Task-dependent modulations of prefrontal and hippocampal activity during intrinsic word production

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on response restrictions but to a greater extent on associative binding processes, usually subserved by the hippocampus. To elucidate the relevance of the frontal and medial-temporal areas during verbal retrieval tasks, we applied varying degrees of response specification. During fMRI data acquisition, 18 subjects performed a free verbal association (FVA), a semantic verbal fluency (SVF) task, and a phonological verbal fluency (PVF) task. Externally guided word production served as a baseline condition to control for basic articulatory and reading processes. As expected, increased brain activity was observed in the left lateral and bilateral medial frontal cortices for SVF and PVF. The anterior cingulate gyrus was the only structure common to both fluency tasks in direct comparison to the less restricted FVA task. The hippocampus was engaged during associative and semantic retrieval. Interestingly, hippocampal activity was selectively evident during FVA in direct comparison to SVF when it was controlled for stimulus-response relations. The current data confirm the role of the left prefrontal-cingulate network in constrained word production. Hippocampal activity during spontaneous word production is a novel finding and seems to be dependent on the retrieval process (free vs. constrained) rather than the variety of stimulus-response relationships that is involved.     

Development and validation of the Rasch-based depression screening (DESC) using Rasch analysis and structural equation modelling

Questionnaires for the assessment of depression benefit from modern test construction like item-response-modelling. We developed two parallel 10 item depression questionnaires, the Rasch-based Depression Screening version 1 (DESC-I) and 2 (DESC-II), by combining Rasch analysis and structural equation modelling on patient samples suffering primarily from a mental disorder or from somatic diseases. Both scales base upon a Rasch homogeneous item bank and proved unidimensionality and good model fit. Cut-off scores with good sensitivity and specificity were developed using ROC analyses. Results suggest that DESC may be appropriately used to screen for depression and may be beneficial for repeated measurements.     

Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors

Cardiac-valve regurgitation observed in Parkinson patients treated with the ergoline dopamine receptor agonist 8beta-methylthiomethyl-6-propylergoline (pergolide) has been associated with the agonist efficacy of the drug at 5-hydroxytryptamine(2B) (5-HT(2B)) receptors. 5-HT(2A) receptors may also play a role in pergolide-induced cardiac-valve regurgitation. We studied the pharmacological profile of pergolide and eight derivatives in porcine vascular rings endowed with 5-HT(2B) and 5-HT(2A) receptors to detect the molecular fragment of the pergolide molecule that may be responsible for agonism at these receptors. Pergolide derivatives showed a different substitution pattern at N(6), and the side chain at C(8) was modified by replacement of the sulfur against an oxygen atom. We demonstrate that the potent agonism of pergolide both at 5-HT(2B) and 5-HT(2A) receptors is retained when the N(6) propyl substituent is replaced by ethyl. However, agonism can be converted into antagonism if N(6) propyl is replaced by methyl. The N(6)-unsubstituted derivative was a low efficacy 5-HT(2B) receptor partial agonist and a 5-HT(2A) receptor antagonist. This pharmacological pattern was also applicable for pergolide congeners with an oxygen in the side chain at C(8). 6-Methylpergolide retained agonist efficacy and potency compared with pergolide at human (h) D(2LONG(L)) and hD(2SHORT(S)) receptors as determined by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding. Based on the ability of pergolide to produce potent agonism at 5-HT(2B) receptors and the failure of 6-methylpergolide to act as an agonist but as a potent antagonist, we conclude that the N(6) propyl substituent of pergolide is crucial for 5-HT(2B) receptor agonism and thus a determinant of valvular regurgitation.     

Hippocampal dysfunction during free word association in male patients with schizophrenia

In schizophrenia, speech production deficits in patients with positive formal thought disorder (FTD e.g. loosening of associations and derailment) have been attributed to impairments in the semantic network. The brain area implicated in the retrieval of associated (i.e. relational) concepts is the hippocampus, a key region in the psychopathology of schizophrenia. However, its role in schizophrenic speech production and FTD in particular is yet little understood.

To investigate the neural correlates of associative verbal retrieval, twelve patients with schizophrenia with varying degrees of FTD and twelve matched healthy control subjects underwent a free verbal association (FVA), a semantic (SVF) and a phonological verbal fluency (PVF) task while brain activity was measured with fMRI. The tasks varied in the relational binding operations needed for linking the stimulus to the respective response.

Compared to control subjects, patients revealed attenuated left hippocampal activity during both semantic word generation tasks (FVA, SVF). Contrasting verbal fluency with FVA, a failure in recruiting the anterior cingulate gyrus emerged in the patient group. A negative correlation was found between right middle temporal activity and the severity of FTD during FVA.

The hippocampus seems to play a major role in word generation. In schizophrenia, attenuated hippocampal activity during semantic tasks strengthens the hypothesis of impaired relational memory processes, affecting thought and language.     

Radiophysical characteristics of different detectors for use in dosimetry

The present study investigated the radiophysical influences on the measurement of dosimetry basic data, attributable to field size, photon energy and detector type. A natural diamond detector, two ionisation chambers, different Si-diodes and a EBT-Gafchromic film were studied for this purpose. The characteristics of the detectors were investigated with regard to the measurement of output factors, lateral beam profiles and relative depth-dose curves for narrow and wide photon beams of 15 MV Significant differences in output factors were obtained with different detectors. For narrow fields, the natural diamond detector and the diodes PTW-60012 and SCX_WH-PFD measured output factors close to those of the EBT-Gafchromic film. The output facto rfor large fields was overestimated by the unshielded diode PTW 60012 and the PinPoint-chamber PTW-31006 because of their over-response to scattered photons. The relative depth dose distributions for wide beams at large depths agree well for the diamond, the ionisation chambers and the shielded Diode SCX_ WH-PFD and PTW-60008, while the measured dose was overestimated by an unshielded diode PTW-60012. Considering the influence due to the sensitive materials and the construction of the detectors the manufacturers of dosimeters have specified the application ranges for the various types of detectors.     

Regional Gas Exchange and Cellular Metabolic Activity in Ventilator-induced Lung Injury

Background: Alveolar overdistension and repetitive derecruitment-recruitment contribute to ventilator-induced lung injury (VILI). The authors investigated (1) whether inflammatory cell activation due to VILI was assessable by positron emission tomography and (2) whether cell activation due to dynamic overdistension alone was detectable when other manifestations of VILI were not yet evident.

Methods: The authors assessed cellular metabolic activity with [18F]fluorodeoxyglucose and regional gas exchange with [13N]nitrogen. In 12 sheep, the left ("test") lung was overdistended with end-inspiratory pressure of 50 cm H2O for 90 min, while end-expiratory derecruitment of this lung was either promoted with end-expiratory pressure of -10 cm H2O in 6 of these sheep (negative end-expiratory pressure [NEEP] group) or prevented with +10 cm H2O in the other 6 (positive end-expiratory pressure [PEEP] group) to isolate the effect of overdistension. The right ("control") lung was protected from VILI.

Results: Aeration decreased and shunt fraction increased in the test lung of the NEEP group. [18F]fluorodeoxyglucose uptake of this lung was higher than that of the control lung and of the test lung of the PEEP group, and correlated with neutrophil count. When normalized by tissue fraction to account for increased aeration of the test lung in the PEEP group, [18F]fluorodeoxyglucose uptake was elevated also in this group, despite the fact that gas exchange had not yet deteriorated after 90 min of overdistension alone.     

VERIDOS: A New Tool for Quality Assurance for Intensity Modulated Radiotherapy

Background: The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. Material and Methods: The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. Results: VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. Conclusions: VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology). Hintergrund: Der Einsatz intensitätsmodulierter Felder setzt ein erweitertes Qualitätssicherungskonzept voraus. Dies gliedert sich in einen rein maschinenbezogenen und einen fallbezogenen Teil. Als fallbezogen wird hier die Überprüfung eines individuellen Bestrahlungsplans, der am CT-Datensatz eines speziellen Patienten optimiert wurde und der für dessen Bestrahlung vorgesehen ist, verstanden. Dieser Teil der Qualitätssicherung nimmt in aller Regel viel Zeit in Anspruch, erbringt nur teilweise quantitative Ergebnisse und ist ohne zusätzliche Hilfsmittel wenig komfortabel. In den vorliegenden Ausführungen soll gezeigt werden, wie dieses Programm zur Optimierung des fallbezogenen Teils der Qualitätssicherung beiträgt. Material und Methode: Die Hauptfunktion des Programms besteht darin, im Bestrahlungsplanungsprogramm berechnete Dosisverteilungen mit im Phantom gemessenen Dosisverteilungen quantitativ zu vergleichen. Weitere Funktionen werden erläutert. Zur Erfassung der Dosisverteilung wurden zwei selbst entwickelte RW3-Phantome und sowohl GAFCHROMIC- als auch Kodak EDR2-Filme eingesetzt. Getestet wurde VERIDOS mit den Bestrahlungsplanungssystemen Helax-TMS und Brainscan. Ergebnisse: VERIDOS eignet sich zum Import von berechneten Dosismatrizen aus den Bestrahlungsplanungssystemen Helax-TMS und Brainscan. Es eignet sich zum Import von gemessenen und ausgelesenen Dosismatrizen aus der PTW-Dosimetriesoftware Mephysto. Der Import aus weiteren Bestrahlungsplanungssystemen und PC-Scannerapplikationen zur Filmdosimetrie ist generell möglich. In solch einem Fall müsste die Importfunktion an den jeweiligen Header der zu importierenden Matrix angepasst werden. Alle Funktionen des Auswerteprogramms wie Normierung (automatisch, manuell), Einfügen von Korrekturen (Schleierabzug, Faktoren), Überlagerung/Vergleich von Dosisverteilungen, Differenzbildung, Herausschneiden von überlagerten Profilen und Export funktionieren zuverlässig. Schlussfolgerungen: VERIDOS leistet einen Beitrag zur Optimierung der fallbezogenen Qualitätssicherung bei der intensitätsmodulierten Strahlentherapie (IMRT). Die verschiedenen Funktionen innerhalb des Programms bieten dem Klinikphysiker eine breite Basis zur Beurteilung der Güte der Realisierbarkeit des IMRT-Planes unabhängig davon, ob die Dosismodulation mit Kompensatoren oder MLC gewährleistet wird.     

Dosimetric Quality Assurance for Intensity–Modulated Radiotherapy Feasibility Study for a Filmless Approach

Purpose:  

Test and comparison of various 2–D real–time detectors for dosimetric quality assurance (QA) of intensity–modulated radiotherapy (IMRT) with the vision to replace radiographic films for 2–D dosimetry.     

Altered influence of polymorphonuclear leukocytes on coagulation in acute ischemic stroke

Polymorphonuclear (PMN) and mononuclear (MN) leukocytes possess procoagulant and anticoagulant activity which could be involved in both formation and dissolution of thrombi. We investigated if coagulant properties of circulating leukocytes are altered in patients within three days after acute ischemic stroke (n=22) as compared to a control group (n=22) matched for sex and age. The recalcification time with autologous plasma did not differ between patients and control subjects. Circulating PMNs were procoagulant in all subjects, however, they were less procoagulant in patients (−18.1 [−13.4 − −22.8] % of control experiments; mean [95% confidence interval]) than in controls subjects (−31.9 [−27.4 − −36.4] %; P=0.0002). In contrast, MNs were similarly procoagulant in both groups. In the activated partial thromboplastin time (aPTT), there was a non-significant trend to less procoagulant PMNs in patients (−6.7 [−5.1 − −8.2] %) than in control subjects (−8.4 [−6.4 − −10.5] %). The recalcification time with pooled human plasma showed similar results as with autologous plasma. The procoagulant activity of PMNs increased in follow-up measurements in patients. Upon stimulation with FMLP, the procoagulant activity of PMNs decreased in control subjects but did not change significantly in patients. In the acute stage after ischemic stroke, circulating PMNs exhibit a decreased capability to stimulate coagulation, a feature which reflects cell activation and which may be a reaction on thrombus formation and ischemic tissue damage.