination period, from the examination and stimulus luminance, and from the location in the visual field. Reaction time during automated kinetic perimetry varies considerably. This study shows that the factors of age, the subject examined, his or her daily condition, the course within one examination period, and the stimulus location and luminance are of relevance. For a much more reliable prediction of individual RTs and thus a precise assessment of local kinetic thresholds, application of some additional kinetic stimuli (RT time vectors) within the intact visual field areas is necessary.

Computational neurobiology of the flash-lag effect

In the flash-lag effect (FLE) a moving object is perceived ahead of a stationary stimulus flashed in spatial alignment. Several explanations have been proposed to account for the FLE and its dependence on a variety of psychophysical attributes. Here, we show that a simple feed-forward network reproduces the standard FLE and several related manifestations, such as its modulation by stimulus luminance, trajectory, priming, and spatial predictability. A minimal set of elements, based on plausible neuronal mechanisms, yields a unified account of these visual illusions and possibly other perceptual phenomena.

Effects of diazepam on the latency of saccades for luminance and binocular disparity defined stimuli

Saccadic latency is composed of separate sensory and motor processing delays. Therefore, any alteration in the sensory processing should effect the saccadic latency. Because the highest density of benzodiazepine (Bz) binding sites is located in cerebral cortex, sensory processing of stimuli in this cortical area is expected to be substantially effected by administration of Bzs. It is well known that sensory processing of binocular disparity occurs in the cerebral cortical areas and therefore the latency of saccades to stimuli defined by binocular disparity should be substantially affected by Bz intake. In this study, we tested this prediction by comparing the latency of saccadic eye movements for binocular disparity defined stimuli (stereo stimuli) with those for luminance contrast defined stimuli (luminance stimuli), after diazepam or placebo. Eye movements were mainly recorded by use of the magnetic search coil technique, and the study was performed in a randomized, double-blind way. Although diazepam prolonged the latency of saccades for stereo and luminance stimuli, the percentage increases in saccadic latency for the stereo stimuli were significantly larger than those for the luminance stimuli. Saccadic peak velocity, and saccadic amplitude, also significantly decreased after diazepam under conditions of stereo and luminance stimuli. However, there was no significant difference for either saccadic peak velocity or amplitude between the two types of target. The results suggest that the latency of saccades to binocular disparity defined random-dot stimuli could more sensitively reflect the pharmacodynamic effects of Bzs on the cerebral cortex.

Habituation of Retinal Ganglion Cell Activity in Response to Steady State Pattern Visual Stimuli in Normal Subjects

To evaluate autoregulatory changes of retinal ganglion cell (RGC) activity, as measured by the pattern electroretinogram (PERG), when the eye is exposed to a steady state presentation of stimuli that maximize PERG amplitude and blood flow. The PERG was recorded from both eyes of 14 normal subjects in response to steady state presentation (4 minutes) of contrast-reversing (16.28/s) gratings (1.6 cyc/deg) with different contrast (12%-99%) and mean luminance (40-1.3 cd/m(2)). One temporal period of the stimulus (122.8 ms) was sampled and averaged in packets of 50 sweeps ( approximately 15 seconds each). PERG amplitude and phase were evaluated by Discrete Fourier Transform and displayed as a function of time. Data were fitted with an exponential decay function to evaluate PERG changes with time. For patterns of 99% contrast, the PERG amplitude progressively decreased with time until reaching a plateau approximately 30% lower than the initial amplitude after approximately 2 minutes (habituation). The ratio between initial and plateau amplitude did not change by reducing the stimulus luminance by 1 log unit. However, reducing contrast decreased amplitude habituation. The habituation was abolished at 25% contrast. Decrease of PERG amplitude with time is consistent with a slow adaptive change of RGC activity in response to high-contrast, steady state stimuli. The authors propose that the initial amplitude represents an index of RGC activity, and the plateau amplitude represents a dynamic equilibrium between RGC activity and the available energy supply. These results are relevant for a better understanding of glaucomatous optic neuropathy.

Loss of visual information in neglect: the effect of chromatic- versus luminance-contrast stimuli in a “what” task

One to four vertical bars were tachistoscopically presented at various eccentricities along the horizontal meridian to patients with right brain damage and neglect (n=7) and to a control group of right brain damaged patients without neglect (n=4). Luminance contrast stimuli and isoluminant chromatic contrast stimuli were used. The patients' task was to report the number of bars. With luminance stimuli the neglect patients' discrimination in the left visual field was reduced, particularly at the most leftward position tested (ca 20 degrees ) where about 20% of the bars were omitted. The loss of information was limited to luminance contrast stimuli. When chromatic contrast stimuli were used, accuracy was comparable in the two hemifields and between groups of patients. The differential pattern of results for chromatic and luminance contrast stimuli is consistent with the hypothesis of a selective deficit of the magno-cellular pathway in neglect.

Calculation Method For Visibility Of Emergency Sign In Fire Taking Into Account Of Smoke Adherence

In making a plan for safe evacuation under smoke in fire, visibility of evacuation signs is of crucial significance. However, there have been very few studies on the calculation method for the luminous stimuli in fire smoke, thereby leaving effective evacuation methodology unattained. In fire situation, we have to consider factors affecting sign’s visibility such as power failure, obscuration by smokes and smoke adhesion to the sign surface or light sources. In order for emergency signs to function properly for evacuation, we need to assure the sufficient visibility in every situation. Therefore it is necessary to establish a calculation method of luminous stimuli in fire smoke to evaluate evacuee’s visibility quantitatively. This paper proposes a calculation model of target luminance in fire-smoke taking into account of smoke adhesion. Practical application is also presented.

Effects of Color and Luminance Stimuli on Kanizsa Shrinkage Illusion

Effects of Color and Luminance Stimuli on Kanizsa Shrinkage Illusion

Optotype and Grating Visual Acuity in Patients with Ocular and Cerebral Visual Impairment

To investigate the discrepancy between grating and optotype visual acuity in children with visual impairment due to brain and/or ocular abnormalities. Better eye acuity at 114 cm was studied in 81 patients (ages, 5-24 years) attending special schools for the visually handicapped. Fourteen patients had a brain abnormality, 48 had an ocular disorder, and 19 had both. Three acuity tasks were administered: detecting gratings in one of two positions, discriminating the orientation of single gratings, and discriminating the orientation of uncrowded Landolt-C optotypes. The three paradigms were similar in stimulus contrast, luminance, presentation mode, and psychophysical procedure. Overall, grating acuity was better than optotype acuity, and the disparity increased with poorer optotype acuity. The largest discrepancies occurred in patients with brain abnormality, but disparities were also large in patients with optic nerve disorder. In patients with ocular and brain abnormality, grating acuities were only mildly better and not different from patients with only ocular abnormality. Grating orientation and grating detection tasks yielded similar thresholds, except in patients with cerebral visual impairment and with optic nerve disorder, whose grating detection acuity was better than grating orientation acuity. Grating-to-optotype acuity superiority is typically large in visual disorders involving the brain. The closely matched test paradigms point to stimulus characteristics as the explanation. However, because the discrepancy decreased with grating orientation acuity instead of grating detection acuity, the complexity of the response required also plays a role.

Isolated Lymphoid Follicles Can Function as Sites for Induction of Mucosal Immune Responses

Isolated lymphoid follicles (ILFs) are organized lymphoid structures in the small intestine. ILFs were recently identified in the murine small intestine; however, the function of ILFs is unknown. To better understand ILFs and the role they play in the intestinal immune response, we have examined the composition of ILFs, the factors that are involved in the genesis of ILFs, and the ability of ILFs to support antigen-specific immunoglobulin production. We found that ILFs contain predominantly B-2 B lymphocytes, and CD4(+) TCRbeta(+) T lymphocytes. Similar to the formation of Peyer's patches (PPs), lymphotoxin beta receptor (LTbetaR)-dependent events are required for ILF formation; however, the timing of these events and the cellular source of LT differ. ILF formation can occur de novo in response to luminal stimuli and requires LT-sufficient B lymphocytes and TNF receptor I function for full maturation. The epithelium over ILFs resembles the PP follicle-associated epithelium, as M cells are present and pathogens such as Yersinia can be bound and taken up into the underlying follicle. Total fecal IgA production is not augmented in animals possessing ILFs; however, the production of antigen-specific IgA is increased in animals possessing ILFs orally challenged with Salmonella typhimurium. Similar to PPs, ILFs can support antigen-specific IgA production following oral immunization. These findings support the concept that ILFs are formed in response to mucosal challenges, and may play a physiological role in the production of antigen-specific intestinal IgA.

Neurochemical phenotype of vagal afferent neurons activated to express C-FOS in response to luminal stimulation in the rat

The vagus nerve conveys meal-induced primary afferent responses to the brainstem. Electrophysiological studies indicate that luminal stimuli such as osmolarity and the digestion products of carbohydrates elicit powerful vagal nodose neuronal responses by activating serotonin 3 (5-hydroxytryptamine-3, 5-HT 3) receptors on intestinal mucosal afferent fibers. To characterize the neurochemical phenotype of neurotransmitters in vagal nodose neurons that are activated by luminal stimulation, we examined c- fos protein (c-Fos) expression in response to luminal stimulation in conscious rats. A double-labeling technique using antisera to glutamate (Glu), substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SS) was used to determine the neurochemical profile of c-Fos-positive neurons. c-Fos immunoreactivity was insignificant in vehicle-treated rats. Luminal perfusions of NaCl (500 mOsm), tap water (5 mOsm), maltose (300 mmol/l), and 5-HT (10 −5 mol/l) each elicited a significant increase in the number of cells expressing c-Fos. Chronic vagotomy eliminated an increase in nodose neuronal c-Fos expression, and the 5-HT 3 receptor antagonist granisetron significantly reduced it. Glu-, SP-, and CGRP-containing neurons represented 28%, 53%, and 19%, respectively, of the total population of nodose neurons. Few neurons contained SS. Double-labeling studies revealed that of the c-Fos-positive neurons responsive to hypertonic NaCl, 52%, 41%, and 3% exhibited immunoreactivity for Glu, SP, and CGRP, respectively. Of those responsive to tap water, 47%, 50%, and 4% exhibited immunoreactivity for Glu-, SP- and CGRP, respectively. In addition, 44%, 38%, and 8% of 5-HT-stimulated and 30%, 32%, and 5% of maltose-stimulated c-Fos-positive neurons exhibited, respectively, Glu, SP, and CGRP immunoreactivity. The few neurons that contained SS did not express c-Fos. Conclusions: Vagal primary afferent neurons that respond to 5-HT-dependent luminal stimuli, such as hyperosmolarity and maltose, contain mainly Glu and SP. These neurons appear to play an important role in the mediation of the vago-vagal reflex elicited by luminal stimuli.

Peaked Encoding of Relative Luminance in Macaque Areas V1 and V2

It is widely presumed that throughout the primate visual pathway neurons encode the relative luminance of objects (at a given light adaptation level) using two classes of monotonic function, one positively and the other negatively sloped. Based on computational considerations, we hypothesized that early visual cortex also contains neurons preferring intermediate relative luminance values. We tested this hypothesis by recording from single neurons in areas V1 and V2 of alert, fixating macaque monkeys during presentation of a large, spatially uniform patch oscillating slowly in luminance and surrounded by a static texture background. A substantial subset of neurons responsive to such low spatial frequency luminance stimuli in both areas exhibited prominent and statistically reliable response peaks to intermediate rather than minimal or maximal luminance values. When presented with static patches of different luminance but of the same spatial configuration, most neurons tested retained a preference for intermediate relative luminance. Control experiments using luminance modulation at multiple low temporal frequencies or reduced amplitude indicate that in the slow luminance-oscillating paradigm, responses were more strongly modulated by the luminance level than the rate of luminance change. These results strongly support our hypothesis and reveal a striking cortical transformation of luminance-related information that may contribute to the perception of surface brightness and lightness. In addition, we tested many luminance-sensitive neurons with large chromatic patches oscillating slowly in luminance. Many cells, including the gray-preferring neurons, exhibited strong color preferences, suggesting a role of luminance-sensitive cells in encoding information in three-dimensional color space.

Review article: serotonin receptors and transporters — roles in normal and abnormal gastrointestinal motility

The gut is the only organ that can display reflexes and integrative neuronal activity even when isolated from the central nervous system. This activity can be triggered by luminal stimuli that are detected by nerves via epithelial intermediation. Epithelial enterochromaffin cells act as sensory transducers that activate the mucosal processes of both intrinsic and extrinsic primary afferent neurones through their release of 5-hydroxytryptamine (5-HT). Intrinsic primary afferent neurones are present in both the submucosal and myenteric plexuses. Peristaltic and secretory reflexes are initiated by submucosal intrinsic primary afferent neurones, which are stimulated by 5-HT acting at 5-HT(1P) receptors. 5-HT acting at 5-HT4 receptors enhances the release of transmitters from their terminals and from other terminals in prokinetic reflex pathways. Signalling to the central nervous system is predominantly 5-HT3 mediated, although serotonergic transmission within the enteric nervous system and the activation of myenteric intrinsic primary afferent neurones are also 5-HT3 mediated. The differential distribution of 5-HT receptor subtypes makes it possible to use 5-HT3 antagonists and 5-HT4 agonists to treat intestinal discomfort and motility. 5-HT3 antagonists alleviate the nausea and vomiting associated with cancer chemotherapy and the discomfort from the bowel in irritable bowel syndrome; however, because 5-HT-mediated fast neurotransmission within the enteric nervous system and the stimulation of mucosal processes of myenteric intrinsic primary afferent neurones are 5-HT3 mediated, 5-HT3 antagonists tend to be constipating and should be used only when pre-existing constipation is not a significant component of the problem to be treated. In contrast, 5-HT4 agonists, such as tegaserod, are safe and effective in the treatment of irritable bowel syndrome with constipation and chronic constipation. They do not stimulate nociceptive extrinsic nerves nor initiate peristaltic and secretory reflexes. Instead, they rely on natural stimuli to activate reflexes, which they strengthen by enhancing the release of transmitters in prokinetic pathways. Finally, when all the signalling by 5-HT is over, its action is terminated by uptake into enterocytes or neurones, which is mediated by the serotonin reuptake transporter. In inflammation, serotonergic signalling is specifically diminished in the mucosa. Transcripts encoding tryptophan hydroxylase-1 and serotonin reuptake transporter are both markedly decreased. Successive potentiation of 5-HT and/or desensitization of its receptor could account for the symptoms seen in diarrhoea-predominant and constipation-predominant irritable bowel syndrome, respectively. Symptoms associated with the down-regulation of the serotonin reuptake transporter in the human mucosa in irritable bowel syndrome are similar to the symptoms associated with the knockout of the serotonin reuptake transporter in mice. The observation that molecular defects occur in the human gut in irritable bowel syndrome strengthens the hand of those seeking to legitimize the disease. At least it is not 'all in your head'. The bowel contributes.

Developmental biology of the enteric nervous system: Pathogenesis of Hirschsprung’s disease and other congenital dysmotilities

Congenital diseases of dysmotility are a serious problem in children and, potentially, also in adults. Advances have recently been made in understanding one cause of pediatric dysmotility, Hirschsprung’s disease, which is the most visible congenital defect of the enteric nervous system (ENS).1–5 Although the diagnosis of Hirschsprung’s disease is sometimes missed, and the length of involved gut may vary,6,7 a segment of bowel is always totally aganglionic in patients with Hirschsprung’s disease, which is about an unsubtle as a defect can be. The ENS, however, can be abnormal without being aganglionic. This is true because the function of the ENS is much more sophisticated than that of other regions of the autonomic nervous system.8 The output of the ENS is not a simple binary choice to drive motility or not, or to stimulate secretion or not. The ENS is responsible for the integrative control of behavior, a function that is sufficiently complex as to require all of the classes of neurotransmitter found in the CNS and at least as many neurons as are found in the spinal cord (~108 in humans).4,9–12 The ENS does not simply accept commands from the brain and spinal cord, it also talks back to the CNS. The transfer of information between the bowel and the brain in the vagus nerves is two-way process and in fact, many more vagal fibers are afferent than efferent.13 Vagus nerve stimulation can be employed to affect epilepsy,14–16 treat depression16–18 and even to improve learning and memory.19 To function normally, therefore, the ENS requires a full panoply of neurons of correct phenotypes, proper synaptic connections, and an appropriate interaction with the CNS. More is needed of development, therefore, than just to produce relay ganglia to enable the brain to drive the gut. Despite the progress made in comprehending the aganglionosis of Hirschsprung’s disease, little is known about subtle abnormalities in subsets of enteric neurons, ENS synapses, or in the establishment of CNS-ENS interactions. Aganglionosis of the type seen in Hirschsprung’s disease cannot be the cause of functional bowel diseases, which are not lethal and are not associated with pseudoobstruction. If there is a developmental defect that causes functional bowel diseases, that defect has to be compatible with propulsive motility because propulsive motility occurs in patients with functional bowel diseases, even if the propulsive motility is so abnormal that the patient is driven to distraction. Abdominal distress from a bowel that propels may be particularly troublesome in children who may not be able to find a constructive means of conveying their difficulty. A congenital defect in the ENS that causes motility to be abnormal but present is likely to be one that affects committed sublineages of neural or glial precursors rather than pluripotent stem cells and thus to occur relatively late in ENS ontogeny.20 Such a late-arising, seemingly limited defect could also stop propulsive motility if it were to disrupt the function of a critical cell, such as the intrinsic primary afferent neurons (IPANs) that are required for the gut to be able to respond to luminal stimuli.21–25 Motility may then be compromised severely even when the pathology of the ENS, examined with conventional stains, is described as normal. This type of defect may be responsible for the still-to-be explained pediatric dysmotilities and chronic intestinal pseudoobstruction (CIP). This review is designed to examine the development of the ENS, not as a detailed catalogue of all known relevant phenomena, but to provide a conceptual basis for understanding, not only the pathogenesis of Hirschsprung’s disease, but also other disorders of dysmotility that are not associated with aganglionosis. Emphasis will be placed on genes that, when mutated, give rise to defects in the ENS that are not obvious but which nevertheless cause intestinal motility to become subtly or devastatingly abnormal.