An fMRI study on smooth pursuit and fixation suppression of the optokinetic reflex using similar visual stimulation

This study compares brain activation patterns evoked by smooth pursuit and by fixation suppression of the optokinetic reflex (OKR) using similar retinal stimulation. Functional magnetic resonance imaging (fMRI) was performed during smooth pursuit stimulation in which a moving target was presented on a stationary pattern of stripes, and during fixation suppression of OKR in which a stationary target was presented on a moving pattern of stripes. All subjects could effectively ignore the background pattern and were able to keep the target continuously on the fovea with few saccades, in both experiments. Smooth pursuit evoked activation in the frontal eye fields (FEF), the supplementary eye fields (SEF), the parietal eye fields (PEF), the motion-sensitive area (MT/V5), and in lobules and vermis VI of the cerebellum (oculomotor areas). Fixation suppression of OKR induced activation in the FEF, PEF, and MT/V5. The direct comparison analysis revealed more activation in the right lobule VI of the cerebellum and in the right lingual and calcarine gyri during smooth pursuit than during fixation suppression of OKR. Using similar retinal stimulation, our results show that smooth pursuit and fixation suppression of the OKR appear to activate largely overlapping pathways. The increased activity in the oculomotor areas of the cerebellum during smooth pursuit is probably due to the presence of an active eye movement component.     

Development of prosaccade and antisaccade task performance in participants aged 6 to 26 years

There are few studies on the development of oculomotor functions during childhood. B. Fischer, M. Biscaldi, and S. Gezeck (1997) reported improvement of antisaccade task performance between ages 6 and 16 years. The present study is a replication and extension of those results. In three age groups (6-7, 10-11, 18-26 years), saccades during pro- and antisaccade tasks with 200-ms gap and overlap and during a fixation task were measured. Adults exhibited faster saccades and less prosaccades during the antisaccade tasks than 10-11-year-old children; these two groups had faster saccades during all tasks and less prosaccades during the anti- and the fixation task than 6-7-year-old subjects. Both children groups made more express saccades than adults. Results suggest different degrees of age-related improvement for different saccadic parameters, the effects being greatest for prosaccade inhibition during the antisaccade task and in line with the assumed protracted development of prefrontal functions.     

Dopamine D1 receptors and age differences in brain activation during working memory

In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [¹¹C] SCH23390 to determine dopamine D₁ receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load > lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D₁ BP in caudate and DLPFC. Statistical control of caudate and DLPFC D₁ binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.     

Executive functions and neurocognitive aging: dissociable patterns of brain activity

Studies of neurocognitive aging report altered patterns of brain activity in older versus younger adults performing executive function tasks. We review the extant literature, using activation likelihood estimation meta-analytic methods, to compare age-related differences in the pattern of brain activity across studies examining 2 categories of tasks associated with executive control processing: working memory and inhibition. In a direct contrast of young and older adult activations, older adults engaged bilateral regions of dorsolateral prefrontal cortex as well as supplementary motor cortex and left inferior parietal lobule during working memory. In contrast, age-related changes during inhibitory control were observed in right inferior frontal gyrus and presupplementary motor area. Additionally, when we examined task-related differences within each age group we observed the predicted pattern of differentiated neural response in the younger subjects: lateral prefrontal cortex activity associated with working memory versus right anterior insula/frontal opercular activity associated with inhibition. This separation was largely maintained in older subjects. These data provide the first quantitative meta-analytic evidence that age-related patterns of functional brain change during executive functioning depend on the specific control process being challenged.     

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.     

Human Variability of fMRI Brain Activation in Response to Oculomotor Stimuli

Assessing interindividual variability of brain activation is of practical importance to the use of functional magnetic resonance imaging (fMRI) in the clinical context. The main objective of this study is to analyze the variability of the oculomotor system through horizontal optokinetic, pursuit and saccadic eye movement stimulations by means of fMRI. We found significant activation of many cortical and subcortical structures. The frequency of activation demonstrates a high variability between subjects. However, the most frequent activation regions were located in frontal areas and in regions comprising the middle temporal and medial superior temporal areas. Our study allowed the characterization of the most frequently involved foci in optokinetic stimulation, pursuit and saccadic eye movement tasks. The combination of these tasks constitutes a suitable tool for mapping major areas involved in the oculomotor system. This work was done at the University of Sao Paulo, Campus Ribeirao Preto, Brazil.     

Differences in cortical activation during smooth pursuit and saccadic eye movements following cerebellar lesions

Current evidence supports the proposal that the cerebellum mediates the activity of other brain areas involved in the control of eye movements. Most of the evidence so far has concentrated on the vermis and flocculi as the cerebellar agents of oculomotor control. But there is also evidence for an involvement of the cerebellar hemispheres in eye movement control. Straube et al. (Ann Neurol 42:891–898, 1997) showed that lateral hemispheric lesions affect initiation of smooth pursuit (SPEM) and saccadic eye movements. Ron and Robinson (J Neurophysiol 36:1004–1022, 1973) evoked smooth pursuit and saccadic eye movements by electrical stimulation of crus I and II, as well as in the dentate nuclei of the monkey. Functional MRI studies also provide evidence that the cerebellar hemispheres play a significant role in SPEM and saccadic eye movements. To clarify the role of the cerebral hemispheres in eye movement control we compared the eye movement related blood oxygen level dependent (BOLD) responses of 12 patients with cerebellar lesions due to stroke with those of an aged-matched healthy control group. Six patients showed oculomotor abnormalities such as dysmetric saccades or saccadic SPEM during the experiment. The paradigm consisted of alternating blocks of fixation, visually guided saccades and visually guided SPEM. A nonparametric random-effects group analysis showed a degraded pattern of activation in the patient group during the performance of SPEM and saccadic eye movements in posterior parietal areas putatively containing the parietal eye fields.     

Impaired eye tracking performance in patients with presenile onset dementia.

Smooth pursuit eye movements, saccades and eye blinks were electrooculographically recorded from 26 healthy subjects of different age and 35 patients with presumptive presenile onset dementia (mean age 54), who had to track a light spot which oscillated with different speeds. Older subjects (mean age 51) performed the eye tracking with less accuracy and more saccades than younger ones (mean age 22). 16 patients with stage CDR 1 according to Washington University Clinical Dementia Rating performed smooth pursuit eye movements significantly worse with increased saccade numbers than the healthy older subjects and lost attention significantly more often which was measured by omitted trackings to presented target oscillations. Their number of eye blinks was partly increased. The test is found suitable for early diagnosis of dementia onset, supporting clinical findings and presumptive diagnosis by objective parameters.     

Neural basis of visually guided head movements studied with fMRI

We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus. These areas have been previously observed in functional imaging studies of human eye movements, suggesting that a common set of brain areas subserves both oculomotor and head movement control in humans, consistent with data from single-unit recording and microstimulation studies in nonhuman primates that have described overlapping eye- and head-movement representations in oculomotor control areas. A second set of areas was active during head and gaze movements but not during eye movements. This set of areas included the posterior part of the planum temporale and the cortex at the temporoparietal junction, known as the parieto-insular vestibular cortex (PIVC). Activity in PIVC has been observed during imaging studies of invasive vestibular stimulation, and we confirm its role in processing the vestibular cues accompanying natural head movements. Our findings demonstrate that fMRI can be used to study the neural basis of head movements and show that areas that control eye movements also control head movements. In addition, we provide the first evidence for brain activity associated with vestibular input produced by natural head movements as opposed to invasive caloric or galvanic vestibular stimulation.     

Age-related decline of peripheral visual processing: the role of eye movements

Earlier work suggests that the area of space from which useful visual information can be extracted (useful field of view, UFoV) shrinks in old age. We investigated whether this shrinkage, documented previously with a visual search task, extends to a bimanual tracking task. Young and elderly subjects executed two concurrent tracking tasks with their right and left arms. The separation between tracking displays varied from 3 to 35 cm. Subjects were asked to fixate straight ahead (condition FIX) or were free to move their eyes (condition FREE). Eye position was registered. In FREE, young subjects tracked equally well at all display separations. Elderly subjects produced higher tracking errors, and the difference between age groups increased with display separation. Eye movements were comparable across age groups. In FIX, elderly and young subjects tracked less well at large display separations. Seniors again produced higher tracking errors in FIX, but the difference between age groups did not increase reliably with display separation. However, older subjects produced a substantial number of illicit saccades, and when the effect of those saccades was factored out, the difference between young and older subjects’ tracking did increase significantly with display separation in FIX. We conclude that the age-related shrinkage of UFoV, previously documented with a visual search task, is observable with a manual tracking task as well. Older subjects seem to partly compensate their deficit by illicit saccades. Since the deficit is similar in both conditions, it may be located downstream from the convergence of retinal and oculomotor signals.     

Age-related trends in saccade characteristics among the elderly

Eye movement recordings are useful for assessing neurological disorders, the prevalence of which increases with age. However, there is little rigorous quantitative data on describing oculomotor changes that occur during healthy aging. Here, we measured the ability of 81 normal elderly subjects (60-85 years) to perform two saccadic eye movement tasks: a pro-saccade task, requiring an automatic response to look towards a stimulus and an anti-saccade task, requiring inhibition of the automatic response to instead initiate a voluntary saccade away from the stimulus. Saccadic ability decreased with age: the oldest subjects were slower to initiate saccades and they made more direction errors (i.e., erroneous pro-saccades) in the anti-saccade task. Intra-subject variability in reaction time also correlated positively with age in both saccade tasks. Voluntary saccade control, as assessed by the anti-saccade task, was far more affected by aging than automatic control, as assessed by the pro-saccade task, suggesting that the mechanisms driving voluntary and automatic saccade performance deteriorate at different rates in the aging brain, and therefore likely involves different neural substrates. Our data provide insight into deficits due to normal brain changes in aging as well as a baseline to evaluate deficits caused by neurological disorders common in this age range.     

Inhibitory control of attention declines more than working memory during normal aging

Changes in frontostriatal systems are believed to reduce the efficiency of executive cognitive functions during normal aging, especially the inhibitory control of attentional and behavioral responses. To characterize changes during normal aging in sensorimotor, working memory and inhibitory attentional systems, we tested 20 healthy elderly subjects (age 65-80) and 28 young adults (age 18-34) using oculomotor paradigms. Visually guided saccades of elderly subjects showed decreased peak velocity and increased reaction time, but not reduced accuracy, indicating selective age-related declines in sensorimotor systems. In an oculomotor working memory task, memory for spatial location information in elderly subjects was as accurate as in young adults. In contrast, elderly subjects demonstrated a significantly reduced ability to voluntarily inhibit eye movements toward flashed targets on an antisaccade task. These findings indicate changes in frontostriatal systems during normal aging that adversely affect volitional inhibitory processes but spare encoding and retrieval components of spatial working memory.     

Neural activation associated with corrective saccades during tasks with fixation,pursuit and saccades

Corrective saccades are small eye movements that redirect gaze whenever the actual eye position differs from the desired eye position. In contrast to various forms of saccades including pro-saccades, recentering-saccades or memory guided saccades, corrective saccades have been widely neglected so far. The fMRI correlates of corrective saccades were studied that spontaneously occurred during fixation, pursuit or saccadic tasks. Eyetracking was performed during the fMRI data acquisition with a fiber-optic device. Using a combined block and event-related design, we isolated the cortical activations associated with visually guided fixation, pursuit or saccadic tasks and compared these to the activation associated with the occurrence of corrective saccades. Neuronal activations in anterior inferior cingulate, bilateral middle and inferior frontal gyri, bilateral insula and cerebellum are most likely specifically associated with corrective saccades. Additionally, overlapping activations with the established pro-saccade and, to a lesser extent, pursuit network were present. The presented results imply that corrective saccades represent a potential systematic confound in eye-movement studies, in particular because the frequency of spontaneously occurring corrective saccades significantly differed between fixation, pursuit and pro-saccades.     

Inhibition of return in children with attention deficit hyperactivity disorder

Earlier studies have suggested an impairment in the attention and eye movement control of children with ADHD. An important phenomenon in the control of attentional shifts and eye movements is the inhibition of return (IOR), which states that our brain works in a way that prevents our attention from returning to a spatial location that has been attended to, either overtly or covertly. This current study addresses whether the IOR in oculomotor planning is compromised in children with ADHD. Eleven ADHD and 12 age- and gender-matched control subjects participated in a behavioral task, in which they made saccades to a peripheral target after a valid, invalid or neutral cue. The latency difference between cued and uncued saccades over a range of cue-target onset asynchrony as well as the positive component of this latency profile (i.e., IOR) was compared between groups. The results show that ADHD children demonstrate a biphasic latency profile that is grossly similar to that observed in control subjects, although the magnitude of IOR appears to be slightly smaller in ADHD subjects. These preliminary results suggest that the inhibitory attention mechanism subserving IOR is at least not fully compromised in ADHD children. Electronic Publication     

Chameleons have independent eye movements but synchronise both eyes during saccadic prey tracking

The movements of both eyes and the head were recorded with search coils in unrestrained, freely moving chameleons. As a main result I found that the generation of saccades in the left and the right eye was either independent from each other or was highly correlated according to the behavioural situation. When no prey item was fixated, disconjugate saccades were observed which was in accordance with earlier observations in chameleons. During prey tracking the chameleons switched to a different oculomotor behaviour and pursued the moving prey with synchronous saccades. At higher target velocities, the tracking movement of the head was also saccadic and was synchronised with the two eyes. Binocular coupling affected only the timing of the saccades but not the metrics: the amplitudes of the synchronous saccades were usually different in the two eyes. These observations suggest the existence of two independent premotor neuronal circuits for left and right eye saccadic motor control in the chameleon. Binocular coupling in prey-tracking chameleons is probably achieved by neuronal coupling of these premotor circuits during eye–head coordination. The ability to switch between synchronous and uncoupled saccadic eye movements has not been described for any other vertebrate. This unique ability of the chameleon may help to understand the organisation of the oculomotor system of other vertebrates since evidence for separate left eye and right eye saccade generation and position control has recently also been reported in primates. Electronic Publication     

Adult age differences in the functional neuroanatomy of visual attention: a combined fMRI and DTI study

We combined measures from event-related functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and cognitive performance (visual search response time) to test the hypotheses that differences between younger and older adults in top-down (goal-directed) attention would be related to cortical activation, and that white matter integrity as measured by DTI (fractional anisotropy, FA) would be a mediator of this age-related effect. Activation in frontal and parietal cortical regions was overall greater for older adults than for younger adults. The relation between activation and search performance supported the hypothesis of age differences in top-down attention. When the task involved top-down control (increased target predictability), performance was associated with frontoparietal activation for older adults, but with occipital (fusiform) activation for younger adults. White matter integrity (FA) exhibited an age-related decline that was more pronounced for anterior brain regions than for posterior regions, but white matter integrity did not specifically mediate the age-related increase in activation of the frontoparietal attentional network.     

Effect of retinal and/or extra-retinal information on age in memory-guided saccades

The aim of the study was to determine whether the addition of retinal or extra-retinal information could be used to improve memory-guided saccadic performance in healthy participants. Furthermore, we included two age groups in our study; healthy young adult subjects (mean age 20 years) and healthy middle-aged adult subjects (mean age 52 years). All subjects performed a novel task that incorporated a Go/NoGo task with a memory-guided saccade paradigm to investigate whether extra-retinal information (making a saccade towards the visible target) or retinal (a visible frame-of-reference) has any affect on the accuracy or variability of the response. We found all subjects made slight hypometric responses to the memory-guided targets. Both younger and middle-aged subjects revealed an increase in accuracy in the Go task compared with the NoGo task and the framed condition compared to the frameless condition, respectively. The frame also revealed a significant decrease in variability in the memory-guided saccades. A positive correlation in errors between the 1st and 2nd saccade in the Go task was revealed for all subjects; however, the older subjects revealed a greater correlation than younger subjects. The results presented indicate that younger and middle-aged perform highly similar patterns of errors during eye movements to remembered locations. However, middle-aged subjects show a greater tendency to use extra-retinal and retinal feedback to guide the response.     

Effect of aging on the human initial interaural linear vestibulo-ocular reflex

To determine age-related changes, the initial linear vestibulo-ocular reflex (LVOR) of eight older subjects of mean age 65+/-7 years (mean +/- SD, range 56-75 years) was compared with that of nine younger subjects of mean age 24+/-5 years (range 18-31 years) in response to random transients of whole-body heave (interaural) translation at peak acceleration of 0.5 g delivered by a pneumatic actuator. Binocular eye rotations were measured with magnetic search coils, while linear head position and acceleration were measured with a potentiometer and piezoelectric accelerometer. Subjects viewed targets 200 cm, 50 cm, or 15 cm distant immediately before the unpredictable onset of randomly directed translation in darkness (LVOR) and in light (LVVOR). All subjects maintained ideal vergence of 1.5-2 degrees for the 200-cm target, 6-8 degrees for the 50-cm target, and 21-26 degrees for the 15-cm target, with actual vergences depending on individual interpupillary distances. Search coil recording of angular position of the upper teeth showed head rotation to be negligible (less than 0.5 degrees ) for the first 250 ms after onset of head translation, excluding a role for the angular VOR in the responses studied. The LVOR response to heave translation was an oppositely directed eye rotation occurring after a mean latency of 62+/-3 ms for older and 42+/-3 ms (mean +/- SD) for younger subjects ( P<0.0001). The peak of the latency distribution was 60-100 ms for older and 20-60 ms for younger subjects. During the early interval, 70-80 ms from head motion onset prior to a pursuit contribution or saccades, all subjects had significantly enhanced LVOR with decreasing target distance. In this interval, the LVOR position amplitude of younger subjects was 0.17+/-0.01 degrees, 0.40+/-0.01 degrees, 0.57+/-0.01 degrees (mean +/- SE), respectively, in descending order of target distance. Early sensitivities were significantly reduced for older subjects to 0.07+/-0.01 degrees, 0.23+/-0.01 degrees, 0.40+/-0.01 degrees ( P<0.0001). There was no significant effect of target visibility in either group during the first 110 ms ( P>0.05). Visual-otolith interaction was mainly reflected not by the vestibular slow phase, but by vestibular catch-up saccades (VCUS) in the compensatory direction. The effect of aging on the initial human LVOR is thus to: prolong latency, reduce early sensitivity, and reduce occurrence of vestibular catch-up saccades.     

Comparison of memory- and visually guided saccades using event-related fMRI

Previous functional imaging studies have shown an increased hemodynamic signal in several cortical areas when subjects perform memory-guided saccades than that when they perform visually guided saccades using blocked trial designs. It is unknown, however, whether this difference results from sensory processes associated with stimulus presentation, from processes occurring during the delay period before saccade generation, or from an increased motor signal for memory-guided saccades. We conducted fMRI using an event-related paradigm that separated stimulus-related, delay-related, and saccade-related activity. Subjects initially fixated a central cross, whose color indicated whether the trial was a memory- or a visually guided trial. A peripheral stimulus was then flashed at one of 4 possible locations. On memory-guided trials, subjects had to remember this location for the subsequent saccade, whereas the stimulus was a distractor on visually guided trials. Fixation cross disappearance after a delay period was the signal either to generate a memory-guided saccade or to look at a visual stimulus that was flashed on visually guided trials. We found slightly greater stimulus-related activation for visually guided trials in 3 right prefrontal regions and right rostral intraparietal sulcus (IPS). Memory-guided trials evoked greater delay-related activity in right posterior inferior frontal gyrus, right medial frontal eye field, bilateral supplementary eye field, right rostral IPS, and right ventral IPS but not in middle frontal gyrus. Right precentral gyrus and right rostral IPS exhibited greater saccade-related activation on memory-guided trials. We conclude that activation differences revealed by previous blocked experiments have different sources in different areas and that cortical saccade regions exhibit delay-related activation differences.     

White matter hyperintensities alter functional organization of the motor system

Severe white matter hyperintensities (WMH) represent cerebral small vessel disease and predict functional decline in the elderly. We used fMRI to test if severe WMH impact on functional brain network organization even before clinical dysfunction. Thirty healthy right-handed/footed subjects (mean age, 67.8 ± 7.5 years) underwent clinical testing, structural MRI and fMRI at 3.0T involving repetitive right ankle and finger movements. Data were compared between individuals with absent or punctuate (n = 17) and early confluent or confluent (n = 13) WMH. Both groups did not differ in mobility or cognition data. On fMRI, subjects with severe WMH demonstrated excess activation in the pre-supplementary motor area (SMA), frontal, and occipital regions. Activation differences were noted with ankle movements only. Pre-SMA activation correlated with frontal WMH load for ankle but not finger movements. With simple ankle movements and no behavioral deficits, elderly subjects with severe WMH demonstrated pre-SMA activation, usually noted with complex tasks, as a function of frontal WMH load. This suggests compensatory activation related to disturbance of frontosubcortical circuits.