Ionic Direct Current Modulation for Combined Inhibition/Excitation of the Vestibular System.

OBJECTIVE: Prosthetic electrical stimulation delivered to the vestibular nerve could provide therapy for people suffering from bilateral vestibular dysfunction. Common encoding methods use pulse-frequency modulation (PFM) to stimulate the semicircular canals of the vestibular system. We previously showed that delivery of ionic direct current (iDC) can also modulate the vestibular system. In this study, we compare the dynamic range of head velocity encoding from iDC modulation to that of PFM controls. METHODS: Gentamicin-treated wild-type chinchillas were implanted with microcatheter tubes that delivered ionic current to the left ear vestibular canals and stimulated with steps of anodic/cathodic iDC or PFM. Evoked vestibulo-ocular reflex eye velocity was used to compare PFM and iDC vestibular modulation. RESULTS: Cathodic iDC steps effectively elicited eye rotations consistent with an increased firing rate of the implanted semicircular canal afferents. Anodic iDC current steps elicited eye rotations in the opposite direction that, when paired with an adapted cathodic offset, increased the dynamic range of eye rotation velocities in comparison to PFM controls. CONCLUSION: Our results suggest that iDC modulation can effectively modulate the vestibular system across a functional range of rotation vectors and velocities, with a potential benefit over a PFM stimulation paradigm. SIGNIFICANCE: In conjunction with a safe dc delivery system, iDC modulation could potentially increase the range of simulated head rotation velocities available to neuroelectric vestibular prostheses.

Corregistro de la actividad eléctrica cerebral y oculomotora: una alternativa para la investigación en dislexia / Simultaneous recording of electrical brain activity and eye movements: an alternative for research into dyslexia

La dislexia es uno de los trastornos del desarrollo más comunes en la etapa escolar y afecta aproximadamente del 5 a 15% de la población. La comprensión en «tiempo real» de un texto requiere del procesamiento de la información visual entrante a través de una compleja serie de fijaciones cortas de la mirada y movimientos sacádicos de los ojos, así como de la recuperación, actualización e integración de los elementos almacenados en la memoria. Esto ha provocado que numerosas investigaciones hayan hecho un gran uso de 2 métodos en particular para su estudio: los potenciales cerebrales relacionados a eventos (PRE) y el rastreo ocular (RO). Sin embargo, los resultados todavía son muy variables y, por tanto, el origen de la dislexia, desde el punto de vista neurobiológico, continúa siendo aún un tema muy debatido. En este trabajo se realiza una revisión exhaustiva de la literatura donde se abordan los hallazgos de los diferentes estudios neurofisiológicos publicados en el tema, así como sus limitaciones. Luego se analiza la factibilidad del registro simultáneo de la actividad eléctrica cerebral y los movimientos oculares mediante la revisión detallada de los aspectos metodológicos a considerar. Por último, se fundamentan las posibles ventajas de este enfoque para los estudios de la lectura, así como sus aplicaciones potenciales en la investigación en dislexia (AU)

Dyslexia is one of the most common developmental disorders at school age and affects approximately 5-15% of the population. Reading is a complex cognitive task and its comprehension requires the processing of visual input across a complex series of brief fixation pauses and saccadic eye movements, as well as retrieving, updating, and integrating contents of memory. This has led to current research making heavy use of two methods: recording eye movement (EMs) and event-related brain potentials (ERPs). However, results are still equivocal, and therefore, the neurobiology of dyslexia remains hotly debated. This paper presents a comprehensive review of the literature in which the findings of different neurophysiological studies published on the subject are addressed, as well as their limitations. The feasibility of simultaneously recording electrical brain activity and eye movements is then analysed by a detailed review of methodological challenges to consider. Finally, the possible benefits of this approach to reading studies and its potential applications in research into dyslexia are described (AU)

THE EFFECT OF GAZE ANGLE ON THE EVALUATIONS OF SAR AND TEMPERATURE RISE IN HUMAN EYE UNDER PLANE-WAVE EXPOSURES FROM 0.9 TO 10 GHZ.

This article investigates the effect of gaze angle on the specific absorption rate (SAR) and temperature rise in human eye under electromagnetic exposures from 0.9 to 10 GHz. Eye models in different gaze angles are developed based on biometric data. The spatial-average SARs in eyes are investigated using the finite-difference time-domain method, and the corresponding maximum temperature rises in lens are calculated by the finite-difference method. It is found that the changes in the gaze angle produce a maximum variation of 35, 12 and 20 % in the eye-averaged SAR, peak 10 g average SAR and temperature rise, respectively. Results also reveal that the eye-averaged SAR is more sensitive to the changes in the gaze angle than peak 10 g average SAR, especially at higher frequencies.

Supranuclear eye movement abnormalities.

PURPOSE OF REVIEW: The components of the efferent ocular motor network include supranuclear, nuclear, internuclear, infranuclear, neuromuscular junction, and muscle. Within this schema, clinicians are often least acquainted with the supranuclear components; however, derangement of this system is a common cause of ocular dysmotility and diplopia. This article will provide the neurologist with an overview of the anatomy and clinical aspects of the supranuclear ocular motor control systems. RECENT FINDINGS: Continued research moves us toward a more complete understanding of the anatomy and physiology of the complex networks providing supranuclear control of eye movements. This background serves as a framework for the application of clinical techniques, such as bedside assessment of the vestibuloocular reflex, localizing limitations of conjugate gaze (eg, midbrain lesions affecting vertical gaze), and derangements of specific classes of eye movements (pursuit and saccadic dissociation in conditions such as Parinaud dorsal midbrain syndrome). SUMMARY: The efferent neuro-ophthalmic system is a complex series of networks that function to provide accurate control of eye movements, visual stabilization, and ocular alignment. Disturbance within these networks can produce diplopia; impaired control of eye movement, such as gaze palsy; or unwanted eye movements, such as nystagmus.

Effects of acute nicotine on brain function in healthy smokers and non-smokers: estimation of inter-individual response heterogeneity.

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of nicotine effects on antisaccades (an oculomotor measure of the conflict between a reflexive response and a spatially complex volitional response) and prosaccades (involving reflexive overt attentional shifts). Given the known inter-individual variability in drug response we aimed to identify oculomotor variables and brain areas in which significant inter-individual heterogeneity in response to nicotine is observed. To do so we calculated within-session intraclass correlation (ICC) coefficients over measurements obtained before and after nicotine/placebo administration and reasoned that a significant reduction in ICC with nicotine compared to placebo would reflect the operation of significant inter-individual response heterogeneity. Thirteen light-to-moderate smokers and 11 non-smokers completed fMRI during antisaccades before and after subcutaneous injection of 12 microg/kg nicotine or saline placebo in a double-blind, randomised, cross-over design. All participants were healthy, right-handed males. Nicotine and placebo were given on separate occasions approximately 1 week apart with time of injection kept constant. Nicotine significantly reduced antisaccade latencies in both groups. At the level of brain function, during antisaccades the blood oxygen level dependent (BOLD) response in the left frontal eye field was non-significantly reduced by nicotine while it significantly increased following placebo in non-smokers, but there was no discernible effect in smokers. During prosaccades, it was found that deactivation areas (posterior cingulate gyrus and precuneus; right superior temporal gyrus) showed enhanced deactivations following nicotine administration in both groups. ICC analysis identified significant inter-individual response heterogeneity in antisaccade reflexive errors in smokers, and in a number of brain regions, particularly in non-smokers. These findings suggest that nicotine has beneficial effects at the cognitive level and leads to reductions in task-related activations and further decreases of BOLD in deactivation areas. The comparison of within-session ICCs across drug conditions suggests that the effects of nicotine are subject to inter-individual variability at behavioural and neural levels.

Both the hippocampus and striatum are involved in consolidation of motor sequence memory.

Functional magnetic resonance imaging (fMRI) was used to investigate the cerebral correlates of motor sequence memory consolidation. Participants were scanned while training on an implicit oculomotor sequence learning task and during a single testing session taking place 30 min, 5 hr, or 24 hr later. During training, responses observed in hippocampus and striatum were linearly related to the gain in performance observed overnight, but not over the day. Responses in both structures were significantly larger at 24 hr than at 30 min or 5 hr. Additionally, the competitive interaction observed between these structures during training became cooperative overnight. These results stress the importance of both hippocampus and striatum in procedural memory consolidation. Responses in these areas during training seem to condition the overnight memory processing that is associated with a change in their functional interactions. These results show that both structures interact during motor sequence consolidation to optimize subsequent behavior.

The near response: the contributions of Kenji Ohtsuka, MD.

Kenji Ohtsuka, MD and his colleagues at the Sapporo Medical University have investigated the central organization of the near response with anatomical and neurophysiologic studies in cats. Based on their data and clinical observations, they proposed that the rostral pole of the superior colliculus has a critical role in the control of accommodation, vergence, and fixation. Although the central pathways have yet to be fully worked out, the contributions of Dr. Ohtsuka, who died in 2005, have laid an important foundation in the understanding of these functions.

Context-dependent effects of substantia nigra stimulation on eye movements.

In a series of now classic experiments, an output structure of the basal ganglia (BG)--the substantia nigra pars reticulata (SNr)--was shown to be involved in the generation of saccades made in particular behavioral contexts, such as when memory was required for guidance. Recent electrophysiological experiments, however, call this original hypothesis into question. Here we test the hypothesis that the SNr is involved preferentially in nonvisually guided saccades using electrical stimulation. Monkeys performed visually guided and memory-guided saccades to locations throughout the visual field. On 50% of the trials, electrical stimulation of the SNr occurred. Stimulation of the SNr altered the direction, amplitude, latency, and probability of saccades. Visually guided saccades tended to be rotated toward the field contralateral to the side of stimulation, whereas memory-guided saccades tended to be rotated toward the hemifield ipsilateral to the side of stimulation. Overall, the changes in saccade vector direction were larger for memory-guided than for visually guided saccades. Both memory- and visually guided saccades were hypometric during stimulation trials, but the stimulation preferentially affected the length of memory-guided saccades. Electrical stimulation of the SNr produced decreases in visually guided saccades bilaterally. In contrast, memory-guided saccades often had increases in saccade latency bilaterally. Finally, we found approximately 10% reduction in the probability of memory-guided saccades bilaterally. Visually guided saccade probability was unaltered. Taken together the results are consistent with the hypothesis that SNr primarily influences nonvisually guided saccades. The pattern of stimulation effects suggests that SNr influence is widespread, altering the pattern of activity bilaterally across the superior colliculus map of saccades.

Three-dimensional kinematics at the level of the oculomotor plant.

Motor systems often require that superfluous degrees of freedom be constrained. For the oculomotor system, a redundancy in the degrees of freedom occurs during visually guided eye movements and is solved by implementing Listing's law and the half-angle rule, kinematic constraints that limit the range of eye positions and angular velocities used by the eyes. These constraints have been attributed either to neurally generated commands or to the physical mechanics of the eye and its surrounding muscles and tissues (i.e., the ocular plant). To directly test whether the ocular plant implements the half-angle rule, critical to the maintenance of Listing's law, we microstimulated the abducens nerve with the eye at different initial vertical eye positions. We report that the electrically evoked eye velocity exhibits the same eye position dependence as seen in visually guided smooth-pursuit eye movements. These results support an important role for the ocular plant in providing a solution to the degrees-of-freedom problem during eye movements.

Head movement evoked by electrical stimulation in the supplementary eye field of the rhesus monkey.

Although the supplementary eye field (SEF) has been implicated in the control of head movements associated with gaze shifts, there is no direct evidence that SEF plays a role in the generation of head movements independent of gaze. If the SEF does, varying the duration of stimulation should selectively alter the head-movement kinematics during the postgaze-shift period. The duration of the stimulation was manipulated while head-unrestrained monkeys maintained stable head forward postures. The initial positions of the eyes in the orbits were systematically varied. Although combined movements of the eyes and head were produced in the majority of the trials, head movements were sometimes evoked in the absence of gaze shifts. These head-alone movements were most frequent when the initial eye position was contralateral to the stimulated side. When the stimulation produced eye and head movements, gaze onset was sometimes preceded by a relatively low-velocity phase of the head movement. Evoked head movements were primarily horizontal, unlike the gaze shifts, which typically had vertical components that varied according to the initial positions of the eyes in the orbits. The postgaze-shift head movements tended to be of low velocity and in many cases persisted until stimulation offset. In general, prolonging the stimulation resulted in improved centering of the eyes in the orbits. These findings suggest that, in addition to its previously described role in the generation of coordinated eye-head gaze shifts, the SEF is also involved in the control of head movements in the absence of a change of gaze.

Discharge properties of MST neurons that project to the frontal pursuit area in macaque monkeys.

We have used antidromic activation to determine the functional discharge properties of neurons that project to the frontal pursuit area (FPA) from the medial-superior temporal visual area (MST). In awake rhesus monkeys, MST neurons were considered to be activated antidromically if they emitted action potentials at fixed, short latencies after stimulation in the FPA and if the activation passed the collision test. Antidromically activated neurons (n = 37) and a sample of the overall population of MST neurons (n = 110) then were studied during pursuit eye movements across a dark background and during laminar motion of a large random-dot texture and optic flow expansion and contraction during fixation. Antidromically activated neurons showed direction tuning during pursuit (25/37), during laminar image motion (21/37), or both (16/37). Of 27 neurons tested with optic flow stimuli, 14 showed tuning for optic flow expansion (n = 10) or contraction (n = 4). There were no statistically significant differences in the response properties of the antidromically activated and control samples. Preferred directions for pursuit and laminar image motion did not show any statistically significant biases, and the preferred directions for eye versus image motion in each sample tended to be equally divided between aligned and opposed. There were small differences between the control and antidromically activated populations in preferred speeds for laminar motion and optic flow; these might have reached statistical significance with larger samples of antidromically activated neurons. We conclude that the population of MST neurons projecting to the FPA is highly diverse and quite similar to the general population of neurons in MST.

Cingulate cortical cells projecting to monkey frontal eye field and primary motor cortex.

We compared the distribution of cingulate cortical cells projecting to the frontal eye field (FEF) and primary motor cortex (MI) using a multiple retrograde labeling technique. Two fluorescent tracers were injected into physiologically identified FEF and MI in each monkey. The location of cells projecting to the forelimb area of MI served to identify the rostral (CMAr) and caudal (CMAc) cingulate motor areas. We found two foci of cells projecting to the FEF: rostral (CEFr) and caudal (CEFc) cingulate eye field. The CEFr was located rostral to the CMAr, while the CEFc was located rostro-ventral to the CMAc. Cells projecting to the FEF and MI scarcely overlapped, indicating that each area receives different sets of information from the cingulate cortex.

Convergence eye movements evoked by microstimulation of the rostral superior colliculus in the cat.

Results of our previous studies suggest that the circumscribed area in the rostral superior colliculus (SC) of the cat is involved in the control of accommodation. Accommodation is closely linked with vergence eye movements. In this study, we investigated whether or not vergence eye movements are evoked by microstimulation of the rostral SC in the cat. In addition, we studied the effect of chemical inhibition of the rostral SC on visually guided vergence eye movements. This study was conducted on three cats, weighing 2.5-3.5 kg. The animals were trained to carry out visually guided saccade and convergence tasks. Eye movements were measured using search coils placed on both eyes. We recorded eye movements evoked by microstimulation of the rostral SC in the alert cats. Muscimol was injected into the rostral SC, and the effect of SC inactivation on visually guided vergence eye movements was investigated. Convergence eye movements were evoked by low-current stimulation (< 30 microA) of a circumscribed area in the intermediate layers of the rostral SC on one side. Spontaneous saccades were interrupted by the stimulation of the low-threshold area for evoking convergence. Visually guided convergence eye movements were severely diminished by the injection of muscimol into the low-threshold area for evoking convergence of the SC. The rostral SC is related to the control of vergence eye movements as well as accommodation. The rostral SC may be involved in the functional linkage between accommodation, convergence and visual fixation.

Sensorimotor integration in the precentral gyrus: polysensory neurons and defensive movements.

The precentral gyrus of monkeys contains a polysensory zone in which the neurons respond to tactile, visual, and sometimes auditory stimuli. The tactile receptive fields of the polysensory neurons are usually on the face, arms, or upper torso, and the visual and auditory receptive fields are usually confined to the space near the tactile receptive fields, within about 30 cm of the body. Electrical stimulation of this polysensory zone, even in anesthetized animals, evokes a specific set of movements. The movements resemble those typically used to defend the body from objects that are near, approaching, or touching the skin. In the present study, to determine whether the stimulation-evoked movements represent a normal set of defensive movements, we tested whether they include a distinctive, nonsaccadic, centering movement of the eyes that occurs during defensive reactions. We report that this centering movement of the eyes is evoked by stimulation of sites in the polysensory zone. We also recorded the activity of neurons in the polysensory zone while the monkey made defensive reactions to an air puff on the face. The neurons became active during the defensive movement, and the magnitude of this activity was correlated with the magnitude of the defensive reaction. These results support the hypothesis that the polysensory zone in the precentral gyrus contributes to the control of defensive movements. More generally, the results support the view that the precentral gyrus can control movement at the level of complex sensorimotor tasks.

Effect of source intensity on ability to fixate: implications for laser safety.

During long-term viewing of a continuous light source, head and eye movements affect the distribution of energy deposited in the retina. Previous studies of eye movements during a fixation task provided data used for revising the safety limits for long-term viewing of such sources. These studies have been continued to determine the effect of source brightness on the nature of fixational eye movements. Volunteers fixated for 50 s on a HeNe laser (lambda = 632.8 nm) masked by a small aperture to produce a target subtending approximately 0.03 mrad in the visual field. The source was attenuated to yield corneal irradiance values in the range 0.6 pW cm(-2) to 6 microW cm(-2). Eye movements were recorded using a Dual Purkinje Image Eyetracker. The data were characterized by fixation ellipses that represent areas of the retina in which the image of the spot was located 68% of the time of each trial. Significant variation across subjects in the tightness of fixation was observed. Over the eight orders of magnitude of source brightness used in this experiment (10(-13) to 10(-6) W cm(-2)), no subject showed more than roughly a factor of two variation in the area of the fixation ellipse. No statistically significant trend in tightness of fixation as a function of source brightness was observed. There was no loss of ability to fixate, nor any drive to aversion, at the higher source intensities.

Defining and quantifying the social phenotype in autism.

OBJECTIVE: Genetic and neurofunctional research in autism has highlighted the need for improved characterization of the core social disorder defining the broad spectrum of syndrome manifestations. METHOD: This article reviews the advantages and limitations of current methods for the refinement and quantification of this highly heterogeneous social phenotype. RESULTS: The study of social visual pursuit by use of eye-tracking technology is offered as a paradigm for novel tools incorporating these requirements and as a research effort that builds on the emerging synergy of different branches of social neuroscience. CONCLUSIONS: Advances in the area will require increased consideration of processes underlying experimental results and a closer approximation of experimental methods to the naturalistic demands inherent in real-life social situations.

[Retrobulbar irradiation for Graves' ophthalmopathy -- long-term results]. / Retrobulbäre Bestrahlung bei endokriner Orbitopathie -- Erfahrungen im Langzeitverlauf.

BACKGROUND: Significance of retrobulbar irradiation in patients suffering form Graves' ophthalmopathy, though established since almost one century, is subject of scientific debate. The present study investigated the effect of retrobulbar irradiation using a standardized protocol focussing on long term results. PATIENTS AND METHODS: Between 1981 and 1997, 104 patients treated by retrobulbar irradiation (10 to 20 Gray) due to Graves' disease. Twenty-nine of these underwent irradiation as sole treatment (mean follow-up 57 months), while in the remaining 75, it was combined with a systemic steroid treatment (mean follow-up 40 months). Patients were evaluated regarding proptosis, intraocular pressure, lid signs, motility as well as subjective assessment of double vision and retrobulbar pain. RESULTS: While proptosis remained unchanged, lid signs, chemosis and intraocular pressure showed slight and statistically significant improvement. However, these findings were considered to be clinically insignificant. Retrobulbar pain was improved in 75 % of patients. 25 % of patients showed improved motility, 75 % remained stable, and in none of them was there a deterioration of ductions. Results proved stable even in long-term follow-up. 25 % per cent of patients underwent a surgical procedure one year after radiotherapy. CONCLUSIONS: In our series, we could not demonstrate an additional benefit of systemic steroids when combined with retrobulbar irradiation. Up to sixteen years after treatment, no treatment-related adverse reaction was seen. We found a remarkable improvement in ocular motility. This holds even more true in comparison to the natural course of the condition. Retrobulbar irradiation seems to shorten the duration of the disease, thus allowing earlier performance of eventual rehabilitative surgery.

Arteriovenous malformation animal model for radiosurgery: the rete mirabile.

PURPOSE: To study the effects of single-dose radiation on the porcine rete mirabile, a tangle of microvessels that mimics human arteriovenous malformations of the brain. METHODS: Eight retia mirabilia received a single dose of radiation under stereotactic location with digital angiography and CT. The following doses were applied: 20, 30, 40, 50, 60, 70, 80, and 90 Gy. The animals were followed up for a period of 7 months. Findings at neurologic examination, serial angiography, and histopathologic examination were analyzed. RESULTS: Progressive occlusion as observed by angiography corresponded to the histopathologic finding of intimal hyperplasia; that is, marked thickening of the vessel wall, progressing to occlusion of the vascular lumen, and associated thrombosis. A direct dose response was noted for these changes. Neurologic findings were related to the dose distribution and to histologic findings in structures adjacent to the rete mirabile. CONCLUSION: The rete mirabile is an excellent model by which to study the radiologic and histologic effects of single-dose radiation to the microvasculature of the central nervous system.