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Background: The excellent fungicidal activity of [1,2,4]triazolo[1,5-a]pyrimidines suggested the search for further analogues with improved properties., Results: A series of novel trisubstituted pyrido[2,3-b]pyrazines has been designed and prepared as 6,6-biheterocyclic analogues of related 5,6-bicyclic [1,2,4]triazolo[1,5-a]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter (Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr (Pyricularia oryzae Cav., rice blast). Structure-activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8., Conclusion: 8-Amino-7-aryl-6-halogen-substituted pyrido[2,3-b]pyrazines have been prepared as 6,6-biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four-step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [(R)-(1,2-Dimethylpropyl)]-[6-fluoro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazin-8-yl]amine showed excellent activity against three economically important phytopathogens.

Aims: It was investigated whether the cortical activity during tasks requiring focused or divided attention is reduced in multiple sclerosis patients with prominent deficits (MS(+D)) and increased in patients without impairment (MS(-D)) in these specific attention functions., Methods: Six MS(+D) patients with attention deficits, six unimpaired MS(-D) patients, and age-, gender-, and education-matched healthy control subjects were examined with functional magnetic resonance imaging (fMRI). The experimental paradigm consisted of visual tasks requiring focused or divided attention., Results: Performance accuracy and reaction times were impaired in MS(+D) patients. This subgroup showed reduced activation within superior and inferior frontal gyrus during focused attention. Under conditions of divided attention decreased activity was found within middle and inferior frontal gyrus, inferior parietal structures, and occipital areas. No compensatory activity was observed. MS(-D) patients did neither differ in behavioral data nor in cortical activity in attention related structures from control subjects., Conclusions: The study found evidence for the neural correlate of attentional deficits in MS patients. In patients with specific attention deficits, reduced cortical activity in prefrontal and parietal areas, which are associated with attention and executive control, reflects the patients' reduced performance on a behavioral level. Our findings also suggest impaired top-down attentional control on sensory structures in these patients. In patients without verifiable attention deficits a normal functioning of structures relevant for executive attention was observed. Compensatory activity in these structures as a marker of reorganization in less pronounced stages of the disease was not found.

Electrophysiological studies found traumatic lesions of the prefrontal cortex (PFC) to affect the preparation of self-initiated movements. However, a precise localization of the observed effects has not been reported yet. Moreover, previous reports did not account for effects of lesion location. Therefore, the present study utilized functional MRI to investigate the influence of predominantly left or right hemispheric PFC lesions on movement preparation in chronic traumatic brain injury (TBI) patients. 18 TBI patients with MRI-defined contusions of the PFC as well as 18 healthy control subjects matched for age and gender were examined. Patients were divided into subgroups of predominantly left or right hemispheric lesions. During functional image acquisition, subjects performed self-initiated abductions of their right index finger. Neuropsychological tests of attention and working memory, which are supposed to modulate preparatory processes, were conducted. Patients with predominantly left contusions demonstrated enhanced activity of the dorsal lateral premotor cortex in comparison to healthy control subjects. In predominantly right lesioned patients, reduced activity within the right caudate head was observed. Compared to predominantly left lesioned patients, neuropsychological tests yielded reduced task performances in the right lesion subgroup. In line with previous electrophysiological research, imaging results of the present study are interpreted to represent altered preparatory networks in chronic prefrontal TBI patients. Since attentional and working memory functions are supposed to modulate preparatory processes, differences between the patient subgroups are suggested to result from the more pronounced cognitive impairments in the right-lesioned group.

Concepts of higher attention functions distinguish focused and divided attention. The present study investigated whether these mental abilities are mediated by common or distinct neural substrates. In a first experiment, 19 healthy subjects were examined with functional brain imaging (fMRI) while they attended to either one or both of two simultaneously presented visual information streams and responded to repetitive stimuli. This experiment resembled a typical examination of these mental functions with the single task demanding focused and the dual task conditions requiring divided attention. Both conditions activated a widespread, mainly right-sided network including dorso- and ventrolateral prefrontal structures, superior and inferior parietal cortex, and anterior cingulate gyrus. Under higher cognitive demands of divided attention, activity in these structures was enhanced and left-sided homologues were recruited. In a second experiment investigating another 17 subjects with almost the same paradigm, it was accounted for that in most dual task investigations of focused and divided attention the single tasks are easier to process than their combined presentation. Therefore, the task difficulty of focused attention tasks was increased. Almost the same activity pattern observed during division of attention was now found during focusing attention. Comparing both attentional states matched for task difficulty, differences were found in visual but not in prefrontal or parietal cortex areas. Our results suggest that focused and divided attention depend on largely overlapping neuronal substrates. Differences in activation patterns, especially in prefrontal and parietal areas, may result from unequal demands on executive control due to disparate processing requirements in typical tasks of focused and divided attention: Easier conditions begin with mainly right-sided activity within the attention network. As conditions become more difficult, left-lateralized homologue areas activate.

Activity of the prefrontal cortex (PFC) has been observed in previous block-design brain imaging studies of self-initiated movements. However, the meaning of these activations remained unclear. A functional MRI experiment was carried out, which utilized an epoch and an event-related analysis approach to the data. We hypothesized that event-related activity of the PFC would argue for a contribution to movement preparation. In contrast, epoch-, but not event-related activity pointed to tonic activations, probably reflecting enhanced attentional states or working memory processing. Twenty-one subjects were examined with 845 T2*-weighted images. During active phases, subjects were instructed to perform self-initiated movements of the right index finger with intertrial intervals of about 8 s. On single subject level, epoch- and event-related regressors were entered into a combined model, estimating the exclusive contribution of either regressor. For statistical inference on multisubject level, random effects analyses were performed. For the epoch regressor, activity within the right dorso- and ventrolateral prefrontal cortex, the bilateral insula, and the right inferior parietal lobe was observed. The event-related regressor detected activity within the right inferior parietal lobe, ventral from the activity found with the epoch regressor. The present results indicate a condition-, but not a movement-related function of the PFC in self-initiated movements. Furthermore, anatomically distinct regions within the inferior parietal cortex seem to be involved in condition-specific and movement-related processes. The observed condition-specific activations are suggested to reflect attentional or working memory processes, supervising task performance, rather than movement preparation or initiation.

Background and Purpose: The aim of the present study was to examine movement-related potentials (MRPs) in patients in the "chronic" stage after cortical stroke with recovered hemiparesis compared with healthy control subjects., Methods: Right index finger MRPs were derived from 12 patients > or =1 year after infarction in the territory of the left middle cerebral artery as well as from 12 control subjects. MRP components were compared between groups., Results: In the patient group, the component directly preceding movement onset (negative slope [NS]) was significantly reduced over the lesioned hemisphere contralateral to the movement. Furthermore, increased motor potentials (MPs) were observed over the contralesional hemisphere during movement execution. No changes in the early MRP (Bereitschaftspotential) reflecting movement preparation were found., Conclusions: Because the NS is supposed to be generated by the primary motor cortex, the decreased component over the lesioned hemisphere is interpreted to represent impaired contralateral M1 functioning in stroke patients. Contralesional activity has been reported as a probable sign of brain plasticity by functional imaging studies. Our results broaden these findings, giving new insights into the temporal course of movement-related brain activity in recovered cortical stroke patients. The data point to a functional reorganization of motor execution rather than preparation in poststroke hemiparesis.

Continuous image acquisition as used in most functional magnetic resonance imaging (fMRI) designs may conflict with specific experimental settings due to attendant, noisy gradient switching. In sparse fMRI, single images are recorded with a delay that allows the registration of the predicted peak of an evoked hemodynamic response (HDR). The aim of this study was to assess validity and sensitivity of single-trial sparse imaging within the visual domain. Thirteen subjects were scanned twice. Either continuous or sparse image acquisition was applied while participants viewed single trains of flashlights. Sparse fMRI results were compared to continuous event-related fMRI results on single- and multisubject level regarding spatial extent, overlap, and intensity of activation. In continuously recorded data, the variability of the HDR peak latency was examined because this measure determined the timing of sparse image acquisition. In sparse fMRI, the sensitivity was analyzed considering different numbers of averaged trials. Sparse imaging detected the core activity revealed using continuous fMRI. The intensity of signal changes detected by continuous or sparse fMRI was comparable. The HDR peak latency was stable across sessions, but intersubject and regional variability might have affected the power of sparse fMRI. In sparse imaging, adding trials resulted in extension of activation and improvement in statistical power. The comparison with established continuous fMRI confirms the validity of sparse imaging. Conventional event-related data acquisition and analysis provided more comprehensive results. However, only sparse fMRI offers the opportunity to apply stimuli and record further biosignals free of scanner-related artifacts during intervals without image acquisition.

Objective: The movement-related potential (MRP) is an EEG measure related to self-initiated movements, consisting of the Bereitschaftspotential (BP), the negative slope, and the motor potential. Since in a former study the BP was reduced in acute prefrontal traumatic brain injury (TBI) patients, the present study examined the MRPs' course in follow-up examinations., Methods: Right index finger MRPs of 22 patients with contusions of the prefrontal cortex were recorded 12, 26, and 52 weeks after TBI and compared to controls., Results: Within the patient group, a significant increase of the BP in the temporal course after TBI was observed. MRPs 12 and 26 weeks after TBI did not differ significantly from the control group. One year after TBI, significantly enhanced BPs were found., Conclusions: In the temporal course after prefrontal TBI, a recovery of the initially reduced BP was observed. The enhanced BP areas 1 year after TBI might represent the need for increased cognitive resources during movement preparation, supporting a recovered, but less effective neuronal network., Significance: The present study represents the first longitudinal follow-up study of MRPs after prefrontal brain lesion. The observed changes reflect the plastic capacity of the brain, reorganizing the neuronal network function.

In the present study, we used fMRI to investigate whether event-related preparatory processes of self-initiated and externally triggered movements differ. Twenty subjects were examined with 1000 T2*-weighted images in two consecutive sessions. During the first session subjects performed self-initiated abductions of the right index finger. For the second session subjects were instructed to perform the movements in response to visual cues. Number and timing of movements were matched between conditions. For statistical inference on multisubject level, random effects analyses were performed. Significantly enhanced activity during self-initiated compared to externally triggered movements was found within the left SMA, the left pre- and sensorimotor cortex, the right putamen, the left anterior cingulate gyrus, and the left inferior parietal lobe. The significantly increased activity during self-initiated in comparison to externally triggered movements might represent differential demands of the two conditions on the neuronal motor net during movement preparation, reflecting utilization of precise knowledge when to move in self-initiated movements. Our results emphasize a possible role of the primary motor cortex for movement preparation as observed in electrophysiological studies, but do not support a specific involvement of the dorsolateral prefrontal cortex as suggested by former block design studies.

Objective and Method: The present study utilised the PC-interactive pressure algesimetry to quantify cervical pain after whiplash injury. Pressure painfulness of the splenius and trapezius muscles was investigated in patients with an acute cervical syndrome after whiplash injury and compared to that of healthy subjects., Results: Pressure painfulness of neck and shoulder muscles was significantly increased in whiplash patients. The trapezius muscles were more painful left than right, probably due to the seat belt position., Conclusions: The computer-interactive pressure algesimetry enables a standardised, rater-independent quantification of cervical pain due to whiplash injury.

Objectives: An enhanced ipsilateral motor potential after prefrontal TBI is known. Our aim was to examine, whether this contributes to movement initiation or execution., Methods: EEGs of 22 patients and 28 healthy controls were recorded. Subjects performed self-initiated movements of their right index finger. From the resulting movement-related potentials difference curves of corresponding left and right hemispheric electrodes were calculated., Results: We observed significantly reduced difference curves at parietal electrodes P3 - P4 in the patient group during movement execution, but not at movement initiation., Conclusions: Our results point to compensatorily enhanced monitoring processes during movement execution following TBI. This is provided by enhanced activity of the ipsilateral postrolandic cortex, leading to the reduced preponderance observed in the present study.

Objective: Focal brain lesions due to traumatic brain injury (TBI) do not only lead to functional deficits in the lesion area, but also disturb the structurally intact neuronal network connected to the lesion site. Therefore we hypothesized dysfunctions of the cortical motor network after frontal TBI. The movement related potential (MRP) is an EEG component related to voluntary movement consisting of the Bereitschaftspotential (BP), the negative slope (NS), and the motor potential (MP). The aim of our study was to demonstrate alterations in the movement related cortical network in the acute stage after TBI by comparing our patients' MRPs to those of a healthy control group., Methods: EEGs of 22 patients with magnetic resonance imaging defined contusions of the prefrontal cortex were recorded within 8 weeks after TBI. We further recruited a healthy control group. The paradigm consisted of self-paced abductions of the right index finger., Results: Compared to healthy controls, the BP in the patient group was significantly reduced and its onset delayed. Moreover, an enhanced contribution of the postrolandic hemisphere ipsilateral to the movement and a reduced contribution of the left frontal cortex, ipsilateral to the lesion in the majority of the patients, were observed during motor execution (MP)., Conclusions: Anatomical connections between the prefrontal cortex and the supplementary motor area (SMA) are known to exist. We suggest that prefrontal lesions lead to reduced neuronal input into the SMA. This deficit in the preparatory motor network may cause the reduced BPs in our patients. Moreover, an increased need for attentional resources might explain the enhanced motor potentials during movement execution. In conclusion, we demonstrated altered MRPs in the acute stage after frontal TBI, which are a consequence of disturbed neuronal networks involved in the preparation and execution of voluntary movements.

Cortical reactions to rare task-related stimuli have been studied with electrophysiological methods in the assessment of the P300 component as well as in functional imaging studies with regard to oddball tasks. While functional magnetic resonance imaging studies using auditory stimuli have to deal with interference between auditory stimuli and scanner noise, the aim of our study was to assess auditory target processing with the sparse imaging method. Single volumes of echo-planar imaging were acquired 4 s following the onset of the stimuli of interest. In keeping with previous studies, target stimuli activated the insula, superior temporal gyrus, cingulate gyrus, middle frontal gyrus, parietal cortex and the cerebellum. Our results encourage the application of the sparse imaging method in experiments on cognitive processing elicited by auditory stimulation in a silent environment.

The conformational behaviour of host-guest peptides of the type Ac-Ala-Xxx-Ala-Ala-Xxx-Ala-Ala-Xxx-Ala-Ala-NH-PEGM (Xxx = alpha-aminoisobutyric acid (Aib), (S)-2-ethylalanine ((S)-Iva), (S)-2-methylserine ((S)-alpha-MeSer)) has been studied by CD spectroscopy in CF3CH2OH, CH3OH, and water and by i.r. spectroscopy in CHCl3 and in the solid state. In this way the relative helix-inducing potential of the two chiral alpha-methyl-alpha-amino acids (S)-Iva and (S)-alpha-MeSer could be established in comparison to the strong helix-former Aib. The results show that (S)-Iva exerts a comparable helix-inducing effect as Aib, making this amino acid a valuable complementary tool for the stabilization or induction of helices. No significant helix-promoting effect was observed for (S)-alpha-MeSer in polar solvents; however, the i.r.-spectroscopic data in CHCl3 and in the solid state point to a helical conformation under these conditions. Possible reasons for the different behaviour of (S)-Iva and (S)-alpha-MeSer are briefly discussed.