H. Kimmig

Event-related fMRI responses in the human frontal eye fields in a randomized pro- and antisaccade task

We examined whether the frontal eye fields (FEF) are involved in the suppression of reflexive saccades. Simultaneous recording of horizontal eye movements and functional magnetic resonance imaging enabled us to perform a randomized pro- and antisaccade task and to sort blood oxygenation level dependent (BOLD) time series on the basis of task performance. Saccadic reaction time distributions were comparable across tasks indicating a similar effort in preprocessing of the saccades. Furthermore, we found similar BOLD activation in FEF during both correctly performed pro- and antisaccades. Frontal eye field activation started prior to target presentation and saccade generation. While we observed only few erroneous antisaccades, these were associated with a decrease in BOLD activity prior to target presentation, and increased BOLD activity after target presentation relative to correctly performed antisaccades. These findings are consistent with a role of the FEF in the suppression of reflexive saccades. The increase in activity after target presentation for antisaccade errors can only be indirectly linked to such a role but may also reflect activity related to the generation of a correction saccade. Frontal eye field BOLD activity may further represent general arousal, preparatory set, shortterm memory, or salience-map related activity.

MR-eyetracker: a new method for eye movement recording in functional magnetic resonance imaging.

Abstract We present a method for recording saccadic and pursuit eye movements in the magnetic resonance tomograph designed for visual functional magnetic resonance imaging (fMRI) experiments. To reliably classify brain areas as pursuit or saccade related it is important to carefully measure the actual eye movements. For this purpose, infrared light, created outside the scanner by light-emitting diodes (LEDs), is guided via optic fibers into the head coil and onto the eye of the subject. Two additional fiber optical cables pick up the light reflected by the iris. The illuminating and detecting cables are mounted in a plastic eyepiece that is manually lowered to the level of the eye. By means of differential amplification, we obtain a signal that covaries with the horizontal position of the eye. Calibration of eye position within the scanner yields an estimate of eye position with a resolution of 0.2° at a sampling rate of 1000 Hz. Experiments are presented that employ echoplanar imaging with 12 image planes through visual, parietal and frontal cortex while subjects performed saccadic and pursuit eye movements. The distribution of BOLD (blood oxygen level dependent) responses is shown to depend on the type of eye movement performed. Our method yields high temporal and spatial resolution of the horizontal component of eye movements during fMRI scanning. Since the signal is purely optical, there is no interaction between the eye movement signals and the echoplanar images. This reasonably priced eye tracker can be used to control eye position and monitor eye movements during fMRI.

Changes in cortical activation during mirror reading before and after training: an fMRI study of procedural learning.

The neural correlates of procedural learning were studied using functional magnetic resonance imaging (fMRI) and the mirror reading paradigm. The aim of the study was to investigate a presumed learning-related change of activation in cortical areas that are involved in the performance of a nonmotor skill. Changes in cortical blood oxygenation contrast were recorded in 10 healthy subjects while they alternatively read visually presented single mirror script words and normal script words. Responses in naive subjects were compared to those acquired after training of mirror script reading. The acquisition volume included the motor and premotor cortex, the parietal lobe and the occipital lobe including its inferior aspects. Striate and extrastriate visual areas, associative parietal cortex and the premotor cortex were bilaterally active during normal and mirror script reading. Significantly stronger activation during mirror reading was seen in BA7 and 40 (parietal associative cortex) and in BA6 (corresponding to the frontal eye fields). Simultaneous eye movement recordings indicated that activation in BA6 was related to processing components other than saccade frequency. After training, BA6 and BA7 exhibited a decrease of activation during mirror reading that significantly exceeded nonspecific changes observed in the normal script control condition. The present findings confirm the hypothesis of practice-related decrease of activation in task-related cortical areas during nonmotor procedural learning.

What is pathological with gaze shift fragmentation in Parkinson's disease?

Abstract. Oculomotor dysfunction in Parkinsons disease (PD) is mainly characterized by a fragmentation of memory-guided gaze shifts (target is reached by several hypometric saccades). Since this phenomenon can also be observed in normal subjects, we scrutinized its pathophysiological significance in PD patients. We recorded horizontal eye movements in eleven mildly- or moderately-affected PD patients and eleven control subjects. A quantitative assessment of gaze shift fragmentation was made possible by increasing its incidence over a sequence of two visually- and two subsequent memory-guided gaze shifts. Basic saccade measures (latency, velocity, etc.) were similar in the two subject groups as well as in fragmented versus non-fragmented gaze shifts. Fragmentation probability is increased in the second memory-guided gaze shift, and this clearly more so in patients than in controls. The fragmentation shows a typical gain pattern (uniform increase of gain of saccadic amplitudes across correction saccades towards 1.0 with the last saccade of the gaze shift) independent of subject group, stimulus mode, and fragmentation degree. Gaze shift fragmentation represents a physiological phenomenon, which has thus far been overlooked. It reflects a robust correction mechanism, which assures that target is reached even if the pre-oculomotor drive through the basal ganglia to the superior colliculus becomes abnormally weak or under inadequately strong inhibition – as is postulated for PD. Thus, only the abnormally high incidence of fragmentation, and of the associated amplitude reduction of the primary saccades, rather than the phenomenon per se, can be used as a diagnostic criterion in early stages of PD.

Gaze pursuit, ‘attention pursuit’ and their effects on cortical activations

A moving object draws our attention to it and we can track the object with smooth pursuit eye movements (SPEM). Gaze and attention are usually directed to the same object during SPEM. In this study we investigated whether gaze and attention can be divided during pursuit. We explored the cortical control of ocular tracking and attentive tracking and the role of focused and divided attention. We presented a sinusoidally moving target for pursuit and simultaneously a stationary target for fixation. Gaze could be directed to the pursuit target and attention to the fixation target or vice versa, or gaze and attention were directed to the same (moving or stationary) target. We found that gaze (overt) and attentive (covert) pursuit similarly activated the cortical oculomotor network. Gaze pursuit showed higher activations than attentive pursuit. Activations, specific to the dissociation of attention from gaze and independent of eye movements, were found solely in the posterior parietal cortex. A cue indicating a forthcoming attention task activated large parts of the cortical SPEM network, as a kind of preparatory mechanism. We did not find any attention‐related regions outside the well‐known visuo‐oculomotor network. We conclude that attention control during gaze pursuit and gaze fixation occur within the cortical SPEM network, supporting the premotor theory of attention [Rizzolatti, G., Riggio, L., Dascola, I. & Umilta, C. (1987) Neuropsychologia, 25, 31–40].

Sleep is required for improving reaction times after training on a procedural visuo-motor task

Sleep has been found to enhance consolidation of many different forms of memory. However in most procedural tasks, a sleep-independent, fast learning component interacts with slow, sleep-dependent improvements. Here, we show that in humans a visuo-motor saccade learning task shows no improvements during training, but only during a delayed recall testing after a period of sleep. Subjects were trained in a prosaccade task (saccade to a visual target). Performance was tested in the prosaccade and the antisaccade task (saccade to opposite direction of the target) before training, after a night of sleep or sleep deprivation, after a night of recovery sleep, and finally in a follow-up test 4 weeks later. We found no immediate improvement in saccadic reaction time (SRT) during training, but a delayed reduction in SRT, indicating a slow-learning process. This reduction occurred only after a period of sleep, i.e. after the first night in the sleep group and after recovery sleep in the sleep deprivation group. This improvement was stable during the 4-week follow-up. Saccadic training can thus induce covert changes in the saccade generation pathway. During the following sleep period, these changes in turn bring about overt performance improvements, presuming a learning effect based on synaptic tagging.

Visual Search Disorders in Acute and Chronic Homonymous Hemianopia: Lesion Effects and Adaptive Strategies

Patients with homonymous hemianopia due to occipital brain lesions show disorders of visual search. In everyday life this leads to difficulties in reading and spatial orientation. It is a matter of debate whether these disorders are due to the brain lesion or rather reflect compensatory eye movement strategies developing over time. For the first time, eye movements of acute hemianopic patients (n= 9) were recorded during the first days following stroke while they performed an exploratory visual‐search task. Compared to age‐matched control subjects their search duration was prolonged due to increased fixations and refixations, that is, repeated scanning of previously searched locations. Saccadic amplitudes were smaller in patients. Right hemianopic patients were more impaired than left hemianopic patients. The number of fixations and refixations did not differ significantly between both hemifields in the patients. Follow‐up of one patient revealed changes of visual search over 18 months. By using more structured scanpaths with fewer saccades his search duration decreased. Furthermore, he developed a more efficient eye‐movement strategy by making larger but less frequent saccades toward his blind side. In summary, visual‐search behavior of acute hemianopic patients differs from healthy control subjects and from chronic hemianopic patients. We conclude that abnormal visual search in acute hemianopic patients is related to the brain lesion. We provide some evidence for adaptive eye‐movement strategies developed over time. These adaptive strategies make the visual search more efficient and may help to compensate for the persisting visual‐field loss.

Eye movements during REM sleep and imagination of visual scenes

It has been hypothesized that rapid eye movements (REMs) during sleep reflect the process of looking around in dreams. We questioned whether REMs differ from eye movements in wakefulness while imagining previously seen visual stimuli (dots, static images, videos). After looking at these stimuli individuals were asked to remember and imagine them. Subsequently, their REMs were recorded at the sleep laboratory. Kinematic parameters of REMs were similar to saccadic eye movements to remembered stimuli with closed eyes, irrespective of the stimulus type. In contrast, peak velocity of eye movements with open eyes was similar to REMs when semantic, but not nonsemantic, contents were imagined. Thus, REMs may be related to exploratory saccadic behaviour in the awake to remember visual stimuli.

Optic Flow Stimuli in and Near the Visual Field Centre: A Group fMRI Study of Motion Sensitive Regions

Motion stimuli in one visual hemifield activate human primary visual areas of the contralateral side, but suppress activity of the corresponding ipsilateral regions. While hemifield motion is rare in everyday life, motion in both hemifields occurs regularly whenever we move. Consequently, during motion primary visual regions should simultaneously receive excitatory and inhibitory inputs. A comparison of primary and higher visual cortex activations induced by bilateral and unilateral motion stimuli is missing up to now. Many motion studies focused on the MT+ complex in the parieto-occipito-temporal cortex. In single human subjects MT+ has been subdivided in area MT, which was activated by motion stimuli in the contralateral visual field, and area MST, which responded to motion in both the contra- and ipsilateral field. In this study we investigated the cortical activation when excitatory and inhibitory inputs interfere with each other in primary visual regions and we present for the first time group results of the MT+ subregions, allowing for comparisons with the group results of other motion processing studies. Using functional magnetic resonance imaging (fMRI), we investigated whole brain activations in a large group of healthy humans by applying optic flow stimuli in and near the visual field centre and performed a second level analysis. Primary visual areas were activated exclusively by motion in the contralateral field but to our surprise not by central flow fields. Inhibitory inputs to primary visual regions appear to cancel simultaneously occurring excitatory inputs during central flow field stimulation. Within MT+ we identified two subregions. Putative area MST (pMST) was activated by ipsi- and contralateral stimulation and located in the anterior part of MT+. The second subregion was located in the more posterior part of MT+ (putative area MT, pMT).

Long-term eye movement recordings with a scleral search coil-eyelid protection device allows new applications

The search coil technique is regarded as the gold standard in eye movement recordings. The manufacturers of scleral search coils (SSC) do not recommend using them longer than 30 min. The temporal limitations result from potential cornea damage and from irritations of the lid margins and palpebral conjunctiva which subjects perceive as unpleasant. Here we introduce a new coil-eyelid protection device (CEPD) which allows recording intervals up to 2 h with considerably reduced discomfort. Ophthalmic examinations and saccade recordings were used for comparison with the conventional SSC recording technique. In three experiments subjects were examined using SSCs with a commercially available cornea bandage lens on top of the search coil up to 120 min recording time. Ophthalmic testing revealed no apparent harmful effects on eyes or lid surface. Saccade parameters (main sequence) remained unchanged comparing SSC and CEPD recordings. Subjects rated less discomfort by using the CEPD. For the first time we show that SSC recordings can be extended over about 120 min without hazard to the eye, when using an eyelid protection lens. This advanced method allows new applications like eye movement recordings during sleep (rapid eye movements) or perceptional or motor learning tasks, e.g. saccade adaptation paradigms.