[Cognitive functions of the prefrontal cortex: neuroscience and clinic]. / Kognitive Hirnleistungen des präfrontalen Kortex : Neurowissenschaft und Klinik.

Basic neuroscientific research has greatly contributed to a deeper understanding of the cognitive functions of the prefrontal cortex (PFC). Injuries of the PFC typically give rise to severe cognitive disorders that usually are subsumed under the broad rubric of executive dysfunctions (EDF). The umbrella term of EDF denotes a high-level disorder in the control of thought and action. The existence of EDF is of critical importance for the prognosis of disabilities in daily living, vocational rehabilitation, and social integration. Neuropsychological assessment instruments and intervention programs are discussed.

[Crossed aphasia or dysexecutive syndrome? A case report]. / Gekreuzte Aphasie oder Dysexekutives Syndrom? Ein Fallbericht

The case of a female dextral patient (MN) is reported. MN sustained a partial frontotemporal infarction in the right hemisphere. Clinically, MN presented herself mainly with aphasic symptoms. The dextrality of the patient and the laterality of the lesion as well as the nature of language deficits would legitimate the diagnosis of a crossed aphasia, implying paradoxical lateralization of language in MN. However, comprehensive neuropsychological assessment revealed the presence of a global dysexecutive syndrome in MN, suggesting a general cognitive impairment, part of which must be the aphasic symptoms. General issues regarding the relationship between language and cognition and the lateralization of cognitive functions are discussed.

Deficits of smooth pursuit initiation in patients with degenerative cerebellar lesions.

It is well known that cerebellar dysfunction can lead to an impairment of eye velocity during sustained pursuit tracking of continuously moving visual target. We have now studied the initiation of smooth pursuit eye movements towards predictable and randomized visual step-ramp stimuli in six patients with degenerative cerebellar lesions and six age-matched healthy controls using the magnetic scleral search-coil technique. In comparison with the control subjects, the cerebellar patients showed a significant delay of pursuit onset, and their initial eye acceleration was significantly decreased. These cerebellar deficits of pursuit initiation were similarly found in response to both randomized and predictable step-ramps, suggesting that predictive input does not compensate for cerebellar deficits in the initiation period of smooth pursuit. When we compared initial saccades during smooth tracking of foveofugal and foveopetal step-ramps, the absolute position error of these saccades did not significantly differ between patients and controls. In fact, none of the patients showed any bias of the saccadic position error that was related to the direction or velocity of the ongoing target motion. This work presents further evidence that the effect of cerebellar degeneration is not limited to the impaired velocity gain of steady-state smooth pursuit. Instead, it prolongs the processing time required to initiate smooth pursuit and impairs the initial eye acceleration. These two deficits were not associated with an abnormal assessment of target velocity and they were not modified by predictive control mechanisms, suggesting that cerebellar deficits of smooth initiation are not primarily caused by abnormal information on target motion being relayed to the cerebellum.

Oculomotor testing in the differential diagnosis of degenerative ataxic disorders.

BACKGROUND: Oculomotor abnormalities have been reported in patients with degenerative ataxic disorders. OBJECTIVE: To assess the diagnostic sensitivity and specificity of oculomotor deficits in patients with Friedreich ataxia (FA), cerebellar atrophy (CA), and olivopontocerebellar atrophy (OPCA). SETTING: Neurology clinic at a university hospital in Lübeck, Germany. PATIENTS: Seven patients with FA, 9 with CA, and 10 with OPCA were studied. These patients were selected from an ongoing follow-up study. MAIN OUTCOME MEASURES: Eye movements were recorded by electro-oculography; an extensive battery of quantitative tests was used. RESULTS: A proven CAG repeat expansion on chromosome 6 or 14 was significantly associated with reduced saccadic eye velocity and vertical gaze palsy (P<.001, Mann-Whitney U test). All 6 patients with OPCA and slow saccades had an autosomal-dominant inheritance; 4 of them were proved to have spinocerebellar atrophy type 1. In 9 of these patients (4 with FA, 1 with CA, and 4 with OPCA), the genetic defect could not be identified. Saccadic dysmetria, impairment of smooth pursuit and optokinetic nystagmus, deficient suppression of the vestibulo-ocular reflex by either visual or otolith input, and pathological nystagmus were attributed to degenerative lesions in different parts of the cerebellum. However, these symptoms failed to clearly distinguish between the different groups of patients, whereas decreased vestibulo-ocular reflex gain, slow saccades, and vertical gaze palsy pointed to an extracerebellar manifestation of the degenerative disease, occurring only in patients with OPCA and FA. CONCLUSIONS: In this prospective study, oculomotor disturbances were mainly related to cerebellar dysfunction. Only a few of them were caused by extracerebellar manifestations of the disease, such as slowing of saccades, which was characteristic for patients with OPCA of autosomal-dominant inheritance.

Anticipatory smooth eye movements of high velocity triggered by large target steps: normal performance and effect of cerebellar degeneration.

We studied frequencies and dynamic characteristics of anticipatory smooth eye movements (ASEM) in humans who were tracking step target movements of 20-70 deg amplitude. During presentation of periodic steps of constant amplitude healthy subjects showed frequent high velocity ASEM reaching maximal peak velocities of 5-40 deg/sec. There was no effect of ASEM on the frequency of anticipatory saccades. Randomization of target step amplitude or onset reduced the frequency of ASEM but did not completely abolish fast ASEM. In patients with cerebellar degeneration who exhibited impaired smooth pursuit, fast ASEM were absent and the number of slow ASEM was minimal. In conclusion, large sequential target steps can elicit much higher ASEM velocities than typically described in the literature. Similar to slow ASEM triggered by small steps, these fast ASEM do not require specific training and are not canceled by unpredictable step target motion. However, fast ASEM depend on the intact function of the cerebellum which gives further evidence of their generation by the smooth pursuit oculomotor subsystem.

Age-related changes in visual tracking.

BACKGROUND: To reassess conflicting findings in earlier studies on the effect of aging on smooth pursuit and saccadic eye movements, we compared visual tracking in a large number of elderly normal subjects aged 75 to 93 years and a group of young adults aged 18 to 43 years. METHODS: Saccades and smooth pursuit were induced by a laser target projected onto a screen. Eye movements were recorded with electrooculography and analyzed with a digital computer. RESULTS: Smooth pursuit gain was significantly decreased at all target velocities in the older subjects, and the difference between young and old increased with increasing target velocity and acceleration. Peak saccade velocity was significantly slower for amplitudes exceeding 20 degrees, and saccadic reaction times were prolonged in older subjects compared with younger subjects. Mean saccade accuracy was not significantly different between age groups. Within tests, variability increased with aging for smooth pursuit, saccadic reaction time, and saccadic accuracy measurements. CONCLUSION: The increased intratest variability in older subjects probably resulted from nonspecific changes in alertness and attention commonly occurring with aging, whereas the decreased gain of smooth pursuit and saccades with increasing stimulus magnitude most likely resulted from age-related neural degeneration in specific visuomotor pathways.

Comparison of oculomotor findings in the progressive ataxia syndromes.

In this study we compare the results of quantitative oculomotor function testing in patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA) and cerebello-olivary atrophy (CA). Common features in all three syndromes included gaze-evoked nystagmus, saccade dysmetria and prolonged saccade reaction times. Patients with FA showed a characteristic combination of frequent saccadic intrusions, especially ocular flutter, relatively preserved optokinetic nystagmus (OKN) and smooth pursuit, and impaired vestibulo-ocular reflex (VOR) responses. In patients with CA saccadic intrusions were infrequent, OKN and smooth pursuit were severely impaired and VOR gain was normal or increased. Results in OPCA were more variable. When present, slowing of saccades or the combined loss of pursuit and vestibular function were characteristic for OPCA. The ability to suppress the VOR with a head fixed target was relatively preserved in FA, normal to moderately impaired in OPCA and always severely impaired in CA. We conclude that oculomotor testing is useful in the differential diagnosis of the progressive ataxia syndromes.

Preview control of gaze saccades: efficacy of prediction modulates eye-head interaction during human gaze saccades.

Healthy human subjects made orienting saccades towards visual target stimuli, either with the head fixed or during intended time optimal head movements. Four experimental paradigms were used to study the influence of target predictability on eye-head coordination. They represented different sequences of horizontal target steps, that were varied in amplitude, direction and frequency. In some subjects midflight perturbations of the active head movements were applied to examine the intrasaccadic vestibulo-ocular reflex (VOR). In coordinated gaze saccades, latencies and dynamics of the eye saccade and the additional head trajectory demonstrated specific task-related changes with respect to the head fixed condition. Highly predictable target steps result in the relatively earlier onset of the head movement and an increase of the intrasaccadic head contribution to the overall gaze displacement. Differences in the level of VOR suppression became significant when gaze amplitudes exceeded 60 degrees. Consequently, an effective speed up of large gaze saccades was found with increased target predictability. We concluded, that eye-head coordination during human gaze saccades underlies high level preview control mechanisms. A parametric modulation of the intrasaccadic VOR maintains gaze accuracy, although the actual contribution of the more flexible head motor system varied, depending on gaze amplitude and prediction. The efficacy of preview control depends on interaction of these factors.

Effects of prolonged cold injury on the subcutaneous microcirculation of the hamster. I. Technique, morphology and tissue oxygenation.

An animal model is described allowing for direct measurements of local tissue PO2, microhemodynamics and vascular density in the event of a prolonged non freezing cold injury. The model consists of implanting a transparent skin fold chamber in the dorsal skin fold in hamsters and of inserting two permanent indwelling catheters in jugular vein and carotid artery, respectively. The microcirculation was studied using a Wild Photomacroscope for photography and a platinum multiwire electrode for measurements of local PO2 in the conscious animal. After 72 h of recovery from anesthesia and surgery, the experimental was started with the animal immobilized. The decrease of local s.c. temperature was achieved by perfusing a heat exchanger with distilled H2O and Isopropanol 70% (1:1) at a rate of 81/min with the heat exchanger located directly beneath the aluminium frame of the chamber. With this technique, a decrease in local tissue temperature from 28 degrees C to 15 degrees C could be obtained within 15 min and was kept constant for 60 min. After photography of the microcirculation and local PO2-measurements, the local temperature was further reduced to 5 degrees C with 15 min. Sixty minutes later, the area exposed was slowly rewarmed from a level of 5 degrees C within 30 min. This procedure was repeated in intervals of 24 h over a period of five days. During the course of the experiments, local PO2 values shifted toward hypoxic or even anoxic values. Intravital microscopic observation revealed aggregate formation, stasis and obstruction of capillary flow associated with pronounced tissue anoxia after five cold exposures. This event resulted inevitably in tissue necrosis and scar formation after seven consecutive exposures to cold. It is concluded that this model can be used to study the effects of local non freezing cold injury in a precisely reproducible manner.