The white matter of the brain consists of fiber tracts that connect different regions of the brain. Among these tracts, the intrahemispheric cortico-cortical connections are called association fibers. The U-fibers are short association fibers that connect adjacent gyri. These fibers were thought to work as part of the cortico-cortical networks to execute associative brain functions. However, their anatomy and functions have not been documented in detail for the human brain. In past studies, U-fibers have been characterized in the human brain with diffusion tensor imaging (DTI). However, the validity of such findings remains unclear. In this study, DTI of the macaque brain was performed, and the anatomy of U-fibers was compared with that of the human brain reported in a previous study. The macaque brain was chosen because it is the most commonly used animal model for exploring cognitive functions and the U-fibers of the macaque brain have been already identified by axonal tracing studies, which makes it an ideal system for confirming the DTI findings. Ten U-fibers found in the macaque brain were also identified in the human brain, with a similar organization and topology. The delineation of these species-conserved white matter structures may provide new options for understanding brain anatomy and function.

Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and perception; second, there are nonoverlapping neural networks: one might be involved in perception and the other for the VOR. We investigated these possibilities by measuring VOR and perceptual responses in healthy human subjects during whole-body, constant-velocity rotation steps about all three dimensions (yaw, pitch, and roll) before and after 10 mg of 4-aminopyridine (4-AP). 4-AP, a selective blocker of inward rectifier potassium conductance, can lead to increased synchronization and precision of Purkinje neuron discharge and possibly enhance the GABAergic action. Hence 4-AP could reduce the decay time constant of the perceived angular velocity and VOR. We found that 4-AP reduced the decay time constant, but the amount of reduction in the two processes, perception and VOR, was not the same, suggesting the possibility of nonoverlapping or partially overlapping neural substrates for VOR and perception. We also noted that, unlike the VOR, the perceived angular velocity gradually built up and plateau prior to decay. Hence, the perception pathway may have additional mechanism that changes the dynamics of perceived angular velocity beyond the velocity storage. 4-AP had no effects on the duration of build-up of perceived angular velocity, suggesting that the higher order processing of perception, beyond the velocity storage, might not occur under the influence of mechanism that could be influenced by 4-AP.

SUMMARY

Vertigo in and around MRI machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all healthy human subjects lying in the static magnetic field of an MRI machine develop a robust nystagmus. Patients lacking labyrinthine function do not. Here we use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation derives from a Lorentz force due to interaction between the magnetic field and naturally-occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupula’s function as a pressure sensor, makes magnetic field induced nystagmus and vertigo possible. Such effects could confound fMRI studies of brain behavior, including resting-state brain activity.

Measurement of eye movements often helps to diagnose ocular motor disorders in the clinic, and is also used as a research tool in ocular motor, vision and vestibular research. Eye movements, however, are usually recorded without simultaneous video recordings, making offline interpretation difficult. We developed a tool that converts the measured eye movement data into a three-dimensional (3D) movie of eye movements. Having useful functions such as slow-play, pause and exaggeration of the movements, this new software provides a research and teaching tool to aid interpretation of the recorded eye movements.

Conductance-based models of reciprocally inhibiting burst neurons suggest that intrinsic membrane properties and postinhibitory rebound (PIR) determine the amplitude and frequency of saccadic oscillations. Reduction of the low-threshold calcium currents (IT) in the model decreased the amplitude but increased the frequency of the simulated oscillations. Combined reduction of hyperpolarization-activated cation current (Ih) and IT in the model abolished the simulated oscillations. We measured the effects of a selective blocker of IT (ethosuximide) in healthy subjects on the amplitude and frequency of saccadic oscillations evoked by eye closure and of a nonselective blocker of Ih and IT (propronolol) in a patient with microsaccadic oscillation and limb tremor syndrome (mSOLT). Ethosuximide significantly reduced the amplitude but increased the frequency of the saccadic oscillations during eye closure in healthy subjects. Propranolol abolished saccadic oscillations in the mSOLT patient. These results support the hypothetical role of postinhibitory rebound, Ih, and IT, in generation of saccadic oscillations and determining their kinematic properties.

Background

Thoracoscopic repair of esophageal atresia is considered to be one of the more advanced pediatric surgical procedures, and it undoubtedly has a learning curve. This is a single-center study that was designed to determine the learning curve of thoracoscopic repair of esophageal atresia.

Methods

The study involved comparison of the first and second five-year outcomes of thoracoscopic esophageal atresia repair.

Results

The demographics of the two groups were comparable. There was a remarkable reduction of postoperative leakage or stenosis, and recurrence of fistulae, in spite of the fact that nowadays the procedure is mainly performed by young staff members and fellows.

Conclusions

There is a considerable learning curve for thoracoscopic repair of esophageal atresia. Centers with the ambition to start up a program for thoracoscopic repair of esophageal atresia should do so with the guidance of experienced centers.

When we applied a single pulse of transcranial magnetic stimulation (TMS) to any part of the human head during a saccadic eye movement, the ongoing eye velocity was reduced starting as early as 45ms after the TMS, and lasted around 32ms. The perturbation to the saccade trajectory was not due to a mechanical effect of the lid on the eye (e.g., from blinks). When the saccade involved coordinated movements of both the eyes and the lids, e.g., in vertical saccades, TMS produced a synchronized inhibition of the motor commands to both eye and lid muscles. The TMS induced perturbation of the eye trajectory did not show habituation with repetition, and was present in both pro- and anti-saccades. Despite the perturbation, the eye trajectory was corrected within the same saccade with compensatory motor commands that guided the eyes to the target. This within-saccade correction did not rely on visual input, suggesting that the brain monitored the oculomotor commands as the saccade unfolded, maintained a real time estimate of the position of the eyes, and corrected for the perturbation. TMS disrupted saccades regardless of the location of the coil on the head, suggesting that the coil discharge engages a non-habituating startle-like reflex system. This system affects ongoing motor commands upstream of the oculomotor neurons, possibly at the level of the superior colliculus or omnipause neurons. Therefore, a TMS pulse centrally perturbs saccadic motor commands, which are monitored possibly via efference copy, and are corrected via internal feedback.

Background

The CO2 pneumoperitoneum, which is used for laparoscopic surgery, causes local and systemic effects in patients. Concern arises about what the pressurized anoxic environment of the CO2 pneumoperitoneum has on intestinal healing. Earlier experimental work showed a negative correlation between intestinal healing and the applied intra-abdominal pressure. To further elucidate this, we developed a rat model, in which enterotomy healing can be compared after open or laparoscopic surgery. Possible mechanisms of injury, such as impaired neoangiogenesis or injury through hypoxia-induced pathways were studied.

Methods

A new experimental mechanically ventilated rat model was developed. An enterotomy was made and closed via laparotomy (group I) or laparoscopy under CO2 pressures of 5 mmHg (group II) or 10 mmHg (group III). Intestinal healing was tested in vivo after 1 week by bursting-pressure analysis. The effect of the operative procedure on neoangiogenesis was tested by counting factor VIII positive vessels in biopsies of the perianastomotic granulation tissue after 1 week. Intestinal anoxia was tested by quantifying HIF-1α protein levels in intestinal biopsies, taken before the enterotomy closure.

Results

The bursting pressures were significantly lower after laparoscopic surgery at 10 mmHg CO2 pneumoperitoneum (group III) compared with rats that had undergone open surgery (group I) or laparoscopic surgery at 5 mmHg CO2 pneumoperitoneum (group II). There was no significant quantitative difference between the three groups in the neoangiogenesis nor was there a difference in the amount of HIF-1α measured in the intestinal biopsies.

Conclusions

We developed a surgical model that is well fitted to study the effects of pneumoperitoneum on intestinal healing. With this model, we found further evidence of CO2 pressure-dependant hampered intestinal healing. These differences could not be explained by difference in neoangiogenesis nor local upregulation of hypoxic factors.

When environmental or sensory conditions change suddenly, the brain must be capable of learning different behavioral modes to produce accurate movements under multiple circumstances. A form of this dual-state adaptation known as “context-specific adaptation” has been widely investigated using the saccade gain adaptation paradigm in humans. In this study, we asked whether or not context-specific adaptation of saccade gain exists in monkeys and if so to explore its properties. Here, vertical eye position was used as a context cue for adaptation of horizontal saccade gain. We asked for a gain increase in one context and gain decrease in another context, and then determined if a change in the context would invoke switching between the adapted states. After training, our monkeys developed context-specific adaptation: in most cases gain-decrease adaptation could be induced, but there was little or no gain-increase adaptation. This context-specific adaptation developed gradually and switching of gains was evident on the first saccades with each change in context. Along with these results, the retention of an adaptation aftereffect overnight indicates that contextual-specific adaptation in monkeys is not a strategy, but involves a true adaptive process of reorganization in the brain. We suggest that context-specific adaptation in monkeys could be an important tool to provide insights into the mechanisms of saccade adaptation that occurs during the more natural circumstances of daily life.

Episodic ataxia (EA) syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. EA type 2 (EA2), the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel, and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4 and 40 kb in EA2. In 47 subjects with EA (26 with EA2-like features) who tested negative for mutations in the known EA genes, we used multiplex ligation-dependent probe amplification to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200 kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2.

An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural–functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: (1) the flocculus/paraflocculus for high-frequency (brief) vestibular responses, sustained pursuit eye movements, and gaze holding, (2) the nodulus/ventral uvula for low-frequency (sustained) vestibular responses, and (3) the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region) for saccades and pursuit initiation.

Background

Antireflux surgery (ARS) for gastroesophageal reflux disease (GERD) is one of the most frequently performed major operations in children. Many studies have described the results of ARS in children, however, with a wide difference in outcome. This study aims to systematically review the efficacy of pediatric ARS and its effects on gastroesophageal function, as measured by gastroesophageal function tests. This is the first systematic review comprising only prospective, longitudinal studies, minimizing the risk of bias.

Methods

Three electronic databases (Medline, Embase, and the Cochrane Library) were searched for prospective studies reporting on ARS in children with GERD.

Results

In total, 17 eligible studies were identified, reporting on a total of 1,280 children. The median success rate after ARS was 86% (57–100%). The success rate in neurologically impaired children was worse in one study, but similar in another study compared to normally developed children. Different surgical techniques (total versus partial fundoplication, or laparoscopic versus open approach) showed similar reflux recurrence rates. However, less postoperative dysphagia was observed after partial fundoplication and laparoscopic ARS was associated with less pain medication and a shorter hospital stay. Complications of ARS varied from minimal postoperative complications to severe dysphagia and gas bloating. The reflux index (RI), obtained by 24-h pH monitoring (n = 8) decreased after ARS. Manometry, as done in three studies, showed no increase in lower esophageal sphincter pressure after ARS. Gastric emptying (n = 3) was reported either unchanged or accelerated after ARS. No studies reported on barium swallow x-ray, endoscopy, or multichannel intraluminal impedance monitoring before and after ARS.

Conclusion

ARS in children shows a good overall success rate (median 86%) in terms of complete relief of symptoms. Efficacy of ARS in neurologically impaired children may be similar to normally developed children. The outcome of ARS does not seem to be influenced by different surgical techniques, although postoperative dysphagia may occur less after partial fundoplication. However, these conclusions are bound by the lack of high-quality prospective studies on pediatric ARS. Similar studies on the effects of pediatric ARS on gastroesophageal function are also very limited. We recommend consistent use of standardized assessment tests to clarify the effects of ARS on gastroesophageal function and to identify possible risk factors for failure of ARS in children.

Background

Since the initial reports of laparoscopic repair of duodenal atresia in neonates, further reports have been scant. Could this be because of unacceptable rates of complications, like anastomotic leakage, as mentioned in later reports? In the present study the laparoscopic repair of duodenal atresia in neonates is revisited.

Patients

Group 1 consisted of 22 patients with duodenal obstruction between 2000–2005 until the laparoscopic approach was abandoned. Of these 22 patients, 10 had Down syndrome and 8 had concomitant malformations. In this group 18 patients were operated laparoscopically. Four patients underwent an open procedure. Group 2 consisted of six patients that underwent operation between 2008 and February 2010.

Results

In group 1 there were four conversions. In 14 patients the procedure could be completed laparoscopically. In five patients postoperative leakage occurred. The complication rate was found to be unacceptably high, and the laparoscopic approach was abandoned. After gaining additional experience in intracorporeal suturing and adjusting the technique, the procedure was started up again in 2008. Since then six consecutive neonates have undergone laparoscopic repair of duodenal atresia without complications.

Conclusions

Laparoscopic repair of duodenal atresia is one of the most demanding pediatric laparoscopic surgical procedures. After initial promising results at the beginning of the twenty-first century a relative “radio silence“ followed, apparently caused by unsatisfactory results. Only considerable adjustments in technique and extensive improvement in experience has led to acceptable outcomes more recently. Laparoscopic repair of duodenal atresia should therefore be restricted to pediatric centers with extensive experience in laparoscopic surgery and intracorporeal suturing.

We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the “4 D’s”: correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the “7 A’s”) that can be used: antiemetics; anti-inflammatory, anti-Ménière’s, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Ménière’s disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal “pacemaker” activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Ménière’s disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine.

Objective

To examine patterns of executive and oculomotor control in a group of both boys and girls with attention-deficit/hyperactivity disorder (ADHD).

Method

Cross-sectional study of 120 children aged 8 to 12 years, including 60 with ADHD (24 girls) and 60 typically developing controls (29 girls). Oculomotor paradigms included visually guided saccades (VGS), antisaccades, memory-guided saccades, and a go/no-go test, with variables of interest emphasizing response preparation, response inhibition, and working memory.

Results

As a group, children with ADHD demonstrated significant deficits in oculomotor response preparation (VGS latency and variability) and response inhibition but not working memory. Girls, but not boys with ADHD, had significantly longer VGS latencies, even after controlling for differences in ADHD symptom severity. The ADHD subtypes did not differ on response preparation or inhibition measures; however, children with the Inattentive subtype were less accurate on the working memory task than those with the Combined subtype.

Conclusions

Sex differences in children with ADHD extend beyond symptom presentation to the development of oculomotor control. Saccade latency may represent a specific deficit among girls with ADHD.

The diagnosis of superior oblique palsy is commonly invoked to explain acquired diplopia, but the clinical features of this form of cyclovertical strabismus are inconsistent and poorly understood. The primate model of acquired superior oblique palsy reported in this article provides surprising anatomic insights into the selective response of extraocular muscle layers to denervation and sheds light on some mysterious aspects of human superior oblique palsy.

Purpose.

Although cyclovertical strabismus in humans is frequently attributed to superior oblique (SO) palsy, anatomic effects of SO denervation have not been studied. Magnetic resonance imaging (MRI) and orbital histology was used to study the effects of acute trochlear (CN4) denervation on the monkey SO.

Methods.

Five juvenile macaque monkeys were perfused with formalin for 5 weeks: 15 months after unilateral or bilateral 10-mm intracranial trochlear neurectomy. Denervated and fellow orbits were imaged by MRI, embedded whole in paraffin, serially sectioned at 10-μm thickness, and stained with Masson trichrome. Whole muscle and individual fiber cross sections were quantified in SO muscles throughout the orbit and traced larger fibers in one specimen where they were present.

Results.

MRI demonstrated marked reduction in midorbital cross section in denervated SO muscles, with anterior shift of SO mass preserving overall volume. Muscle fibers exhibited variable atrophy along their lengths. Denervated orbital layer (OL) fiber cross sections were slightly but significantly reduced from control at most anteroposterior locations, but this reduction was much more profound in global layer (GL) fibers. Intraorbital and intramuscular CN4 were uniformly fibrotic. In one animal, there were scattered clusters of markedly hypertrophic GL fibers that exhibited only sparse myomyous junctions only anteriorly.

Conclusions.

CN4 denervation produces predominantly SO GL atrophy with relative OL sparing. Overall midorbital SO atrophy was evident by MRI as early as 5 weeks after denervation, as denervated SO volume shifted anteriorly. Occasional GL fiber hypertrophy suggests that at least some SO fibers extend essentially the full muscle length after trochlear neurectomy.

The cerebellum may monitor motor commands and through internal feedback corrects for anticipated errors. Saccades provide a test of this idea because these movements are completed too quickly for sensory feedback to be useful. Earlier we reported that motor commands that accelerate the eyes toward a constant amplitude target showed variability. Here, we demonstrate that this variability is not random noise, but is due to the cognitive state of the subject. Healthy people showed within saccade compensation for this variability with commands that arrived later in the same saccade. However, in people with cerebellar damage, the same variability resulted in dysmetria. This ability to correct for variability in the motor commands that initiated a saccade was a predictor of each subject’s ability to learn from endpoint errors. In a paradigm in which a target on the horizontal meridian jumped vertically during the saccade (resulting in an endpoint error), the adaptive response exhibited two timescales: a fast timescale that learned quickly from endpoint error but had poor retention, and a slow timescale that learned slowly but had strong retention. With cortical cerebellar damage, the fast timescale of adaptation was effectively absent, but the slow timescale was less impaired. Therefore the cerebellum corrects for variability in the motor commands that initiate saccades within the same movement via an adaptive response that not only exhibits strong sensitivity to previous endpoint errors, but also rapid forgetting.

Background

The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts.

Methodology/Principal Findings

We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions of previous models of the tVOR, none of which could account for our experimental findings.

Conclusions/ Significance

Our results provide new and important information regarding the neural control of the tVOR. Specifically, they point to a key role for the cerebellar nodulus and uvula in the mathematical integration of afferent linear head acceleration signals. This function is likely to be critical not only for the tVOR but also for the otolith-mediated reflexes that control posture and balance.

Purpose

This paper focuses on motor learning within the saccadic and vestibulo-ocular reflex (VOR) oculomotor systems, vital for our understanding how the brain keeps these subsystems calibrated in the presence of disease, trauma, and the changes that invariably accompany normal development and aging. We will concentrate on new information related to multiple time scales of saccade motor learning, adaptation of the VOR during high-velocity impulses, and the role of saccades in VOR adaptation. The role of the cerebellum in both systems is considered.

Methods

Review of data involving saccade and VOR motor learning.

Results

Data supports learning within the saccadic and VOR oculomotor systems is influenced by 1). Multiple time scales, with different rates of both learning and forgetting (seconds, minutes, hours, days, and months). In the case of forgetting, relearning on a similar task may be faster. 2). Pattern of training, learning and forgetting are not similarly achieved. Different contexts require different motor behaviors and rest periods between training sessions can be important for memory consolidation.

Conclusions

The central nervous system has the difficult task of determining where blame resides when motor performance is impaired (the credit assignment problem). Saccade and VOR motor learning takes place at multiple levels within the nervous system, from alterations in ion channel and membrane properties on single neurons, to more complex changes in neural circuit behavior and higher-level cognitive processes including prediction.

Saccadic eye movements rapidly orient the line of sight towards the object of interest. Pre-motor burst neurons (BNs) controlling saccades receive excitation from superior colliculus and cerebellum, but inhibition by omnipause neurons (OPNs) prevents saccades. When the OPNs pause, BNs begin to fire. It has been presumed that part of the BN burst comes from post-inhibitory rebound (PIR). We hypothesized that in the absence of prior inhibition from OPNs there would be no PIR, and thus the increase in initial firing rate of BNs would be reduced. Consequently, saccade acceleration would be reduced. We measured eye movements and showed that sustained eye closure, which inhibits the activity of OPNs and thus hypothetically should weaken PIR, reduced the peak velocity, acceleration, and deceleration of saccades in healthy human subjects. Saccades under closed eyelids also had irregular trajectories; the frequency of the oscillations underlying this irregularity was similar to that of high-frequency ocular flutter (back-to-back saccades) often seen in normal subjects during attempted fixation at straight ahead while eyes are closed. Saccades and quick phases of nystagmus are generated by the same pre-motor neurons, and we found that the quick-phase velocity of nystagmus was also reduced by lid closure. These changes were not due to a mechanical hindrance to the eyes, because lid closure did not affect the peak velocities or accelerations of the eyes in the “slow-phase” response to rapid head movements of comparable speeds to those of saccades. These results indicate a role for OPNs in generating the abrupt onset and high velocities of saccades. We hypothesize that the mechanism involved is PIR in pre-motor burst neurons.

Background

Intestinal malrotation in neonates or infants may require urgent surgical treatment, especially when volvulus and vascular compromise of the midgut are suspected. Successful laparoscopic management of malrotation has been described in a number of case reports. It remains unclear, however, whether laparoscopy for the treatment of malrotation has a success rate equal to that of open surgery and what relative risks exist in terms of conversion and redo surgery in larger numbers of patients. This report describes a retrospective analysis of the clinical outcome for 45 children who underwent laparoscopic treatment of intestinal malrotation at the authors’ institution.

Methods

The 45 patients in this series, ages several days to 13 years, underwent a diagnostic laparoscopy for suspected intestinal malrotation. For 37 patients, malrotation with or without volvulus was diagnosed. All these patients underwent laparoscopic derotation and Ladd’s procedure.

Results

Successful laparoscopic treatment of intestinal malrotation could be performed in 75% of the cases (n = 28), and conversion to an open procedure was necessary in 25% of the cases (n = 9). The median hospital stay was 11 days (range, 2–60 days). Postoperative clinical relapse due to recurrence of malrotation, volvulus, or both occurred for 19% of the laparoscopically treated patients (n = 7). These patients underwent laparoscopic (n = 1) or open (n = 6) redo surgery.

Conclusion

Diagnostic laparoscopy is the procedure of choice when intestinal malrotation is suspected. If present, malrotation can be treated adequately with laparoscopic surgery in the majority of cases. Nevertheless, to prevent recurrence of malrotation or volvulus, a low threshold for conversion to an open procedure is mandated.

The inferior olivary nuclei clearly play a role in creating oculopalatal tremor, but the exact mechanism is unknown. Oculopalatal tremor develops some time after a lesion in the brain that interrupts inhibition of the inferior olive by the deep cerebellar nuclei. Over time the inferior olive gradually becomes hypertrophic and its neurons enlarge developing abnormal soma-somatic gap junctions. However, results from several experimental studies have confounded the issue because they seem inconsistent with a role for the inferior olive in oculopalatal tremor, or because they ascribe the tremor to other brain areas. Here we look at 3D binocular eye movements in 15 oculopalatal tremor patients and compare their behaviour to the output of our recent mathematical model of oculopalatal tremor. This model has two mechanisms that interact to create oculopalatal tremor: an oscillator in the inferior olive and a modulator in the cerebellum. Here we show that this dual mechanism model can reproduce the basic features of oculopalatal tremor and plausibly refute the confounding experimental results. Oscillations in all patients and simulations were aperiodic, with a complicated frequency spectrum showing dominant components from 1 to 3 Hz. The model’s synchronized inferior olive output was too small to induce noticeable ocular oscillations, requiring amplification by the cerebellar cortex. Simulations show that reducing the influence of the cerebellar cortex on the oculomotor pathway reduces the amplitude of ocular tremor, makes it more periodic and pulse-like, but leaves its frequency unchanged. Reducing the coupling among cells in the inferior olive decreases the oscillation’s amplitude until they stop (at ∼20% of full coupling strength), but does not change their frequency. The dual-mechanism model accounts for many of the properties of oculopalatal tremor. Simulations suggest that drug therapies designed to reduce electrotonic coupling within the inferior olive or reduce the disinhibition of the cerebellar cortex on the deep cerebellar nuclei could treat oculopalatal tremor. We conclude that oculopalatal tremor oscillations originate in the hypertrophic inferior olive and are amplified by learning in the cerebellum.