(1/2544) Frontal cognitive impairments and saccadic deficits in low-dose MPTP-treated monkeys.
There is considerable overlap between the cognitive deficits observed in humans with frontal lobe damage and those described in patients with Parkinson's disease. Similar frontal impairments have been found in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) primate model of Parkinsonism. Here we provide quantitative documentation of the cognitive, oculomotor, and skeletomotor dysfunctions of monkeys trained on a frontal task and treated with low-doses (LD) of MPTP. Two rhesus monkeys were trained to perform a spatial delayed-response task with frequent alternations between two behavioral modes (GO and NO-GO). After control recordings, the monkeys were treated with one placebo and successive LD MPTP courses. Monkey C developed motor Parkinsonian signs after a fourth course of medium-dose (MD) MPTP and later was treated with combined dopaminergic therapy (CDoT). There were no gross motor changes after the LD MPTP courses, and the average movement time (MT) did not increase. However, reaction time (RT) increased significantly. Both RT and MT were further increased in the symptomatic state, under CDoT. Self-initiated saccades became hypometric after LD MPTP treatments and their frequency decreased. Visually triggered saccades were affected to a lesser extent by the LD MPTP treatments. All saccadic parameters declined further in the symptomatic state and improved partially during CDoT. The number of GO mode (no-response, location, and early release) errors increased after MPTP treatment. The monkeys made more perseverative errors while switching from the GO to the NO-GO mode. Saccadic eye movement patterns suggest that frontal deficits were involved in most observed errors. CDoT had a differential effect on the behavioral errors. It decreased omission errors but did not improve location errors or perseverative errors. Tyrosine hydroxylase immunohistochemistry showed moderate ( approximately 70-80%) reduction in the number of dopaminergic neurons in the substantia nigra pars compacta after MPTP treatment. These results show that cognitive and motor disorders can be dissociated in the LD MPTP model and that cognitive and oculomotor impairments develop before the onset of skeletal motor symptoms. The behavioral and saccadic deficits probably result from the marked reduction of dopaminergic neurons in the midbrain. We suggest that these behavioral changes result from modified neuronal activity in the frontal cortex. (+info)
(2/2544) Saccadic performance characteristics and the behavioural neurology of Tourette's syndrome.
OBJECTIVE: To better understand the neuropathological correlates of Tourette's syndrome (TS), measures of saccadic eye movement performance were examined among patients with TS. METHODS: A case-control design was used. Twenty one patients with DSM-IV TS (mean age 40.6 years (SD 11.0); 38% female) mainly recruited from UCSD Psychiatry Services, and a community based sample of 21 normal subjects (mean age 34.6 years (SD 13.4); 43% women) participated in this study. Participants were administered ocular motor tasks assessing visual fixation, and the generation of prosaccades, predictive saccades, and antisaccades. Saccadic reaction time, amplitude, duration, and mean and peak velocity were computed. Intrusive saccades during visual fixation and the proportion of correct antisaccade responses were also evaluated. RESULTS: The groups had similar visual fixation performance. Whereas patients with TS generated prosaccades with normal reaction times and amplitudes, their saccade durations were shorter and their mean velocities were higher than in normal subjects. During a prosaccade gap task, patients with TS exhibited an increased proportion of anticipatory saccades (RTs<90). The proportion of "express" saccades (90
(3/2544) Pontine lesions mimicking acute peripheral vestibulopathy.
OBJECTIVES: Clinical signs of acute peripheral vestibulopathy (APV) were repeatedly reported with pontine lesions. The clinical relevance of such a mechanism is not known, as most studies were biased by patients with additional clinical signs ofbrainstem dysfunction. METHODS: Masseter reflex (MassR), blink reflex (BlinkR), brainstem auditory evoked potentials (BAEPs), and DC electro-oculography (EOG) were tested in 232 consecutive patients with clinical signs of unilateral APV. RESULTS: Forty five of the 232 patients (19.4%) had at least one electrophysiological abnormality suggesting pontine dysfunction mainly due to possible vertebrobasilar ischaemia (22 patients) and multiple sclerosis (eight patients). MassR abnormalities were seen in 24 patients, and EOG abnormalities of saccades and following eye movements occurred in 22 patients. Three patients had BlinkR-R1 abnormalities, and one had delayed BAEP waves IV and V. Clinical improvement was almost always (32 of 34 re-examined patients) associated with improvement or normalisation of at least one electrophysiological abnormality. Brain MRI was done in 25 of the 44 patients and confirmed pontine lesions in six (two infarcts, three inflammations, one tumour). CONCLUSIONS: Pontine dysfunction was suggested in 45 of 232 consecutive patients with clinical signs of APV on the basis of abnormal electrophysiological findings, and was mainly attributed to brainstem ischaemia and multiple sclerosis. The frequency of pontine lesions mimicking APV is underestimated if based on MRI established lesions only. (+info)
(4/2544) Action of the brain stem saccade generator during horizontal gaze shifts. I. Discharge patterns of omnidirectional pause neurons.
Omnidirectional pause neurons (OPNs) pause for the duration of a saccade in all directions because they are part of the neural mechanism that controls saccade duration. In the natural situation, however, large saccades are accompanied by head movements to produce rapid gaze shifts. To determine whether OPNs are part of the mechanism that controls the whole gaze shift rather than the eye saccade alone, we monitored the activity of 44 OPNs that paused for rightward and leftward gaze shifts but otherwise discharged at relatively constant average rates. Pause duration was well correlated with the duration of either eye or gaze movement but poorly correlated with the duration of head movement. The time of pause onset was aligned tightly with the onset of either eye or gaze movement but only loosely aligned with the onset of head movement. These data suggest that the OPN pause does not encode the duration of head movement. Further, the end of the OPN pause was often better aligned with the end of the eye movement than with the end of the gaze movement for individual gaze shifts. For most gaze shifts, the eye component ended with an immediate counterrotation owing to the vestibuloocular reflex (VOR), and gaze ended at variable times thereafter. In those gaze shifts where eye counterrotation was delayed, the end of the pause also was delayed. Taken together, these data suggest that the end of the pause influences the onset of eye counterrotation, not the end of the gaze shift. We suggest that OPN neurons act to control only that portion of the gaze movement that is commanded by the eye burst generator. This command is expressed by driving the saccadic eye movement directly and also by suppressing VOR eye counterrotation. Because gaze end is less well correlated with pause end and often occurs well after counterrotation onset, we conclude that elements of the burst generator typically are not active till gaze end, and that gaze end is determined by another mechanism independent of the OPNs. (+info)
(5/2544) Cortical visuomotor integration during eye pursuit and eye-finger pursuit.
To elucidate cortical mechanisms of visuomotor integration, we recorded whole-scalp neuromagnetic signals from six normal volunteers while they were viewing a black dot moving linearly at the speed of 4 degrees /sec within a virtual rectangle. The dot changed its direction randomly once every 0.3-2 sec. The subject either (1) fixated a cross in the center of the screen (eye fixation task), (2) followed the moving dot with the eyes (eye pursuit task), or (3) followed the dot with both the eyes and the right index finger (eye-finger pursuit task). Prominent magnetic signals, triggered by the changes of the direction of the dot, were seen in all conditions, but they were clearly enhanced by the tasks and were strongest during the eye-finger pursuit task and over the anterior inferior parietal lobule (aIPL). Source modeling indicated activation of aIPL [Brodmann's area (BA) 40], the posterosuperior parietal lobule (SPL; BA 7), the dorsolateral frontal cortex (DLF; BA 6), and the occipital cortex (BA 18/19). The activation first peaked in the occipital areas, then in the aIPL and DLF, and some 50 msec later in the SPL. Our results suggest that all these areas are involved in visuomotor transformation, with aIPL playing a crucial role in this process. (+info)
(6/2544) Role of primate superior colliculus in preparation and execution of anti-saccades and pro-saccades.
We investigated how the brain switches between the preparation of a movement where a stimulus is the target of the movement, and a movement where a stimulus serves as a landmark for an instructed movement elsewhere. Monkeys were trained on a pro-/anti-saccade paradigm in which they either had to generate a pro-saccade toward a visual stimulus or an anti-saccade away from the stimulus to its mirror position, depending on the color of an initial fixation point. Neural activity was recorded in the superior colliculus (SC), a structure that is known to be involved in the generation of fast saccades, to determine whether it was also involved in the generation of anti-saccades. On anti-saccade trials, fixation during the instruction period was associated with an increased activity of collicular fixation-related neurons and a decreased activity of saccade-related neurons. Stimulus-related and saccade-related activity was reduced on anti-saccade trials. Our results demonstrate that the anti-saccade task involves (and may require) the attenuation of preparatory and stimulus-related activity in the SC to avoid unwanted pro-saccades. Because the attenuated pre-saccade activity that we found in the SC may be insufficient by itself to elicit correct anti-saccades, additional movement signals from other brain areas are presumably required. (+info)
(7/2544) Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism.
OBJECTIVE: To investigate the functional integrity of cerebellar and frontal systems in autism using oculomotor paradigms. BACKGROUND: Cerebellar and neocortical systems models of autism have been proposed. Courchesne and colleagues have argued that cognitive deficits such as shifting attention disturbances result from dysfunction of vermal lobules VI and VII. Such a vermal deficit should be associated with dysmetric saccadic eye movements because of the major role these areas play in guiding the motor precision of saccades. In contrast, neocortical models of autism predict intact saccade metrics, but impairments on tasks requiring the higher cognitive control of saccades. METHODS: A total of 26 rigorously diagnosed nonmentally retarded autistic subjects and 26 matched healthy control subjects were assessed with a visually guided saccade task and two volitional saccade tasks, the oculomotor delayed-response task and the antisaccade task. RESULTS: Metrics and dynamics of the visually guided saccades were normal in autistic subjects, documenting the absence of disturbances in cerebellar vermal lobules VI and VII and in automatic shifts of visual attention. Deficits were demonstrated on both volitional saccade tasks, indicating dysfunction in the circuitry of prefrontal cortex and its connections with the parietal cortex, and associated cognitive impairments in spatial working memory and in the ability to voluntarily suppress context-inappropriate responses. CONCLUSIONS: These findings demonstrate intrinsic neocortical, not cerebellar, dysfunction in autism, and parallel deficits in higher order cognitive mechanisms and not in elementary attentional and sensorimotor systems in autism. (+info)
(8/2544) Oculomotor tracking in two dimensions.
Results from studies of oculomotor tracking in one dimension have indicated that saccades are driven primarily by errors in position, whereas smooth pursuit movements are driven primarily by errors in velocity. To test whether this result generalizes to two-dimensional tracking, we asked subjects to track a target that moved initially in a straight line then changed direction. We found that the general premise does indeed hold true; however, the study of oculomotor tracking in two dimensions provides additional insight. The first saccade was directed slightly in advance of target location at saccade onset. Thus its direction was related primarily to angular positional error. The direction of the smooth pursuit movement after the saccade was related linearly to the direction of target motion with an average slope of 0.8. Furthermore the magnitude and direction of smooth pursuit velocity did not change abruptly; consequently the direction of smooth pursuit appeared to rotate smoothly over time. (+info)
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