Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery.

PURPOSE: To observe the change in horizontal smooth pursuit in patients with intermittent exotropia before and after strabismus surgery. METHODS: The smooth pursuit of patients with intermittent exotropia was recorded using a video eye-tracker before and 1 week, and 1, 3, and 6 months after strabismus surgery. Subjects were asked to track a step-ramp target moving at ±6.1°/sec horizontally as accurately as possible under binocular viewing. The differences in gain (eye velocity divided by target velocity) and amplitude of smooth pursuit between right and left eyes before and after surgery were compared. RESULTS: A total of 9 patients (mean age, 22.2 ± 13.9 years) were included. Mean preoperative ocular alignment at near was 59.1Δ ± 34.7Δ. The difference in gain between the left and right eyes before surgery was 0.23 ± 0.1; in amplitude, 3.0° ± 3.7°. These values were improved at 1 week after surgery (gain, 0.08 ± 0.06; amplitude, 0.9° ± 0.65°) and continued to improve for 6 months after surgery; however, ocular alignment at near reverted from 5.9Δ ± 10.5Δ to 18.9Δ ± 17.5Δ by 6 months after surgery. CONCLUSIONS: In this small patient cohort, surgical correction of ocular alignment improved binocular coordination of smooth pursuit in intermittent exotropia. In the long term, the improvement of the binocular coordination of smooth pursuit tended to remain, although the eye position partially reverted to the presurgical state.

Effects of nicotine on smooth pursuit eye movements in healthy non-smokers.

RATIONALE: The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies. OBJECTIVES: In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system. METHODS: Healthy adult non-smokers (N = 18 females, N = 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2 Hz, 0.4 Hz, 0.6 Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2 mg nicotine gum. RESULTS: Nicotine increased peak pursuit gain relative to placebo (p < .001), but an interaction with distractor condition (p = .001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p = .01), particularly at higher target frequencies (two-way interaction, p = .04). However, a three-way interaction (p = .006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6 Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures. CONCLUSIONS: Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit.

Neural Plasticity Following Surgical Correction of Strabismus in Monkeys.

Purpose: Although widely practiced, surgical treatment of strabismus has varying levels of success and permanence. In this study we investigated adaptive responses within the brain and the extraocular muscles (EOM) that occur following surgery and therefore determine long-term success of the treatment. Methods: Single cell responses were collected from cells in the oculomotor and abducens nuclei before and after two monkeys (M1, M2) with exotropia (divergent strabismus) underwent a strabismus correction surgery that involved weakening of the lateral rectus (LR) and strengthening of the medial rectus (MR) muscle of one eye. Eye movement and neuronal data were collected for up to 10 months after surgery during a monocular viewing smooth-pursuit task. These data were fit with a first-order equation and resulting coefficients were used to estimate the population neuronal drive (ND) to each EOM of both eyes. Results: Surgery resulted in a ∼70% reduction in strabismus angle in both animals that reverted toward presurgical misalignment by approximately 6 months after treatment. In the first month after surgery, the ND to the treated MR reduced in one animal and ND to the LR increased in the other animal, both indicating active neural plasticity that reduced the effectiveness of the treatment. Adaptive changes in ND to the untreated eye were also identified. Conclusions: Active neural and muscle plasticity corresponding to both the treated and the untreated eye determines longitudinal success following surgical correction of strabismus. Outcome of surgical treatment could be improved by identifying ways to enhance "positive" adaptation and limit "negative" adaptation.

[Screening for reading difficulties in Parkinson's disease: An evaluation of the Alouette test]. / Exploration des troubles de la lecture dans la maladie de Parkinson : utilité du test de l'alouette.

INTRODUCTION: Reading disorders in Parkinson's disease (PD) are poorly evaluated due to the lack of validated tests to screen for them. They are often attributed to hand tremors associated with the disease. In this study, we evaluated the "alouette test" validated for dyslexia screening, in PD by comparing the results to healthy patients. METHODS: The "alouette test" was conducted on a fixed surface to avoid errors related to tremor. A fixation and tracking test were then performed. All the tests were filmed to be analyzed later by 2 examiners blinded to the neurological diagnosis. RESULTS: Thirty-eight patients were included, 19 with PD, and 19 healthy age-matched patients. PD patients read on average 250.9±13.7 words correctly vs. 260.3±2.7 words for healthy patients (P=0.008). This difference was greatest for the older patient subgroup (>65 years), who had the disease longer (P=0.014). Tracking and fixation tests were more impaired in PD patients compared to healthy patients. CONCLUSION: This study highlighted many reading disorders in PD. The use of the "alouette test" which can easily be implemented in clinical practice, could help to diagnose these disorders. Better evaluation of these difficulties would allow for better medical care of these patients.

Caffeine increases the velocity of rapid eye movements in unfatigued humans.

BACKGROUND: Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued. METHODS: Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg·kg-1 body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography. RESULTS: Caffeine was associated with higher peak saccade velocities (472 ± 60° s-1) compared to placebo (455 ± 62° s-1). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine. CONCLUSIONS: These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements.

INTRODUCTION: Nicotine and methylphenidate are putative cognitive enhancers in healthy and patient populations. Although they stimulate different neurotransmitter systems, they have been shown to enhance performance on overlapping measures of attention. So far, there has been no direct comparison of the effects of these two stimulants on behavioural performance or brain function in healthy humans. Here, we directly compare the two compounds using a well-established oculomotor biomarker in order to explore common and distinct behavioural and neural effects. METHODS: Eighty-two healthy male non-smokers performed a smooth pursuit eye movement task while lying in an fMRI scanner. In a between-subjects, double-blind design, subjects either received placebo (placebo patch and capsule), nicotine (7mg nicotine patch and placebo capsule), or methylphenidate (placebo patch and 40mg methylphenidate capsule). RESULTS: There were no significant drug effects on behavioural measures. At the neural level, methylphenidate elicited higher activation in left frontal eye field compared to nicotine, with an intermediate response under placebo. DISCUSSION: The reduced activation of task-related regions under nicotine could be associated with more efficient neural processing, while increased hemodynamic response under methylphenidate is interpretable as enhanced processing of task-relevant networks. Together, these findings suggest dissociable neural effects of these putative cognitive enhancers.

Unaffected smooth pursuit but impaired motion perception in monocularly enucleated observers.

The objective of this paper was to study the characteristics of closed-loop smooth pursuit eye movements of 15 unilaterally eye enucleated individuals and 18 age-matched controls and to compare them to their performance in two tests of motion perception: relative motion and motion coherence. The relative motion test used a brief (150 ms) small stimulus with a continuously present fixation target to preclude pursuit eye movements. The duration of the motion coherence trials was 1s, which allowed a brief pursuit of the stimuli. Smooth pursuit data were obtained with a step-ramp procedure. Controls were tested both monocularly and binocularly. The data showed worse performance by the enucleated observers in the relative motion task but no statistically significant differences in motion coherence between the two groups. On the other hand, the smooth pursuit gain of the enucleated participants was as good as that of controls for whom we found no binocular advantage. The data show that enucleated observers do not exhibit deficits in the afferent or sensory pathways or in the efferent or motor pathways of the steady-state smooth pursuit system even though their visual processing of motion is impaired.

Davida Teller Award Lecture 2013: the importance of prediction and anticipation in the control of smooth pursuit eye movements.

The ability of smooth pursuit eye movements to anticipate the future motion of targets has been known since the pioneering work of Dodge, Travis, and Fox (1930) and Westheimer (1954). This article reviews aspects of anticipatory smooth eye movements, focusing on the roles of the different internal or external cues that initiate anticipatory pursuit.We present new results showing that the anticipatory smooth eye movements evoked by different cues differ substantially, even when the cues are equivalent in the information conveyed about the direction of future target motion. Cues that convey an easily interpretable visualization of the motion path produce faster anticipatory smooth eye movements than the other cues tested, including symbols associated arbitrarily with the path, and the same target motion tested repeatedly over a block of trials. The differences among the cues may be understood within a common predictive framework in which the cues differ in the level of subjective certainty they provide about the future path. Pursuit may be driven by a combined signal in which immediate sensory motion, and the predictions about future motion generated by sets of cues, are weighted according to their respective levels of certainty. Anticipatory smooth eye movements, an overt indicator of expectations and predictions, may not be operating in isolation, but may be part of a global process in which the brain analyzes available cues, formulates predictions, and uses them to control perceptual, motor, and cognitive processes.

Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism.

Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects.

Neural mechanisms for smooth pursuit in strabismus.

The visual and oculomotor systems of primates are immature at birth and sensitive to injury. If synergistic interactions between visual and oculomotor systems are compromised during the first months of life, disorders in eye alignment, gaze holding, and smooth pursuit (SP) follow. Here we consider some potential neural mechanisms supporting SP and associated vestibular ocular reflex (VOR) behavior in normal and strabismic monkeys. Experimental strabismus was created by prism goggle wearing or eye muscle surgery in rhesus monkeys (Macaca mulatta). SP and cancellation of the VOR were highly asymmetric in strabismic monkeys during monocular viewing conditions. Similar asymmetric SP and VOR cancellation could be produced in normal monkeys by delivering unilateral muscimol injections to the dorsolateral pontine nucleus (DLPN). We suggest that failure to develop balanced cortical-brainstem circuits in strabismus accounts for many of the components of infantile strabismus syndrome.

Two cases of improvement of smooth pursuit eye movements after selective posterior rhizotomy.

OBJECTIVE: Selective posterior rhizotomy (SPR) represents a standard neurosurgical approach in the treatment of spasticity in children with cerebral palsy (CP). Beside the reduction of spasticity in lower limbs, SPR may have suprasegmental effects, considerably above the surgery site. In this communication, we report on the improvement of smooth pursuit eye movements (SPEM) in two children after SPR. MATERIAL AND METHODS: Four children with CP underwent SPR. Eye movements were registered by infrared video-oculography before and after the surgery. RESULTS: The analysis of SPEM showed the improvement of the correlation coefficient of the eye response to the stimulus after SPR in two subjects. Improvement of SPEM performance was largely due to suppression of spontaneous fixation nystagmus. CONCLUSION: SPR may lead to the improvement of SPEM in children with CP. The influence of SPEM improvement on quality of life in a group of severely disabled nonambulant children with CP remains to be assessed.

The effect of acute superior oblique palsy on vertical pursuit in monkeys.

PURPOSE: To investigate vertical smooth pursuit eye movements in monkeys with acute acquired superior oblique palsy (SOP). METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys. After surgery, the paretic eye was patched for 6 or 9 days, and then binocular viewing was allowed. Eye movements were measured with binocular, dual search coils, before and after surgery, under monocular viewing conditions. Vertical pursuit movements along the midline were elicited by using triangular-wave (20 deg/s, +/-20 degrees ) or step-ramp (20 deg/s) stimuli at a distance of 66 cm. RESULTS: During the early post-lesion period, before binocular viewing was allowed, pursuit velocity of the paretic eye during triangular-wave tracking was lower than that of the normal eye. When the viewing eye crossed straight ahead, the changes in pursuit velocity conjugacy were similar for upward and downward tracking. After habitual binocular viewing was allowed, differences between upward and downward pursuit emerged. When measured approximately 30 days after lesioning, this directional asymmetry was less during the open-loop period of step-ramp tracking than during triangular-wave tracking. CONCLUSIONS: Rhesus monkeys with acute acquired SOP show characteristic changes in vertical pursuit, with deficits for both upward and downward tracking, and differences between the initiation of step-ramp pursuit and the sustained response during triangular-wave tracking. The habitual viewing condition (monocular versus binocular) also affected the pattern of deficit.

Ophthalmic features of ataxia telangiectasia-like disorder.

INTRODUCTION: Ataxia telangiectasia (AT) is a recessive neurodegenerative disease due to a faulty repair mechanism for breaks in double-stranded DNA (ATM mutation). Ophthalmic features of AT include conjunctival telangiectasia, strabismus, saccadic dysfunction with head thrusts, and convergence insufficiency. Ataxia telangiectasia-like syndrome (ATLD) is a more recently recognized condition due to homozygous mutation in MRE11, a gene also involved in the cellular repair response to double-stranded DNA breaks; ophthalmic features of ATLD are not well described. The purpose of this article is to describe the ophthalmic features of ATLD. METHODS: Full ophthalmologic and orthoptic evaluations were obtained in 13 individuals: 10 previously reported ATLD patients, an additional related ATLD patient, and 3 nonaffected relatives. All individuals were from three unrelated consanguineous Saudi Arabian families harboring an MRE11 mutation (W210C). Age range was from 2 to 40 years of age. RESULTS: No affected patient had structural ocular abnormality (eg, conjunctival telangiectasia), manifest strabismus at distance, or duction limitation. All but one (the youngest) had saccadic dysfunction (without head thrusts). Most patients had abnormal convergence. Older patients had nystagmus with abnormalities in smooth pursuit and vestibular ocular reflex. All patients had cerebellar atrophy by neuroimaging and slowly progressive ataxia. The unaffected heterozygous relatives had unremarkable ophthalmic and neurologic examinations. CONCLUSIONS: Saccadic dysfunction without head thrusts and convergence abnormality are common in ATLD secondary to homozygous W210C MRE11 mutation. Older patients have nystagmus with abnormalities in smooth pursuit and vestibular ocular reflex. Eye movement control systems apparently deteriorate with time in this rare neurological disease. Ophthalmic features of AT that were not observed in any of our ATLD patients include conjunctival telangiectasia, head thrusting, and manifest strabismus at distance.

Square-wave jerks and smooth pursuit impairment as subtle early signs of brain involvement in Langerhans' cell histiocytosis.

Central nervous system (CNS) involvement in Langerhans' cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by motor and cognitive decline. Detailed analysis of ocular motor abnormalities is lacking. We report on a 60-year-old male with histologically confirmed LCH who developed oscillopsia and gait ataxia over a 1-year period. Eye movements recorded with infrared oculography revealed a high rate of square-wave jerks (SWJ) with frequencies of 41 min(-1) on average and amplitudes between 1 degrees and 7 degrees , as well as marked impairment of smooth tracking of sinusoidally moving targets. Furthermore, static posturography disclosed increased body sway, with an abnormally high sway path. The initial brain MRI was unremarkable. Due to the presumed cerebellar dysfunction we performed a second MRI 1 year later that disclosed deep cerebellar lesions compatible with LCH relapse within the CNS. The abnormal high SWJ rate and the impaired smooth pursuit performance correctly heralded later involvement of the cerebellum anticipating lesion appearance in the MRI.

Smooth ocular pursuit in Chiari type II malformation.

Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, both important structures for processing smooth ocular pursuit. CII is associated with myelomeningocele and hydrocephalus. We investigated the effects of CII on smooth pursuit (SP) eye movements, and determined the effects of spinal lesion level, number of shunt revisions, nystagmus, and brain dysmorphology on SP. SP was recorded using an infrared eye tracker in 21 participants with CII (11 males, 10 females; age range 8-19y, mean 14y 3mo [SD 3y 2mo]). Thirty-eight healthy children (21 males, 17 females) constituted the comparison group. Participants followed a visual target moving sinusoidally at +/- 10 degrees amplitude, horizontally and vertically at 0.25 or 0.5Hz. SP gains, the ratio of eye to target velocities, were abnormal in the CII group with nystagmus (n= 8). The number of shunt revisions (range 0-10), brain dysmorphology, or spinal lesion level (n= 15 for lower and n= 6 for upper spinal lesion level) did not correlate with SP gains. SP is impaired in children with CII and nystagmus. Abnormal pursuit might be related to the CII dysgenesis or to effects of hydrocephalus. The lack of effect of shunt revisions and abnormal tracking in participants with nystagmus provide evidence that it is related primarily to the cerebellar and brainstem malformation.

Neurological features of congenital fibrosis of the extraocular muscles type 2 with mutations in PHOX2A.

Congenital fibrosis of the extraocular muscles type 2 (CFEOM2) is a complex strabismus syndrome that results from mutations in the homeodomain transcription factor PHOX2A. To define the clinical and neuroimaging features of patients with this autosomal recessive syndrome, we studied 15 patients with genetically defined CFEOM2. All patients underwent full neurological, neuro-ophthalmological and orthoptic assessments. Twelve patients had pupillary pharmacological testing and nine had 3.0 tesla MRI of the brain, brainstem and orbits. Patients were born with severe bilateral ptosis and exotropia with almost complete bilateral absence of adduction, elevation, depression and intorsion. Variable abduction was present prior to strabismus surgery in 14 patients, and central ocular motility reflexes (smooth pursuit, saccades, vestibulo-ocular reflex and optokinetic reflex) were intact except for convergence. Pupillary light and near reflexes were not present, but irises were anatomically normal and responded to pupillary pharmacology. Neuroimaging of brain and brainstem was remarkable for the anatomical absence of cranial nerve (CN) 3 and probably CN 4 bilaterally. Therefore, the CFEOM2 phenotype and neuroimaging are both consistent with the congenital absence of CNs 3 and 4. Additional features included presence of most central ocular motility reflexes, a central lack of pupillary responsiveness of uncertain aetiology and modest phenotypic variability that does not correlate with specific PHOX2A mutations. Clinical presentation, neuroimaging and Phox2a-/- animal models all support the concept that CFEOM2 is a primary neurogenic abnormality with secondary myopathic changes.

Influence of cognitive expectation on the initiation of anticipatory and visual pursuit eye movements in the rhesus monkey.

A classic paradigm to study anticipatory pursuit consists in training monkeys to look at a target that appears in the center of a visual display, disappears during a short "gap" period, then reappears and immediately starts to move. To determine the role of prior directional information on anticipatory pursuit eye movements, we trained rhesus monkeys to associate the color of a centrally presented visual cue with the direction of an upcoming target motion. In a first experiment, a gap period occurred randomly in 50% of the trials. Consequently, two possible choices of timing of target motion onset were given to subjects to guide their anticipatory responses. In a second experiment, a gap period occurred during each trial and only a single choice of timing of target motion onset was given to subjects. We found that monkeys used the learned association between the color of the cue and the direction of future target motion to voluntarily initiate anticipatory pursuit movements in the appropriate direction. Anticipatory movements could be classified in two distinct populations: early and late movements. Early movements were most frequent when prior directional information was provided and when two choices of timing of target motion onset were given. The latency of visual pursuit was shortened and its velocity was larger when prior directional information was provided. We conclude that cognitive expectation of future target motion plays a dominant role in determining characteristics of anticipatory pursuit in the monkey.

Smooth pursuit-like eye movements during mental extrapolation of motion: the facilitatory effect of drowsiness.

We studied eye movements during mental extrapolation of motion. Subjects tracked with the eyes a target oscillating sinusoidally by +/- 5 degrees on the horizontal plane at frequencies between 0.15 and 0.5 Hz. After 4 cycles the target disappeared and subjects had to mentally extrapolate its motion in imagery for 5 further cycles. Subjects were invited to relax. We recorded eye movements with infrared oculography and the lid aperture with a webcam. Typically, in the imagery phase, sequences of saccades "reproduced" the macroscopic characteristics of the to-be-imagined motion. However, slow eye movements substituting the sequence of saccades emerged repeatedly in the course of the experiment, to the extent that sometimes it was almost impossible to distinguish the pattern of eye movements during tracking from that during imagery. These smooth pursuit-like eye movements lasted up to 17 s, although they were more commonly intermingled with saccades. It turned out that this phenomenon occurred mostly, although not exclusively, when the lids were partially lowered suggesting an association with drowsiness. The average gain of smooth pursuit-like eye movements in imagery passed from 0.09 when the lids were open, to 0.27 when they were partially lowered. A control experiment excluded that the lowering of the lids per se had played any important role. This finding has implications for both the physiology of the oculomotor system and for the debate on the relation between imagery and perception.

FMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia.

OBJECTIVE: Nicotine temporarily normalizes smooth pursuit eye movement deficits in schizophrenia. This study used functional magnetic resonance imaging (fMRI) to examine changes in brain hemodynamic response associated with nicotine administration during a smooth pursuit eye movement task in subjects with schizophrenia. METHOD: Nine subjects with schizophrenia performed the eye movement task while undergoing fMRI. Subjects then were given nicotine or placebo and repeated the task while being scanned. Subjects repeated the procedure the following week, receiving the counterbalanced condition. RESULTS: Compared with placebo, nicotine was associated with greater activity in the anterior and posterior cingulate gyri, precuneus, and area MT/MST and less activity in the hippocampus and parietal eye fields. CONCLUSIONS: Changes in area MT/MST and the cingulate gyrus are consistent with an improvement in perception and attention to moving stimuli. The most important observed difference between nicotine and placebo--less activation of the hippocampus after nicotine than after placebo administration--is consistent with nicotinic receptor mediation of inhibitory neuronal dysfunction in schizophrenia.