Gerontopsychosomatik

Ohne Zusammenfassung     

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood.

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.     

Left inferior parietal cortex integrates time and space during collision judgments

Left inferior parietal lobe lesions can cause perturbation of the space-time plans underlying skilled actions. But does the perceptual integration of spatiotemporal information use the same neural substrate or is the role of the left inferior parietal cortex restricted to visuomotor transformations? We use fMRI and a collision judgment paradigm to examine whether the left inferior parietal cortex integrates temporal and spatial variables in situations in which no complex action and no visuomotor transformation is required. We used a perceptual task in which healthy subjects indicated by simple button presses whether two moving objects (of the same or different size) would or would not collide with each other. This task of interest was contrasted with a control task that employed the same stimuli and identical motor responses but in which the size of the two moving objects had to be compared. To assess putative differential eye-movement effects both tasks were performed with and without central fixation. Analysis of the fMRI data (employing a random-effects model and SPM99) showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus) only. These results show that left inferior parietal cortex is involved in the integration of perceptual spatiotemporal information and thus provide a neural correlate for the use of space-time plans (whose perturbation can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the data suggest that the left supramarginal gyrus combines temporal and spatial variables more widely than previously supposed.     

Primary ICD-therapy in patients with advanced heart failure: selection strategies and future trials

Background  For allocation of primary ICD-therapy, a possible lower limit of inclusion criteria—defining overly advanced heart failure—is less well investigated. Also, a multi-variable approach to stratification beyond ejection fraction (LVEF) appears warranted. We examined whether adding a selection limit of peak VO₂ ≤ 14 ml/kg/min to LVEF ≤ 20% improves stratification. Furthermore, we sought to provide current survival data and a size-estimate for prospective trials based on real-life data for this high risk cohort. Methods  In our prospective clinical registry 1,926 patients with systolic CHF were recruited consecutively since 1994. Of these patients, 292 met the selection criteria described above. The mean age was 57.6 ± 9.5 years, 83% were male, 37% had ischemic cardiomyopathy and 28% received primary ICD-therapy. All cause mortality was considered as end point. Results  Median follow-up was 45 (18–86) months. ICD was not a significant predictor of outcome either for the entire population, or grouped according to aetiology of CHF. Still, 3-year mortality was 15% (ICD-patients) Vs. 28% (non-ICD-patients); P = 0.05; under combination medical therapy. Inversely, in ICD-patients medical combination therapy conveyed a significant survival benefit (P < 0.001). Consequently, the number-needed-to-treat was eight under combination therapy and the size estimate amounts to 300 patients for a prospective trial in this cohort. Conclusion  A cut-off of LVEF ≤ 20% and pVO₂ ≤ 14 ml/kg/min could identify patients that do not draw a significant survival benefit from adjunct primary ICD-therapy. Our results indicate the need for a specific randomized trial in this cohort. The according mortality data and a size estimate are provided.     

The right temporoparietal junction in attention and social interaction: A transcranial magnetic stimulation study

The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta‐analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796–807, 2016. © 2015 Wiley Periodicals, Inc .     

Causality between local field potentials of the subthalamic nucleus and electromyograms of forearm muscles in Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, although its precise mechanisms remain poorly understood. To gain further insight into the mechanisms underlying deep brain stimulation, we analysed the causal relationship between forearm muscle activity and local field potentials derived from the subthalamic nucleus. In 19 patients suffering from Parkinson’s disease of the akinetic‐rigid subtype, we calculated the squared partial directed coherence between muscles of the contralateral forearm and the subthalamic nucleus or zona incerta during both a rest and a hold condition of the arm. For both recording regions, data analysis revealed that, during the rest condition, electromyographic activity was significantly more often ‘Granger‐causal’ for the local field potentials than the opposite causation. In contrast, during the hold condition, no significant difference was found in the occurrence of causalities. Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, we found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences’, suggesting that its role is more complex than a simple driving nucleus in the basal ganglia loop. Therefore, the effect of deep brain stimulation in the subthalamic nucleus could, at least in part, result from a blockade of pathological afferent input.     

Long-term effects of methylphenidate on neural networks associated with executive attention in children with ADHD: results from a longitudinal functional MRI study

ObjectiveLittle is known about the long-term effects of stimulants on the functional organization of the developing brain. Nonacute effects of stimulants on neural activity related to three aspects of attention (alerting, reorienting, and executive control) were examined in children with attention-deficit/hyperactivity disorder (ADHD) using a longitudinal functional magnetic resonance imaging approach.MethodNine boys with ADHD were scanned while drug naïve (t1) and after 1 year of methylphenidate treatment (t2). Eleven matched controls were also investigated twice. ADHD children stopped medication 1 week before t2.ResultsAlthough all of the children showed stable alerting and reorienting performance from t1 to t2, normal controls significantly improved their executive control performance at t2, whereas children with ADHD did not. Neurally, controls showed a larger increase in neural activity from t1 to t2 in regions critical to task performance (i.e., in the temporoparietal junction during reorienting of attention and in the anterior cingulate cortex during executive control) compared to the patient group. However, only children with ADHD showed a decrease in neural activity in the insula and putamen during reorienting, indicating a reduction in compensatory brain activation over time.ConclusionsThese data suggest that 1 year of MPH treatment may be beneficial, albeit insufficient, to show enduring normalization of neural correlates of attention.     

Functional interactions during the retrieval of conceptual action knowledge: an fMRI study

Impaired retrieval of conceptual knowledge for actions has been associated with lesions of left premotor, left parietal, and left middle temporal areas [Tranel, D., Kemmerer, D., Adolphs, R., Damasio, H., & Damasio, A. R. Neural correlates of conceptual knowledge for actions. Cognitive Neuropsychology, 409-432, 2003]. Here we aimed at characterizing the differential contribution of these areas to the retrieval of conceptual knowledge about actions. During functional magnetic resonance imaging (fMRI), different categories of pictograms (whole-body actions, manipulable and nonmanipulable objects) were presented to healthy subjects. fMRI data were analyzed using SPM2. A conjunction analysis of the neural activations elicited by all pictograms revealed ( p<.05, corrected) a bilateral inferior occipito-temporal neural network with strong activations in the right and left fusiform gyri. Action pictograms contrasted to object pictograms showed differential activation of area MT+, the inferior and superior parietal cortex, and the premotor cortex bilaterally. An analysis of psychophysiological interactions identified contribution-dependent changes in the neural responses when pictograms triggered the retrieval of conceptual action knowledge: Processing of action pictograms specifically enhanced the neural interaction between the right and left fusiform gyri, the right and left middle temporal cortices (MT+), and the left superior and inferior parietal cortex. These results complement and extend previous neuropsychological and neuroimaging studies by showing that knowledge about action concepts results from an increased coupling between areas concerned with semantic processing (fusiform gyrus), movement perception (MT+), and temporospatial movement control (left parietal cortex).     

What is "odd" in Posner's location-cueing paradigm? Neural responses to unexpected location and feature changes compared

Within the parietal cortex, the temporo-parietal junction (TPJ) and the intraparietal sulcus (IPS) seem to be involved in both spatial and nonspatial functions: Both areas are activated when misleading information is provided by invalid spatial cues in Posner's location-cueing paradigm, but also when infrequent deviant stimuli are presented within a series of standard events. In the present study, we used functional magnetic resonance imaging to investigate the distinct and shared brain responses to (i) invalidly cued targets requiring attentional reorienting, and (ii) to target stimuli deviating in color and orientation leading to an oddball-like distraction effect. Both unexpected location and feature changes were accompanied by a significant slowing of manual reaction times. Bilateral TPJ and right superior parietal lobe (SPL) activation was observed in response to invalidly as compared to validly cued targets. In contrast, the bilateral inferior occipito-temporal cortex, the left inferior parietal cortex, right frontal areas, and the cerebellum showed stronger activation in response to deviant than to standard targets. Common activations were observed in the right angular gyrus along the IPS and in the right inferior frontal gyrus. We conclude that the superior parietal and temporo-parietal activations observed here as well as previously in location-cueing paradigms do not merely reflect the detection and processing of unexpected stimuli. Furthermore, our data suggest that the right IPS and the inferior frontal gyrus are involved in attentional selection and distractor processing of both spatial and nonspatial features.     

Action verbs and the primary motor cortex: a comparative TMS study of silent reading, frequency judgments, and motor imagery

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS(M1) vs. TMS(vertex)) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation within the same experiment: subjects indicated with their left foot when they (i) had finished reading, (ii) had judged whether the corresponding movement involved a hand rotation after simulating the hand movement, and (iii) had judged whether they would frequently encounter the action verb in a newspaper (TASK: silent reading, motor imagery, and frequency judgment). Response times were compared between TMS(M1) and TMS(vertex), both applied at different time points after stimulus onset (DELAY: 150, 300, 450, 600, and 750 ms). TMS(M1) differentially modulated task performance: there was a significant facilitatory effect of TMS(M1) for the imagery task only (about 88 ms), with subjects responding about 10% faster (compared to TMS(vertex)). In contrast, response times for silent reading and frequency judgments were unaffected by TMS(M1). No differential effect of the time point of TMS(M1) was observed. The differential effect of TMS(M1) when subjects performed a motor imagery task (relative to performing silent reading or frequency judgments with the same set of verbs) suggests that the primary motor cortex is critically involved in processing action verbs only when subjects are simulating the corresponding movement. This task-dependent effect of hand motor cortex TMS on the processing of hand-related action verbs is discussed with respect to the notion of embodied cognition and the associationist theory.