Evidence for three-dimensional cortical control of gaze from epileptic patients.

Electrophysiological studies in primates indicate that the eye fields of the cerebral hemispheres control gaze in three-dimensional space, and contain neurons that encode both conjugate (versive) and vergence eye movements. Two patients with epilepsy who exhibited disconjugate contraversive horizontal eye movements are described, one during electrical stimulation of the frontal eye fields and the other during focal seizures. We postulate that these eye movements resulted from combined contralateral version and vergence, and suggest that human cortical eye fields also govern visual search in a three-dimensional world, shifting the point of fixation between targets lying in different directions and at different depths.

Studying human exposure to vehicular emissions using computational fluid dynamics and an urban mobility simulator: The effect of sidewalk residence time, vehicular technologies and a traffic-calming device.

A computational system consisting of an urban mobility simulator, validated fluid dynamics and an integral exposure model, is proposed to obtain cyclist and pedestrian exposure to PMx and NOx. Pedestrian activities in the urban anthroposphere include walking and running. The computational experiments take place in a computer-generated urban canyon, subject to emissions from diesel and gasoline Euro 5 and Euro 6 vehicular technologies, in continuous and stop-and-go traffic scenarios, and three wind directions at two speeds. The exposure time in the computational domain of slow and fast pedestrians were obtained. Slow pedestrians had exposure times around 17% more than fast pedestrians due to their higher sidewalk residence time. Runners and cyclists decreased their exposures by 57% and 73% respectively compared with walkers. Two traffic scenarios are implemented: one due the presence of a hump and another without a hump. The presence of the hump, increased exposure and fuel consumption by 60% per heavy duty vehicle, about 44-48% per light duty vehicle and about 54-71% per passenger car. Vehicular technology had a large influence on exposure: Heavy duty-Euro 6 vehicle decreased 86% the exposure to PM2.5 and 66% to NOX with respect to Euro 5. The proposed computational system provides information on how wind velocity influenced the inhomogeneous pollutant distribution in the street-canyon, causing exposure to be dependent on pedestrian route location. Microscale sidewalk areas in the order of meters containing higher concentrations were thus located. The cleanest routes in the urban canyon were identified. When the wind intensity doubled from 2 to 4 m s-1, exposure concentration decreased around 45%. The proposed system provides a computational platform to study urban atmospheric fluids, scenarios such as pedestrian routes, vehicular technologies, traffic velocities, meteorological conditions and urban morphology affecting pollution exposure.

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

Ocular stability and set-point adaptation.

A fundamental challenge to the brain is how to prevent intrusive movements when quiet is needed. Unwanted limb movements such as tremor impair fine motor control and unwanted eye drifts such as nystagmus impair vision. A stable platform is also necessary to launch accurate movements. Accordingly, nature has designed control systems with agonist (excitation) and antagonist (inhibition) muscle pairs functioning in push-pull, around a steady level of balanced tonic activity, the set-point Sensory information can be organized similarly, as in the vestibulo-ocular reflex, which generates eye movements that compensate for head movements. The semicircular canals, working in coplanar pairs, one in each labyrinth, are reciprocally excited and inhibited as they transduce head rotations. The relative change in activity is relayed to the vestibular nuclei, which operate around a set-point of stable balanced activity. When a pathological imbalance occurs, producing unwanted nystagmus without head movement, an adaptive mechanism restores the proper set-point and eliminates the nystagmus. Here we used 90 min of continuous 7 T magnetic field labyrinthine stimulation (MVS) in normal humans to produce sustained nystagmus simulating vestibular imbalance. We identified multiple time-scale processes towards a new zero set-point showing that MVS is an excellent paradigm to investigate the neurobiology of set-point adaptation.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'.

Ranking current and prospective NO2 pollution mitigation strategies: An environmental and economic modelling investigation in Oxford Street, London.

Air pollution continues to be a problem in the urban environment. A range of different pollutant mitigation strategies that promote dispersion and deposition exist, but there is little evidence with respect to their comparative performance from both an environmental and economic perspective. This paper focuses on examining different NO2 mitigation strategies such as trees, buildings facades coated with photocatalytic paint and solid barriers in Oxford Street in London. The case study findings will support ranking the environmental and economic impacts of these different strategies to improve personal exposure conditions on the footpath and on the road in a real urban street canyon. CFD simulations of airflow and NO2 dispersion in Oxford Street in London were undertaken using the OpenFOAM software platform with the k-ε model, taking into account local prevailing wind conditions. Trees are shown to be the most cost-effective strategy, with a small reduction in NO2 concentrations of up to 0.7% on the road. However, solid barriers with and without the application of photocatalytic paint and an innovative material (20 times more expensive than trees) can improve air quality on the footpaths more substantially, up to 7.4%, yet this has a significant detrimental impact on NO2 concentrations (≤23.8%) on the road. Photocatalytic paint on building surfaces presented a minimal environmental reductions (1.2%) and economic (>100 times more expensive than trees) mitigation strategy. The findings recognised the differences between footpath and road concentrations occurred and that a focused examination of three pollution hotspots can provide more cost effective pollution mitigation. This study considers how a number of pollutant mitigation measures can be applied in a single street canyon and demonstrates the strengths and weaknesses of these strategies from economic and environmental perspectives. Further research is required to extrapolate the findings presented here to different street geometries.

Tenotomy does not affect saccadic velocities: support for the "small-signal" gain hypothesis.

We investigated the effects of four-muscle tenotomy on saccadic characteristics in infantile nystagmus syndrome (INS) and acquired pendular nystagmus (APN). Eye movements of 10 subjects with INS and one with APN were recorded using infrared reflection, magnetic search coil, or high-speed digital video. The expanded nystagmus acuity function (NAFX) quantified tenotomy-induced foveation changes in the INS. Saccadic characteristics and peak-to-peak nystagmus amplitudes were measured. Novel statistical tests were performed on the saccadic data. Six out of the 10 INS subjects showed no changes in saccadic duration, peak velocity, acceleration, or trajectory. In the other four, the differences were less than in peak-to-peak amplitudes (from 14.6% to 39.5%) and NAFX (from 22.2% to 162.4%). The APN subject also showed no changes despite a 50% decrease in peak-to-peak amplitude and a 34% increase in NAFX. The "small-signal" changes (peak-to-peak nystagmus amplitude and NAFX) were found to far exceed any "large-signal" changes (saccadic). Tenotomy successfully reduced INS and APN, enabling higher visual acuity without adversely affecting saccadic characteristics. These findings support the peripheral, small-signal gain reduction (via proprioceptive tension control) hypothesis. Current linear plant models, limited to normal steady-state muscle tension levels, cannot explain the effects of the tenotomy.

Evaluating large saccades in patients with brain-stem or cerebellar disorders.

Clinicians conventionally test saccades at the bedside by noting the accuracy, initiation time, and speed of large movements, with the patient's head stationary. Partly for methodological reasons, laboratory analysis of saccades has mainly focused on movements of 20 degrees or less. By measuring the velocity waveform of large saccades, it is possible to examine more closely the way in which brain stem and cerebellum guide the eye to the target. Large saccades made by healthy humans show a positively skewed velocity profile. Slow saccades made by patients with brain-stem disorders show a prolonged plateau of low velocity. Some patients with cerebellar disorders may show increased acceleration and deceleration of saccades. Each of these velocity waveforms can be modeled by changing the parameters that describe medium-lead burst neuron firing. In certain other brain-stem and cerebellar disorders, transient decelerations or premature terminations of saccades occur; such velocity waveforms cannot be modeled solely by changing the parameters that describe burst neuron firing. Instead, it is necessary to postulate dysfunction of the mechanism that normally inhibits pontine omnipause neurons, thereby permitting burst neurons to discharge until the saccade is completed. Analysis of large, abnormal saccades calls for application of novel techniques to identify the beginning and end of the saccadic pulse command.

Rapid regular respiration in unconscious patients.

Respiratory frequency has been studied by strain gauge and impedance pneumography in a group of unconscious patients suffering from a variety of medical conditions, and has been compared with breathing in control subjects during wakefulness and sleep. Seventeen of 25 comatose patients had breathing patterns amenable to computerized statistical analysis of respiratory rate which demonstrated abnormalities in all patients studied. Unconscious patients breathed more rapidly and regularly than controls. Rapidity of respiration was not consistently associated with any specific central nervous system lesion, and was usually accompanied by coexistent pulmonary disease. Increasing regularity of respiration correlated well with deepening of coma and accurately reflected ultimate outcome even when other clinical signs were unchanging.

Lateral deviation of the eyes on forced lid closure in patients with cerebral lesions.

We examined 35 patients with unilateral cerebral lesions to determine the incidence of lateral deviation of the eyes under forcefully closed lids and the reliability of this sign in predicting the side of the lesion. Only patients with radiologically confirmed unilateral lesions were studied. Over 70% of patients had contralateral ocular deviation (Cogan's "spasticity of conjugate gaze"), 20% had ipsilateral deviation, and less than 9% of the patients had no deviation. Lateral ocular deviation was as sensitive, but not as specific, as a unilateral Babinski plantar response in determining the side with the lesion. Contralateral deviation was more common with parietotemporal localization, suggesting that the phenomenon reflects an underlying disturbance of attentional mechanisms.

Pendular nystagmus in patients with peroxisomal assembly disorder.

BACKGROUND: Pendular nystagmus commonly occurs in congenital and acquired disorders of myelin. OBJECTIVE: To characterize the nystagmus in 3 siblings with an infantile form of an autosomal recessive peroxisomal assembly disorder causing leukodystrophy. DESIGN: We examined visual function and measured eye movements using infrared oculography. We noted changes in eye speed and frequency before and after the administration of gabapentin to 1 patient. RESULTS: All 3 siblings showed optic atrophy and pendular nystagmus that was predominantly horizontal, at a frequency of 3 to 6 Hz, with phase shifts of 45 degrees to 80 degrees between the oscillations of each eye. Gabapentin administered to 1 child caused a modest improvement of vision and the reduction of the velocity and frequency of oscillations in the eye with worse nystagmus. CONCLUSION: The pendular nystagmus in these patients was due to their leukodystrophy and may have a similar pathogenesis to the oscillations seen in other disorders affecting central myelin.

A reevaluation of the vestibulo-ocular reflex: new ideas of its purpose, properties, neural substrate, and disorders.

Conventional views of the vestibulo-ocular reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved--locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (< 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome).

A hypothetical scheme for the brainstem control of vertical gaze.

OBJECTIVES: To develop a hypothetical scheme to account for clinical disorders of vertical gaze based on recent insights gained from experimental studies. METHODS: The authors critically reviewed reports of anatomy, physiology, and effects of pharmacologic inactivation of midbrain nuclei. RESULTS: Vertical saccades are generated by burst neurons lying in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Each burst neuron projects to motoneurons in a manner such that the eyes are tightly coordinated (yoked) during vertical saccades. Saccadic innervation from riMLF is unilateral to depressor muscles but bilateral to elevator muscles, with axons crossing within the oculomotor nucleus. Thus, riMLF lesions cause conjugate saccadic palsies that are usually either complete or selectively downward. Each riMLF contains burst neurons for both up and down saccades, but only for ipsilateral torsional saccades. Therefore, unilateral riMLF lesions can be detected at the bedside if torsional quick phases are absent during ipsidirectional head rotations in roll. The interstitial nucleus of Cajal (INC) is important for holding the eye in eccentric gaze after a vertical saccade and coordinating eye-head movements in roll. Bilateral INC lesions limit the range of vertical gaze. The posterior commissure (PC) is the route by which INC projects to ocular motoneurons. Inactivation of PC causes vertical gaze-evoked nystagmus, but destructive lesions cause a more profound defect of vertical gaze, probably due to involvement of the nucleus of the PC. Vestibular signals originating from each of the vertical labyrinthine canals ascend to the midbrain through several distinct pathways; normal vestibular function is best tested by rotating the patient's head in the planes of these canals. CONCLUSIONS: Predictions of a current scheme to account for vertical gaze palsy can be tested at the bedside with systematic examination of each functional class of eye movements.

The syndrome of 'pure akinesia' and its relationship to progressive supranuclear palsy.

Five patients developed a stereotyped syndrome of progressive akinesia of gait, speech, and hand-writing without rigidity, tremor, or dementia. The symptoms did not improve with levodopa. These clinical findings conform to a syndrome described repeatedly in Japan since 1974 as "pure akinesia." Evidence has indicated that pure akinesia often represents a pre-ocular motor, and in some cases an ocular motor-sparing, form of progressive supranuclear palsy (PSP). Although we found disorders of eyelid movements, none of the patients demonstrated a gaze palsy on clinical examination. Four patients underwent eye movement recordings. The two patients with the longest disease duration had slow or small vertical saccades. These findings support the notion that patients with pure akinesia may develop a vertical gaze palsy, similar to that in PSP, late in their course. Our patients show that pure akinesia occurs in North America as well as in Japan. Recognition of the syndrome of pure akinesia may suggest the diagnosis of PSP before the development of abnormalities of ocular movement.

Epileptic gaze deviation and nystagmus.

We studied a patient with stereotyped focal seizures characterized by leftward conjugate eye- and head-turning followed by nystagmus. Eye deviation was associated with the appearance of seizure activity, recorded over the right temporo-occipital scalp, that did not spread frontally. The initial eye deviation consisted of a staircase of small saccades. The subsequent nystagmus showed rightward decreasing-velocity exponential slow phases and normal leftward quick phases. Saccadic eye movements due to seizures may occur via projections from posterior cortical areas as well as from the frontal eye fields.

The characteristics and mechanisms of visual disturbance associated with anticonvulsant therapy.

Eight epileptic patients receiving anticonvulsants had recurrent visual disturbances in the form of diplopia and oscillopsia in the horizontal or vertical planes. The symptoms could be ascribed to impaired vergence mechanisms, vertical nystagmus, or abnormalities of the vestibulo-ocular reflex. Other eye movements, such as pursuit and gaze-holding, were also affected, but did not lead to complaints. Episodes of visual disturbance were often preceded by prodromes of ocular or systemic discomfort, after which oscillopsia or diplopia evolve rapidly. The symptomatology was stereotyped but unique for each patient and may reflect idiosyncratic susceptibility to the ocular motor side effects of anticonvulsants. Six of the 8 patients were taking carbamazepine and phenytoin in combination, which have similar effects on the ocular motor system.

Maturation of the vestibulo-ocular reflex in normal infants during the first 2 months of life.

We measured the dynamic properties of the vestibulo-ocular reflex (VOR) in 20 healthy, newborn babies, using sinusoidal and velocity-step rotational stimuli. With sinusoidal stimuli, quick phases of nystagmus were uncommon and there was a large phase lead of eye position over head position that exceeded 20 degrees at frequencies below 0.5 Hz. With velocity-step stimuli, primary nystagmus lasted for a mean duration of 10 seconds and was followed by an early reversal phase of nystagmus. By 2 months of age, primary nystagmus induced by velocity-step stimuli was more prolonged (mean duration, 15 seconds) and the reversal phase occurred later. We postulate that these changes reflect maturation of visual pathways essential in calibrating the VOR so that vision remains clear during head perturbations.

Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride.

We conducted a randomized, double-blind, crossover trial of two anticholinergic agents--trihexyphenidyl and tridihexethyl chloride (a quaternary anticholinergic that does not cross the blood-brain barrier)--in patients with acquired nystagmus and measured visual acuity and nystagmus before and at the end of 1 month on each medication. Of the 10 patients admitted to the study, only five completed trials of both drugs due to intolerance of medication or intercurrent illness. Of six patients who completed the trial of trihexyphenidyl, only one showed improvement. Of six patients who completed a trial of tridihexethyl chloride, four showed improvement. We conclude that (1) trihexyphenidyl is not a reliable treatment for acquired nystagmus, although occasional patients may benefit; (2) anticholinergic agents may suppress nystagmus by peripheral rather than central mechanisms; and (3) the side effects of anticholinergic agents limit their effectiveness in the treatment of nystagmus.

Acquired pendular nystagmus in toluene addiction.

We studied the ocular motor abnormalities in 4 patients chronically addicted to sniffing glue containing toluene. They showed acquired pendular nystagmus with horizontal and vertical components. One patient also showed saccadic oscillations. The pendular nystagmus may be a manifestation of a disturbance in brainstem-cerebellar connections secondary to the toxic effect of toluene on white matter.

Hyperactive vestibulo-ocular reflex in cerebellar degeneration: pathogenesis and treatment.

We studied a patient with a cerebellar degeneration and hyperactive vestibulo-ocular reflex (VOR). He complained of oscillopsia and blurred vision with head movement. A twofold increase in VOR gain (peak eye velocity/peak head velocity) at high frequencies was associated with a VOR time constant of 6 seconds (low normal). Visual cancellation ("suppression") of the VOR and smooth pursuit were also abnormal. We hypothesized that his high VOR gain was due to dysfunction of olivocerebellar projections. Physostigmine reduced his VOR gain, consistent with the hypothesis that these projections are cholinergic.