Serological survey of Bartonella spp., Borrelia burgdorferi, Brucella spp., Coxiella burnetii, Francisella tularensis, Leptospira spp., Echinococcus, Hanta-, TBE- and XMR-virus infection in employees of two forestry enterprises in North Rhine-Westphalia, Germany, 2011-2013.

We initiated a survey to collect basic data on the frequency and regional distribution of various zoonoses in 722 employees of forestry enterprises in the German state of North Rhine-Westphalia (NRW) from 2011 to 2013. Exposures associated with seropositivity were identified to give insight into the possible risk factors for infection with each pathogen. 41.2% of participants were found to be seropositive for anti-Bartonella IgG, 30.6% for anti-Borrelia burgdorferi IgG, 14.2% for anti-Leptospira IgG, 6.5% for anti-Coxiella burnetii IgG, 6.0% for anti-Hantavirus IgG, 4.0% for anti-Francisella tularensis IgG, 3.4% for anti-TBE-virus IgG, 1.7% for anti-Echinococcus IgG, 0.0% for anti-Brucella IgG and anti-XMRV IgG. Participants seropositive for B. burgdorferi were 3.96 times more likely to be professional forestry workers (univariable analysis: OR 3.96; 95% CI 2.60-6.04; p<0.001); and participants seropositive for Hantavirus 3.72 times more likely (univariable analysis: OR 3.72; 95% CI 1.44-9.57; p=0.007). This study found a surprisingly high percentage of participants seropositive for anti-B. henselae IgG and for anti-F. tularensis IgG. The relatively high seroprevalence for anti-Leptospira IgG seen in this study could be related to living conditions rather than to exposure at work. No specific risk for exposure to C. burnetii and Echinococcus was identified, indicating that neither forestry workers nor office workers represent a risk population and that NRW is not a typical endemic area. Forestry workers appear to have higher risk for contact with B. burgdorferi-infected ticks and a regionally diverse risk for acquiring Hantavirus-infection. The regional epidemiology of zoonoses is without question of great importance for public health. Knowledge of the regional risk factors facilitates the development of efficient prevention strategies and the implementation of such prevention measures in a sustainable manner.

Distributed representations of the "preparatory set" in the frontal oculomotor system: a TMS study.

BACKGROUND: The generation of saccades is influenced by the level of "preparatory set activity" in cortical oculomotor areas. This preparatory activity can be examined using the gap-paradigm in which a temporal gap is introduced between the disappearance of a central fixation target and the appearance of an eccentric target. METHODS: Ten healthy subjects made horizontal pro- or antisaccades in response to lateralized cues after a gap period of 200 ms. Single-pulse transcranial magnetic stimulation (TMS) was applied to the dorsolateral prefrontal cortex (DLPFC), frontal eye field (FEF), or supplementary eye field (SEF) of the right hemisphere 100 or 200 ms after the disappearance of the fixation point. Saccade latencies were measured to probe the disruptive effect of TMS on saccade preparation. In six individuals, we gave realistic sham TMS during the gap period to mimic auditory and somatosensory stimulation without stimulating the cortex. RESULTS: TMS to DLPFC, FEF, or SEF increased the latencies of contraversive pro- and antisaccades. This TMS-induced delay of saccade initiation was particularly evident in conditions with a relatively high level of preparatory set activity: The increase in saccade latency was more pronounced at the end of the gap period and when participants prepared for prosaccades rather than antisaccades. Although the "lesion effect" of TMS was stronger with prefrontal TMS, TMS to FEF or SEF also interfered with the initiation of saccades. The delay in saccade onset induced by real TMS was not caused by non-specific effects because sham stimulation shortened the latencies of contra- and ipsiversive anti-saccades, presumably due to intersensory facilitation. CONCLUSION: Our results are compatible with the view that the "preparatory set" for contraversive saccades is represented in a distributed cortical network, including the contralateral DLPFC, FEF and SEF.

Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17).

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is associated with an expansion of CAG/CAA trinucleotide repeats in the gene encoding the TATA-binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity. METHODS: Eye movements (saccades, smooth pursuit) of 15 SCA17 mutation carriers (mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age-matched control subjects using the video-based two-dimensional EYELINK II system. RESULTS: Smooth pursuit initiation (step-ramp paradigm) and maintenance were strongly impaired, i.e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch-up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze-evoked nystagmus was found in one-third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades (52%) and memory-guided saccades (42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration. CONCLUSIONS: Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging (morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e.g., dementia and parkinsonism.

Functional dissociation of saccade and hand reaching control with bilateral lesions of the medial wall of the intraparietal sulcus: implications for optic ataxia.

The posterior parietal cortex (PPC) is essential for the integration of visuomotor information during visually guided reaching. Studies in macaque monkeys have demonstrated a functional specialisation around the intraparietal sulcus (IPS) with a more medial representation of hand movements ("parietal reach region") and a more lateral representation of saccadic eye movements (lateral intraparietal area, LIP). Here we present evidence for the validity of this concept with respect to the human parietal cortex. We recorded isolated and combined goal-directed eye-hand movements in normal control subjects and in a patient with bilateral parieto-occipital lesions and incomplete Balint's syndrome including severe optic ataxia (misreaching to visual targets). Brain lesions in the patient were caused by acute posterior leucoencephalopathy in association with aortic surgery because of Takayasu's arteritis. MRI scans showed bilateral line-shaped hemorrhagic lesions, restricted to the cortex at the medial banks of the intraparietal sulcus, but leaving its lateral banks largely intact. In the patient visually guided reaching was significantly dysmetric, whereas the metrics of visually guided saccades were within normal limits. Dysmetria was more pronounced for the right visual field, with a gross hypermetria. Variability of the movement improved when a delay of 5 or 10 s was introduced between target presentation and movement execution. Lesion data support the concept of a functional specialisation around the human IPS: The cortex medial to the IPS predominantly controls rapid goal-directed reaching movements, comparable to the parietal reach region in monkeys, whereas saccadic eye movements appear to be controlled rather by the cortex lateral to the IPS.

Three-dimensional cytoarchitectonic analysis of the posterior bank of the human precentral sulcus.

Studies employing functional magnetic resonance imaging have identified the human frontal eye field as being in the anterior and partly in the posterior wall, as well as at the base of the precentral sulcus. Moreover, it is known that the frontal eye field extends rostrally to the superior frontal sulcus. According to Brodmann's cytoarchitectonic map, this region belongs to the dysgranular Brodmann area 6 of the premotor cortex. However, the frontal eye field in non-human primates has been located within the arcuate sulcus in Brodmann area 8, generating considerable debate about where to locate exactly the frontal eye field in humans. Functional studies of the primate frontal eye field have revealed a principal homology of voluntary saccadic control systems in human and old-world monkeys, especially the macaque. But these homologies seem to be contradicted by the reported topographic localization at the cytoarchitectonic level. Therefore, we studied the cytoarchitectonic structure of the posterior bank of the precentral sulcus of a human brain, employing newly developed spatial mapping techniques to provide data about whether or not this region should be considered cytoarchitecturally homogeneous or heterogeneous. We used functional magnetic resonance imaging results, as an initial guide in localizing a region which is activated by saccadic tasks. A maximum of activation was detected around the junction of the superior frontal sulcus and the precentral sulcus extending 1.5 cm along the precentral sulcus in direction of the lateral sulcus. Here, one human brain has been analyzed to obtain preliminary data about the cytoarchitectonical changes of a part of area 6. Statistical analysis of the three-dimensional architectonic data from this region allowed us to identify a zone at the posterior bank, which in other studies has been associated with a functional region that controls pursuit eye movements and performs sensory-to-motor transformations. We found two significant sectors along the ventral part of the posterior bank of the precentral sulcus. The caudal transition region coincides partly with a region that integrates retinal and eye position signals for target location, arm, and axial movements. The second more ventrally located region is attributed to process oral-facial movements. The caudal transition region coincides with our functional magnetic resonance imaging investigation. It was revealed that this region lies at the inferior frontal eye field, where a pronounced activation over a larger region can be stimulated. Currently, more studies are needed to combine functional magnetic resonance imaging data of maximal activation with data from whole histologic brain sections of more individuals and to quantify the variability of this region and its sub-regions by means of a standardized brain atlas.

[Hallucinations in Parkinson's disease]. / Halluzinationen beim Morbus Parkinson.

The appearance of psychiatric symptoms is not rare in the course and treatment of Parkinson's disease. In particular, therapy with L-dopa or dopamine agonists leads to increased dream activity. As with sleep disturbances, this can be a warning signal of paranoid hallucinatory psychosis.However, isolated visual hallucinations before manifest psychosis in Parkinson's must generally be regarded as resulting from medication. They occur in up to 30% of Parkinson's patients and often involve visual and figurative hallucinations. Visual hallucinations most probably result from the combined effect on dopaminergic and serotonergic systems in the CNS. Therapy consists in normalization of H(2)O and electrolyte levels, control of the accompanying medication, reduction of the evening doses of anti-Parkinson's medications, and serotonin antagonists such as clozapine.

Visual search in patients with left visual hemineglect.

In patients with hemi-spatial neglect eye movement patterns during visual search reflect not only inattention for the contralesional hemi-field, but interacting deficits of multiple visuo-spatial and cognitive functions, even in the ipsilesional hemi-field. Evidence for these deficits is presented from the literature and from saccadic scan-path analysis during feature and conjunction search in 10 healthy subjects and in 10 patients with manifest or recovered left visual neglect due to right-hemispheric stroke. Deficits include (1) a rightward shift of spatial representation, (2) deficient spatial working memory and failure of systematic search strategies, leading to multiple re-fixations, more after frontal lesions, and (3) a reduced spotlight of attention and a deficient pop-out effect of color, more after temporo-parietal lesions.

Convergence retraction nystagmus: a disorder of vergence?

The pathological mechanism of convergence retraction nystagmus (CRN) is not known. To determine whether CRN is a disorder of vergence or of the saccadic system, the scleral search coil technique was used to record binocularly the three-dimensional components of CRN in a patient with a left mesencephalic infarction involving the nucleus of the posterior commissure and the rostral interstitial nucleus of the medial longitudinal fascicle. CRN had disconjugate horizontal and torsional components. The horizontal amplitude/velocity relationship of CRN aligned with the main sequence of vergence responses of normal control subjects but not with that of saccades. Vergence responses of the right eye and left eye were not asynchronous. The slow phases of CRN showed an exponential decay with a time constant of 70 milliseconds. Thus, CRN is probably a disorder of vergence rather than of opposing adducting saccades.

Activation of frontoparietal cortices during memorized triple-step sequences of saccadic eye movements: an fMRI study.

To determine the cortical areas controlling memory-guided sequences of saccadic eye movements, we performed functional magnetic resonance imaging (fMRI) in six healthy adults. Subjects had to perform a memorized sequence of three saccades in darkness, after a triple-step stimulus of successively flashed laser targets. To assess the differential contribution of saccadic subfunctions, we applied several control conditions, such as central fixation with or without triple-step visual stimulation, self-paced saccades in darkness, visually guided saccades and single memory-guided saccades. Triple-step saccades strongly activated the regions of the frontal eye fields, the adjacent ventral premotor cortex, the supplementary eye fields, the anterior cingulate cortex and several posterior parietal foci in the superior parietal lobule, the precuneus, and the middle and posterior portion of the intraparietal sulcus, the probable location of the human parietal eye field. Comparison with the control conditions showed that the right intraparietal sulcus and parts of the frontal and supplementary eye fields are more involved in the execution of triple-step saccades than in the other saccade tasks. In accordance with evidence from clinical lesion studies, we propose that the supplementary eye field essentially controls the triggering of memorized saccadic sequences, whereas activation near the middle portion of the right intraparietal sulcus appears to reflect the necessary spatial computations, including the use of extraretinal information (efference copy) about a saccadic eye displacement for updating the spatial representation of the second or third target of the triple-step sequence.

Lateralized EEG components with direction information for the preparation of saccades versus finger movements.

During preparation of horizontal saccades in humans, several lateralized (relative to saccade direction), event-related EEG components occur that have been interpreted as reflecting activity of frontal and parietal eye fields. We investigated to what degree these components are specific to saccade preparation. EEG lateralization was examined within the interval (1 s) between a first (S1) and a second (S2) stimulus, after which a response had to be made (look left or right, or press a button with the left or right index finger). The visual S1 indicated either the direction (left vs right) and/or the effector (eye vs finger), and S2 (visual/auditory in different blocks) added the information not given by S1. An occipital component (220 ms after S1) was effector-independent, probably reflecting processing of the direction code. The following parietotemporal component (320 ms after S1) was specific for direction information. This component seems more relevant for finger movements than for saccades and may reflect a link between visual perception to action. A later frontal component (480 ms after S1) was specific for direction information and may be related to the planning of a lateral movement. One component was entirely specific for the preparation of a finger movement (the lateralized readiness potential before S2). Thus, several different lateralized processes in the S1-S2 interval could be delineated, reflecting hand-specific preparation, processing of the direction code, and the coordination of perception and action, but no components were observed as being specific for saccade preparation.

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.

Slow EEG potentials (contingent negative variation and post-imperative negative variation) in schizophrenia: their association to the present state and to Parkinsonian medication effects.

Between warning signal (S1) and imperative signal (S2), the EEG shifts negatively (contingent negative variation, CNV) reflecting preparation and expectancy. Reduced CNV and continued negativity after S2 (post-imperative negative variation, PINV) have been repeatedly found in schizophrenic patients and have been interpreted as a deficit in attentional processes (CNV) and as uncertainty about the correctness of one's own response to the S2 (PINV). Recent studies obtained a CNV reduction specifically at central sites but not at frontal ones. The present study investigated whether these alterations of slow negative potentials depend on present state of symptoms, on the particular task used, and on neuroleptic medication. Therefore, out-patients and in-patients were studied, two different S1-S2 tasks were used, and the control groups were healthy subjects and patients with Parkinson's disease. The central CNV reduction was stable across tasks and across in-patients and outpatients. Frontal CNV was reduced in in-patients but in only one of the two tasks in outpatients. The schizophrenic patients' enhanced PINV was larger contralaterally than ipsilaterally to the responding hand, correlated with medication, and occurred in similar way in patients with Parkinson's disease. Thus, the PINV increase might reflect the Parkinsonian side effects of the anti-psychotic medication. In contrast, the central CNV reduction appears as a stable marker of schizophrenia, the frontal CNV reduction as a state-dependent effect. The central CNV reduction might reflect impairment in forming stable stimulus-response associations, the relative frontal enhancement might reflect the out-patients' attempt at compensating that impairment.

Combined deficits of saccades and visuo-spatial orientation after cortical lesions.

Functionally, saccadic eye movements are closely linked to visuo-spatial orientation. Anatomically, the network of cortical areas controlling saccades also seems to be involved in spatial attention and orientation. Consequently, lesions should cause deficits in both categories. We investigated this in 34 patients with focal unilateral lesions of the posterior parietal cortex (PPC), the frontal eye fields (FEF), the supplementary motor area (SMA), or the dorsolateral prefrontal cortex (PFC). Saccadic eye movements were recorded using infrared reflection oculography. Visual hemineglect or other visuo-spatial disorders were investigated by a series of standardized paper-pencil tests. Further, the internal spatial coordinates (subjective visual vertical and subjective straight ahead) were assessed psychophysically. Depending on the site of the lesion, different patterns of deficits were identified: lesions of the PPC impaired reflexive exploration of visual space in terms of delayed and hypometric visually triggered saccades into the contralesional hemifield, related to the severity of visual hemineglect. Further, PPC lesions specifically affected basic functions of the perceptual analysis of space, such as the internal spatial coordinates and spatial constancy across saccades. The latter was tested by applying visual double-step stimuli, where saccade-related extraretinal information had to be taken into account for achieving spatial accuracy. Frontal lesions left these functions intact. FEF lesions, however, impaired systematic intentional exploration of space, thus causing an exploratory-motor type of visual hemineglect. Prefrontal (PFC) lesions impaired the working memory for saccade-related spatial information, and SMA lesions affected temporal properties such as the timing of saccadic sequences, but did not cause specific visuo-spatial deficits. In conclusion, patients with frontal or parietal cortical lesions often exhibit combined saccadic and visuo-spatial disorders, most of which are topically specific.

Lateralized human cortical activity for shifting visuospatial attention and initiating saccades.

Lateralized human cortical activity for shifting visuospatial attention and initiating saccades. J. Neurophysiol. 80: 2900-2910, 1998. The relation between shifts of visual attention and saccade preparation was investigated by studying their electrophysiological correlates in human scalp-recorded electroencephalogram (EEG). Participants had to make saccades either to a saliently colored or to a gray circle, simultaneously presented in opposite visual hemifields, under different task instructions. EEG was measured within the short interval between stimulus onset and saccade, focusing on lateralized activity, contralateral either to the side of the relevant stimulus or to the direction of the saccade. Three components of lateralization were found: 1) activity contralateral to the relevant stimulus irrespective of saccade direction, peaking 250 ms after stimulus onset, largest above lateral parietal sites, 2) activity contralateral to the relevant stimulus if the stimulus was also the target of the saccade, largest 330-480 ms after stimulus onset, widespread over the scalp but with a focus again above lateral parietal sites, and 3) activity contralateral to saccade direction, beginning about 100 ms before the saccade, largest above mesial parietal sites, with some task-dependent fronto-central contribution. Because of their sensitivity to task variables, component 1 is interpreted as the shifting of attention to the relevant stimulus, component 2 is interpreted as reflecting the enhancement of the attentional shift if the relevant stimulus is also the saccade target, and component 3 is interpreted as the triggering signal for saccade execution. Thus human neurophysiological data provided evidence both for independent and interdependent processes of saccade preparation and shifts of visual attention.

Visually induced reactivity in posterior cerebral artery blood flow.

To evaluate visually induced reactivity (VIR) in the posterior cerebral artery (PCA), mean flow velocities in the PCA were measured bilaterally in 35 normal subjects and in 17 patients with PCA territory infarctions, by means of transcranial Doppler ultrasound. After the individual PCA baseline flow was estimated, different visual stimuli were applied: on-off light, colored light, complex scene, and visual imagery task, and the CO2 test was administered. A sampling rate of 20 Hz was used, and the raw data were transferred to a computer. The baseline flow and the maximum flow increase were calculated with a specially designed program. In control subjects, the on-off light stimulus induced a mean increase in PCA flow velocities of 21.5+/-6.4%, and colored light induced an increase of 22.3+/-6.3%. Complex scenes significantly elevated VIR more than light and colored light, with a mean increase of 28.8+/-6.8% (p < 0.05). Mental imagery had no significant effect on PCA flow velocities. There was no significant difference in flow between the right and left PCA in healthy subjects. In patients with PCA territory infarctions with homonymous hemianopsia or quadrantanopsia, there was a marked decrease of VIR and CO2 reactivity on the affected side corresponding to the extent of PCA territory infarction. Visual stimuli increased blood flow velocity bilaterally in the PCA, which supply the visual cortex and visual association area. This noninvasive test seems to be well suited to normal subjects and to patients with vascular disorders affecting the PCA.