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)
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)
Heart period and heart period variability during sleep on the MIR space station.
The long-term acclimation of cardiac rhythms to microgravity was studied in four astronauts aboard the Russian space station MIR during wakefulness and sleep. Sleep polygraphies were obtained between the third and the 30th day in space and, in addition, prior to mission on the ground. From each of the sleep polygraphies, beat-to-beat intervals of cardiac rhythms were determined. The response of heart period and heart period variability to the stimulus microgravity was tested during sleep across sleep stages and during waking. A lengthening of heart period by about 100 ms was found in space compared to measurements on the ground. The slowing of heart rate was more pronounced for non-REM sleep than for REM sleep. A systematic change in heart period in relation to the duration of the stay in space could not be detected. An analysis of heart period variability in the high frequency (respiratory sinus arrhythmia) band supports the hypothesis that the decrease of heart rate under microgravity is produced by an increase in parasympathetic activity. Testing the response of cardiac rhythms to microgravity across distinct behavioural states seems to be a powerful tool to investigate the cardiovascular system. (+info)
The relationship between 6-sulphatoxymelatonin and polysomnographic sleep in good sleeping controls and wake maintenance insomniacs, aged 55-80 years.
The pineal hormone, melatonin, is reported to possess hypnotic properties. This has led to an investigation of the relationship between the endogenous melatonin rhythm and sleep. However, this relationship has yet to be fully examined in aged insomniacs and controls. From media advertisements, 16 good sleeping controls (11F, 5M) and 16 sleep maintenance insomniacs (11F, 5M), aged over 55 years, were recruited to participate in a study involving four nights of polysomnographically (PSG) measured sleep followed by a 26 h constant routine. During the constant routine, 2 h urine samples were collected and analysed for the melatonin metabolite, 6-sulphatoxymelatonin (aMT.6S). This was used to determine total melatonin excretion. As well, the following circadian melatonin parameters were calculated from fifth order polynomial curve fitting analyses, the goodness of the polynomial curve fit, peak melatonin concentration, the phase of the melatonin rhythm, and melatonin and sleep rhythm synchrony. Apart for one control, all subjects showed significant circadian melatonin rhythms. Although insomniacs showed a greater amount of wakefulness, less sleep in total, and lower sleep efficiency, no significant group differences were observed in any of the melatonin parameters. In addition, while subjects with more reliable melatonin curve fits showed shorter sleep latencies and higher sleep efficiencies, correlational analyses revealed no other significant relationships between any melatonin and PSG sleep parameters. Overall, the present results suggest that neither melatonin amplitude nor phase are related to sleep quality in the aged. (+info)
The human amygdala plays an important role in gaze monitoring. A PET study.
Social contact often initially depends on ascertaining the direction of the other person's gaze. We determined the brain areas involved in gaze monitoring by a functional neuroimaging study. Discrimination between the direction of gaze significantly activated a region in the left amygdala during eye-contact and no eye-contact tasks to the same extent. However, a region in the right amygdala was specifically activated only during the eye-contact task. Results confirm that the left amygdala plays a general role in the interpretation of eye gaze direction, and that the activity of the right amygdala of the subject increases when another individual's gaze is directed towards him. This suggests that the human amygdala plays a role in reading social signals from the face. (+info)
Interface of epilepsy and sleep disorders.
Obstructive sleep apnoea was first brought to prominence by Henri Gastaut, a French epileptologist. Since that time the interface between epilepsy and sleep disorders has received less attention than might be justified, recognizing that sleep deprivation is a poignant provocateur for seizures. Sleep deprivation is often used as a diagnostic procedure during electroencephalography (EEG) when waking EEG has failed to demonstrate abnormality. Patients referred to an outpatient neurological clinic for evaluation of possible seizures in whom sleep disorder was suspected, either due to snoring during the EEG or based on history, were evaluated with all-night diagnostic polysomnography (PSG) and appropriate intervention administered as indicated. Patient and seizure demography, sleep disorder and response to therapy were reviewed and the interface explored. Fifty patients aged between 10 and 83 years underwent PSG. Approximately half were diagnosed with epilepsy and almost three-quarters had sleep disorders sufficiently intrusive to require therapy (either continuous positive air pressure (CPAP) or medication). With co-existence of epilepsy and sleep disorders, proper management of sleep disorders provided significant benefit for seizure control. Snoring during EEG recordings could alert to the possibility of a sleep disorder even with epilepsy diagnosed. Where both epilepsy and sleep disorder coexist appropriate management of the sleep disorder improves control of the epilepsy. (+info)
Characteristics of simian adaptation fields produced by behavioral changes in saccade size and direction.
The gain of saccadic eye movements can be altered gradually by moving targets either forward or backward during targeting saccades. If the gain of saccades to targets of only one size is adapted, the gain change generalizes or transfers only to saccades with similar vectors. In this study, we examined the spatial extent of such saccadic size adaptation, i.e., the gain adaptation field. We also attempted to adapt saccade direction by moving the target orthogonally during the targeting saccade to document the extent of a direction or cross-axis adaptation field. After adaptive gain decreases of horizontal saccades to 15 degrees target steps, >82% of the gain reduction transferred to saccades to 25 degrees horizontal target steps but only approximately 30% transferred to saccades to 5 degrees steps. For the horizontal component of oblique saccades to target steps with 15 degrees horizontal components and 10 degrees upward or downward vertical components, the transfer was similar at 51 and 60%, respectively. Thus the gain decrease adaptation field was quite asymmetric in the horizontal dimension but symmetric in the vertical dimension. Although gain increase adaptation produced a smaller gain change (13% increase for a 30% forward adapting target step) than did gain decrease adaptation (20% decrease for a 30% backward adapting target step), the spatial extent of gain transfer was quite similar. In particular, the gain increase adaptation field displayed asymmetry in the horizontal dimension (58% transfer to 25 degrees saccades but only 32% transfer to 5 degrees saccades) and symmetry in the vertical direction (50% transfer to the horizontal component of 10 degrees upward and 40% transfer to 10 degrees downward oblique saccades). When a 5 degrees vertical target movement was made to occur during a saccade to a horizontal 10 degrees target step, a vertical component gradually appeared in saccades to horizontal targets. More than 88% of the cross-axis change in the vertical component produced in 10 degrees saccades transferred to 20 degrees saccades but only 12% transferred to 4 degrees saccades. The transfer was similar to the vertical component of oblique saccades to target steps with either 10 degrees upward (46%) or 10 degrees downward (46%) vertical components. Therefore both gain and cross-axis adaptation fields have similar spatial profiles. These profiles resemble those of movement fields of neurons in the frontal eye fields and superior colliculus. How those structures might participate in the adaptation process is considered in the DISCUSSION. (+info)
Rhythmic neuronal activity in the lateral cerebellum of the cat during visually guided stepping.
1. The discharge patterns of 117 lateral cerebellar neurones were studied in cats during visually guided stepping on a horizontal circular ladder. Ninety per cent of both nuclear cells (53/59) and Purkinje cells (53/58) showed step-related rhythmic modulations of their discharge frequency (one or more periods of 'raised activity' per step cycle of the ipsilateral forelimb). 2. For 31% of nuclear cells (18/59) and 34% of Purkinje cells (20/58) the difference between the highest and lowest discharge rates in different parts of the step cycle was > 50 impulses s-1. 3. Individual neurones differed widely in the phasing of their discharges relative to the step cycle. Nevertheless, for both Purkinje cells and nuclear cells population activity was significantly greater in swing than in stance; the difference was more marked for the nuclear population. 4. Some cells exhibited both step-related rhythmicity and visual responsiveness (28 of 67 tested, 42%), whilst others were rhythmically active during locomotion and increased their discharge rate ahead of saccadic eye movements (11 of 54 tested, 20%). The rhythmicity of cells that were visually responsive was typical of the rhythmicity seen in the whole locomotor-related population. The step-related rhythmicity of cells that also discharged in relation to saccades was generally below average strength compared with the cortical and nuclear populations as a whole. 5. The possibility is discussed that the rhythmicity of dentate neurones acts as a powerful source of excitatory locomotor drive to motor cortex, and may thereby contribute to establishing the step-related rhythmicity of motor cortical (including pyramidal tract) neurones. More generally, the activity patterns of lateral cerebellar neurones provide for a role in the production of visually guided, co-ordinated eye and body movements. (+info)