Smooth-pursuit eye movement representation in the primate frontal eye field.

Physiological and behavioral data reported here show an involvement of the primate frontal eye field (FEF) cortex in smooth-pursuit eye movements, in addition to its well-established role in saccadic eye movements. Microstimulation just ventral to the small saccade representation of the FEF elicits eye movements that, in contrast to elicited saccades, have low velocities, continue smoothly without interruption during prolonged stimulation, and are usually directed ipsilaterally to the stimulated hemisphere. Neurons in this region respond in association with smooth-pursuit eye movements and visual motion. Tracking deficits following experimental lesions of the FEF depend critically upon the status of this ventral region: superficial lesions sparing it leave smooth-pursuit eye movements intact, whereas lesions removing it produce substantial deficits in the anticipatory initiation, motion-induced acceleration, asymptotic velocity, and predictive continuation of ipsilateral smooth pursuit.     

The planning and guiding of reading saccades: a repetitive transcranial magnetic stimulation study.

A previous positron emission tomography study that investigated the cortical areas involved in directing eye movements during text reading showed two areas of extra-occipital asymmetry: left > right posterior parietal cortex (PPC), and right > left frontal eye-field (FEF). We used the temporal resolution of repetitive TMS (rTMS) to isolate the contributions of the left and right PPC and FEF to the planning and execution of rightward reading saccades. We present eye-movement data collected during text reading, which involves the initiation and maintenance of a series of saccades (scanpath). rTMS over the left but not right PPC slowed reading speeds for the whole array of words, indicating that this area is involved throughout the scanpath. rTMS over the right but not the left FEF slowed the time to make the first saccade, but only when triggered before the stimuli appeared, demonstrating that the role of this region is in the preparation of the scanpath. Our results are compatible with the hypotheses that the left PPC maintains reading saccades along a line of text while the right FEF is involved in the preparation of the motor plan for the scanpath at the start of each new line of text.     

Functional neuroanatomy of anticipatory behavior: dissociation between sensory-driven and memory-driven systems

The ability to anticipate predictable stimuli allows faster responses. The predictive saccade (PRED) task has been shown to quickly induce such anticipatory behavior in humans. In a PRED task subjects track a visual target jumping back and forth between fixed positions at a fixed time interval. During this task, saccade latencies drop from approximately 200 ms to <80 ms as subjects anticipate target appearance. This change in saccade latency indicates that subjects' behavior shifts from being sensory driven to being memory driven. We conducted functional magnetic resonance imaging studies with 10 healthy adults performing the PRED task using a standard block design. We compared the PRED task with a visually guided saccade (VGS) task using unpredictable targets matched for number, direction and amplitude of required saccades. Our results show greater activation during the PRED task in the prefrontal, pre-supplementary motor and anterior cingulate cortices, hippocampus, mediodorsal thalamus, striatum and cerebellum. The VGS task elicited greater activation in the cortical eye fields and occipital cortex. These results demonstrate the important dissociation between sensory and predictive neural control of similar saccadic eye movements. Anticipatory behavior induced by the PRED task required less sensory-related processing activity and was subserved by a distributed cortico-subcortical memory system including prefronto-striatal circuitry.     

Enhanced motion sensitivity follows saccadic suppression in the superior temporal sulcus of the macaque cortex

The responses of neurons in the middle temporal and medial superior temporal areas of macaque cortex are suppressed during saccades compared with saccade-like stimulus movements. We utilized the short-latency ocular following paradigm to show that this saccadic suppression is followed by postsaccadic enhancement of motion responses. The level of enhancement decays with a time constant of 100 ms from saccade end. The speed of ocular following is also enhanced after saccades and decays over a similar time course, suggesting a link between the neural and behavioral effects. There is some evidence that maximum postsaccadic enhancement occurs when cells are stimulated at their optimum speeds. Latencies of motion responses are saccade dependent: 37 ms for saccade-generated motion, 45 ms for motion in the half-second after saccades, and 70 ms with no prior saccades. The finding that saccades alter response latencies may partially explain perceptual time compression during saccades and time dilation after saccades.     

Distribution of activity across the monkey cerebral cortical surface, thalamus and midbrain during rapid, visually guided saccades

To examine the distribution of visual and oculomotor activity across the macaque brain, we performed functional magnetic resonance imaging (fMRI) on awake, behaving monkeys trained to perform visually guided saccades. Two subjects alternated between periods of making saccades and central fixations while blood oxygen level dependent (BOLD) images were collected [3 T, (1.5 mm)3 spatial resolution]. BOLD activations from each of four cerebral hemispheres were projected onto the subjects' cortical surfaces and aligned to a surface-based atlas for comparison across hemispheres and subjects. This surface-based analysis revealed patterns of visuo-oculomotor activity across much of the cerebral cortex, including activations in the posterior parietal cortex, superior temporal cortex and frontal lobe. For each cortical domain, we show the anatomical position and extent of visuo-oculomotor activity, including evidence that the dorsolateral frontal activation, which includes the frontal eye field (on the anterior bank of the arcuate sulcus), extends anteriorly into posterior principal sulcus (area 46) and posteriorly into part of dorsal premotor cortex (area 6). Our results also suggest that subcortical BOLD activity in the pulvinar thalamus may be lateralized during voluntary eye movements. These findings provide new neuroanatomical information as to the complex neural substrates that underlie even simple goal-directed behaviors.     

Changes in ventilation and its components in normal subjects during sleep.

Non-invasive measurements were made of ventilation, its derivatives, the contributions of abdomen and rib cage and arterial oxygen saturation in six healthy normal men whilst awake and during sleep. Minute ventilation fell significantly during slow wave (SW) sleep and rapid eye movement (REM) sleep (awake = 6.3 1 min-1, SW sleep = 5.7 1 min-1, REM sleep = 5.4 1 min-1; p less than 0.04). Mean inspiratory flow also fell significantly but timing was unchanged. The abdominal (diaphragmatic) contribution to ventilation fell very significantly during SW sleep but returned to awake levels during REM sleep (awake 54%, SW sleep 38%, REM sleep 56%; p less than 0.007). There were also significant falls in arterial oxygen saturation during SW and REM sleep (awake 97.3%, SW sleep 96.5%, REM sleep 96.2%; p less than 0.002). These falls represent reductions in arterial oxygen tension similar to those seen in patients with chronic airways obstruction and can be accounted for entirely by the associated reduction in ventilation.     

Oculomotor effects of delta-9-tetrahydrocannabinol in humans: implications for the functional neuroanatomy of the brain cannabinoid system

The significance of cannabinoid signaling for human cognition and motor control is still poorly understood. Here, we have investigated acute behavioral effects of oral delta-9-tetrahydrocannabinol (THC) with oculomotor paradigms in 12 healthy human subjects. Compared to baseline testing: (i) THC increased latencies of reflexive visually guided saccades, while their accuracy was not affected; (ii) latencies of memory-guided saccades were unaffected, but THC modulated accuracy of these eye movements by increasing average gain and gain variability; (iii) frequency of anticipated memory-guided saccades and antisaccade errors was increased; (iv) the saccade amplitude/peak velocity relationships were not affected. These results show that THC acts on selected aspects of saccade control, namely spatial attention shifts, fine tuning of volitional saccades, spatial working memory and inhibition of inappropriate saccades. The pattern of effects suggests modulation of neuronal activity in substantia nigra pars reticulata and/or dorsolateral prefrontal cortex and sparing of the eye fields and the final motor pathway for saccades. Behaviorally, our findings reflect the distribution of CB-1 cannabinoid receptors in the human neocortex, basal ganglia and brainstem and provide evidence for participation of the cannabinoidergic system in high level control of saccades and associated cognitive functions. Saccadic eye movements may provide an objective measure of motor and cognitive effects of cannabinoids.     

Circadian distribution of sleep phases after major abdominal surgery

BACKGROUND: It is believed that the severely disturbed night-time sleep architecture after surgery is associated with increased cardiovascular morbidity with rebound of rapid eye movement (REM). The daytime sleep pattern of patients after major general surgery has not been investigated before. We decided to study the circadian distribution of sleep phases before and after surgery. METHODS: Eleven patients undergoing elective major abdominal surgery were included in the study. Continuous ambulatory polysomnographic monitoring was made 24 h before surgery and 36 h after surgery, thus including two nights after operation. Sleep was scored independently by two blinded observers and the recordings were reported as awake, light sleep (LS, stages I and II), slow wave sleep (SWS, stages III and IV), and REM sleep. RESULTS: There was significantly increased REM sleep (P=0.046), LS (P=0.020), and reduced time awake (P=0.016) in the postoperative daytime period compared with the preoperative daytime period. Five patients had REM sleep during the daytime after surgery. Three of these patients did not have REM sleep during the preceding postoperative night. There was significantly reduced night-time REM sleep for two nights after surgery compared with before surgery (P=0.001). CONCLUSIONS: Patients have significantly increased REM sleep, LS, and reduced time awake during the daytime period after surgery compared with before surgery. Disturbances in the circadian regulation of the sleep-wake cycle may be involved in the development of postoperative sleep disturbances.     

Brain and behavior: a task-dependent eye movement study

Recent electrophysiological and behavioral studies have found similarities in the neurology of pursuit and saccadic eye movements. In a previous study on eye movements using closely matched paradigms for pursuit and saccades, we revealed that both exhibit bimodal distributions of latency to predictable (PRD) and randomized (RND) stimuli; however, the latency to each type of stimulus was different, and there was more segregation of latencies in saccades than pursuit (Burke MR, Barnes GR. 2006. Quantitative differences in smooth pursuit and saccadic eye movements in humans. Exp Brain Res. 175(4):596-608). To investigate the brain areas involved in these tasks, and to search for correlates of behavior, we used functional magnetic resonance imaging during equivalent PRD and RND target presentations. In the contrast pursuit > saccades, which reflects velocity-dependent versus position-dependent activities, respectively, we found higher activation in the dorsolateral prefrontal cortex (DLPFC) for pursuit and in the frontopolar region for saccades. In the contrast RND > PRD, which principally reflects activation related to visually driven versus memory-driven responses, respectively, we found a higher sustained level of activation in the frontal eye fields during visually guided eye movements. The reverse contrast revealed higher activity for the memory-guided responses in the supplementary eye fields and the superior parietal lobe. In addition, we found learning-related activation during the PRD condition in visual area V5, the DLPFC, and the cerebellum.     

Opioid inhibition of rapid eye movement sleep by a specific mu receptor agonist

Patients receiving opioids report feeling sleepy, but opioidsactually inhibit the rapid eye movement phase of sleep (REM).Inhibition of REM sleep is followed by a rebound increase inREM sleep associated with cardiopulmonary complications. Themedial pontine reticular formation (mPRF) is a brain regionfrom which morphine can inhibit REM sleep. The present studytested the hypothesis that specific subtypes of opioid receptorswithin the mPRF mediate inhibition of REM sleep. Synthetic opioidagonists selective for mu, delta and kappa subtypes were microinjectedinto the mPRF of four awake cats and polygraphic recordingsof sleep and breathing were obtained. An enkephalinase inhibitorwas microinjected into the mPRF to assess the contribution ofendogenous opioids to the control of sleep and breathing. Onlythe mu agonist significantly inhibited REM sleep, and no opioiddepressed breathing. These results demonstrate that opioid-inducedREM sleep inhibition is mediated by mu receptor subtypes inthe mPRF.     

Parietal damage dissociates saccade planning from presaccadic perceptual facilitation

A well-known theory in the field of attention today is the premotor theory of attention which suggests that the mechanisms involved in eye movements are the same as those for spatial attention shifts. We tested a parietal damaged patient with unilateral optic ataxia and 4 controls on a dual saccade/attentional task and show a dissociation between saccadic eye movements and presaccadic perceptual enhancement at the saccade goal. Remarkably, though the patient was able to make the appropriate saccades to the left, impaired visual field (undistinguishable from saccades to his right, intact visual field), he was unable to discriminate the letter at the saccade goal (whereas his performance was like controls for letter discrimination in his right visual field). This suggests that saccade planning and presaccadic perceptual facilitation are separable--planning a saccade to a location does not necessitate that the processing of this location is enhanced. Based on these results, we suggest that the parietal cortex is necessary for the coupling between saccade planning and presaccadic perceptual facilitation.     

Dorsal cortical regions subserving visually guided saccades in humans: an fMRI study

Neurophysiological studies in non-human primates have identified saccade-related neuronal activity in cortical regions including frontal (FEF), supplementary (SEF) and parietal eye fields. Lesion and neuroimaging studies suggest a generally homologous mapping of the oculomotor system in humans; however, a detailed mapping of the precise anatomical location of these functional regions has not yet been achieved. We investigated dorsal frontal and parietal cortex during a saccade task vs. central fixation in 10 adult subjects using functional magnetic resonance imaging (fMRI). The FEF were restricted to the precentral sulcus, and did not extend anteriorly into Brodmann area 8, which has traditionally been viewed as their location in humans. The SEF were located in cortex along the interhemispheric fissure and extended minimally onto the dorsal cortical surface. Parietal activation was seen in precuneus and along the intraparietal sulcus, extending into both superior and inferior parietal lobules. These findings localize areas in frontal and parietal cortex involved in saccade generation in humans, and indicate significant differences from the macaque monkey in both frontal and parietal cortex. These differences may have functional implications for the roles these areas play in visuomotor processes.      

A cortico-subcortical model for generation of spatially accurate sequential saccades.

This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments.     

The location probability effects of saccade reaction times are modulated in the frontal eye fields but not in the supplementary eye field

The visual system constantly utilizes regularities that are embedded in the environment and by doing so reduces the computational burden of processing visual information. Recent findings have demonstrated that probabilistic information can override attentional effects, such as the cost of making an eye movement away from a visual target (antisaccade cost). The neural substrates of such probability effects have been associated with activity in the superior colliculus (SC). Given the immense reciprocal connections to SC, it is plausible that this modulation originates from higher oculomotor regions, such as the frontal eye field (FEF) and the supplementary eye field (SEF). To test this possibility, the present study employed theta burst transcranial magnetic stimulation (TMS) to selectively interfere with FEF and SEF activity. We found that TMS disrupted the effect of location probability when TMS was applied over FEF. This was not observed in the SEF TMS condition. Together, these 2 experiments suggest that the FEF plays a critical role not only in initiating saccades but also in modulating the effects of location probability on saccade production.     

Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease.

BACKGROUND--In patients with chronic obstructive pulmonary disease (COPD) periods of hypopnoea occur during rapid eye movement (REM) sleep, but the mechanisms involved are not clear. METHODS--Ten patients with stable COPD were studied during nocturnal sleep. Detailed measurements were made of surface electromyographic (EMG) activity of several respiratory muscle groups and the accompanying chest wall motion using magnetometers. RESULTS--Hypopnoea occurred in association with eye movements during phasic rapid eye movement (pREM) sleep. During pREM sleep there were reductions in EMG activity of the intercostal, diaphragm, and upper airway muscles compared with non-REM sleep. Episodic hypopnoea due to partial upper airway occlusion ("obstructive" hypopnoea) was seen consistently in four subjects while the others showed the pattern of "central" hypopnoea accompanied by an overall reduction in inspiratory muscle activity. Although activity of the intercostal muscles was reduced relatively more than that of the diaphragm, lateral rib cage paradox (Hoover's sign) was less obvious during pREM-related hypopnoea than during wakefulness or non-REM sleep. CONCLUSIONS--Hypopnoea during REM sleep in patients with COPD is associated with reduced inspiratory muscle activity. The pattern of hypopnoea may be either "obstructive" or "central" and is generally consistent within an individual. Relatively unopposed action of the diaphragm on the rib cage during REM sleep is not accompanied by greater lateral inspiratory paradox.     

Nocturnal enuresis and the pontine reticular formation

OBJECTIVES: To assess the previously proposed hypothesis that enuretic patients have a dysfunction in the pontine reticular formation. METHODS: In 18 patients with intractable nocturnal enuresis, rapid eye movement (REM)-related phasic chin muscle activity loss in REM sleep was examined by means of a single-night polysomnography. RESULTS: In 5 of 18 patients, this physiologically seen phenomenon was found to be disturbed. CONCLUSIONS: Since REM-related phasic chin muscle activity loss is disturbed by the functional impairment in the pontine reticular formation, some enuretic patients could be considered as presenting a dysfunction in this structure.     

Study of the relationship between intracranial pressure and paradoxal sleep in the cat (author's transl]

The present study reports on the modification of the intracranial pressure (ICP) during rapid eye movements (REM) sleep in seven chronic cats. 1. REM sleep episodes were characterized by a succession of short lasting (9 +/- 4 seconds) oscillations of the ICP. Peaks amplitude represented a hundred percent increase of the pressure as compared to its resting level. 2. These oscillations either arose from an ICP level similar to that recorded during the preceding slow wave sleep period or were seen to overide a wave of raised ICP that lasted throughout the REM period. 3. Eighty eight percent of the phasic oscillation coincided with a burt of eye movement characteristic of REM sleep. 4. Cerebral pulse wave amplitude can vary for identical ICP mean value in the course of a same REM period.     

Modulation of antisaccades by transcranial magnetic stimulation of the human frontal eye field

It has been suggested that the frontal eye field (FEF), which is involved with the inhibition and generation of saccades, is engaged to a different degree in pro- and antisaccades. Pro- and antisaccades are often assessed in separate experimental blocks. In such cases, saccade inhibition is required for antisaccades but not for prosaccades. To more directly assess the role of the FEF in saccade inhibition and generation, a new paradigm was used in which inhibition was necessary on pro- and antisaccade trials. Participants looked in the direction indicated by a target ('<' or '>') that appeared in the left or right visual field. When the pointing direction and the location were congruent, prosaccades were executed; otherwise antisaccades were required. Saccadic latencies were measured in blocks without and with single pulse transcranial magnetic stimulation (TMS) to the right FEF or a right posterior control site. Results showed that antisaccades generated into the hemifield ipsilateral to the TMS were significantly delayed after TMS over the FEF, but not the posterior control site. This result is interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to disruption of processing in the FEF.     

Oscillatory activity in human parietal and occipital cortex shows hemispheric lateralization and memory effects in a delayed double-step saccade task

We applied magnetoencephalography (MEG) to record oscillatory brain activity from human subjects engaged in planning a double-step saccade. In the experiments, subjects (n = 8) remembered the locations of 2 sequentially flashed targets (each followed by a 2-s delay), presented in either the left or right visual hemifield, and then made saccades to the 2 locations in sequence. We examined changes in spectral power in relation to target location (left or right) and memory load (one or two targets), excluding error trials based on concurrent eye tracking. During the delay period following the first target, power in the alpha (8-12 Hz) and beta (13-25 Hz) bands was significantly suppressed in the hemisphere contralateral to the target. When the second target was presented, there was a further suppression in the alpha- and beta-band power over both hemispheres. In this period, the same sensors also showed contralateral power enhancements in the gamma band (60-90 Hz), most significantly prior to the initiation of the saccades. Adaptive spatial filtering techniques localized the neural sources of the directionally selective power changes in parieto-occipital areas. These results provide further support for a topographic organization for delayed saccades in human parietal and occipital cortex.     

Pontine reference frames for the sensory guidance of movement

The pontine nuclei (PN) are the major intermediary elements in the corticopontocerebellar pathway. Here we asked if the PN may help to adapt the spatial reference frames used by cerebrocortical neurons involved in the sensory guidance of movement to a format potentially more appropriate for the cerebellum. To this end, we studied movement-related neurons in the dorsal PN (DPN) of monkeys, most probably projecting to the cerebellum, executing fixed vector saccades or, alternatively, fixed vector hand reaches from different starting positions. The 83 task-related neurons considered fired movement-related bursts before saccades (saccade-related) or before hand movements (hand movement-related). About 40% of the SR neurons were "oculocentric," whereas the others were modulated by eye starting position. A third of the HMR neurons encoded hand reaches in hand-centered coordinates, whereas the remainder exhibited different types of dependencies on starting positions, reminiscent in general of cortical responses. All in all, pontine reference frames for the sensory guidance of movement seem to be very similar to those in cortex. Specifically, the frequency of orbital position gain fields of SR neurons is identical in the DPN and in one of their major cortical inputs, lateral intraparietal area (LIP).