Response selection deficits in melancholic but not nonmelancholic unipolar major depression

One consistent functional imaging finding from patients with major depression has been abnormality of the anterior cingulate cortex (ACC). Hypoperfusion has been most commonly reported, but some studies suggest relative hyperperfusion is associated with response to somatic treatments. Despite these indications of the possible importance of the ACC in depression there have been relatively few cognitive studies ACC function in patients with major depression. The present study employed a series of reaction time (RT) tasks involving selection with melancholic and nonmelancholic depressed patients, as well as age-matched controls. Fifteen patients with unipolar major depression (7 melancholic, 8 nonmelancholic) and 8 healthy age-matched controls performed a series of response selection tasks (choice RT, spatial Stroop, spatial stimulus-response compatibility (SRC), and a combined Stroop + SRC condition). Reaction time and error data were collected. Melancholic patients were significantly slower than controls on all tasks but were slower than nonmelancholic patients only on the Stroop and Stroop + SRC conditions. Nonmelancholic patients did not differ from the control group on any task. The Stroop task seems crucial in differentiating the two depressive groups, they did not differ on the choice RT or SRC tasks. This may reflect differential task demands, the SRC involved symbolic manipulation that might engage the dorsal ACC and dorsolateral prefrontal cortex (DLPFC) to a greater extent than the, primarily inhibitory, Stroop task which may engage the ventral ACC and orbitofrontal cortex (OFC). This might suggest the melancholic group showed a greater ventral ACC-OFC deficit than the nonmelancholic group, while both groups showed similar dorsal ACC-DLPFC deficit.

Stimulus-response curve of human motor nerves: multicenter assessment of various indexes.

The value of various indexes to characterize the stimulus-response curve of human motor nerves was assessed in 40 healthy subjects recruited from four European centers of investigation (Créteil, Lausanne, Liège, Marseille). Stimulus-response curves were established by stimulating the right median and ulnar motor nerves at the wrist, with stimulus durations of 0.05 and 0.5 ms. The following parameters were studied: the threshold intensity of stimulation to obtain 10% (I 10), 50% (I 50), and 90% (I 90) of the maximal compound muscle action potential, the ratios I 10/I 50, I 90/I 50, (I 90 - I 10)/I 10, (I 90-I 50)/I 50, and (I 50 - I 10)/I 10, and the slopes of the stimulus-response curves with or without normalization to I 50. For each parameter, within-center variability and reproducibility (in a test-retest study) were assessed and between-center comparisons were made. For most of the parameters, the results varied significantly within and between the centers. Within the centers, only the ratios I 10/I 50 and I 90/I 50 were found constant and reproducible. Between the centers, the absolute intensity thresholds (I 10, I 50, I 90) and the ratio I 90/I 50 did not show significant differences at stimulus duration of 0.5 ms, whatever the stimulated nerve. The reduced variability and good reproducibility of the ratios I 10/I 50 and I 90/I 50 open perspectives in neurophysiological practice for the use of these indexes of the stimulus-response curve, a rapid and noninvasive test.

Statistical modeling of large microarray data sets to identify stimulus-response profiles

A statistical modeling approach is proposed for use in searching large microarray data sets for genes that have a transcriptional response to a stimulus. The approach is unrestricted with respect to the timing, magnitude or duration of the response, or the overall abundance of the transcript. The statistical model makes an accommodation for systematic heterogeneity in expression levels. Corresponding data analyses provide gene-specific information, and the approach provides a means for evaluating the statistical significance of such information. To illustrate this strategy we have derived a model to depict the profile expected for a periodically transcribed gene and used it to look for budding yeast transcripts that adhere to this profile. Using objective criteria, this method identifies 81% of the known periodic transcripts and 1,088 genes, which show significant periodicity in at least one of the three data sets analyzed. However, only one-quarter of these genes show significant oscillations in at least two data sets and can be classified as periodic with high confidence. The method provides estimates of the mean activation and deactivation times, induced and basal expression levels, and statistical measures of the precision of these estimates for each periodic transcript.

The stimulus-response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis

The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve showed a gradual increase in CMAP size with increasing stimulus intensity, although one or two discrete steps were sometimes observed in the upper half of the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 mu Vms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.

Électrophysiologie cognitive et motrice du syndrome Gilles de la Tourette

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Effets électrophysiologiques d’une thérapie cognitivo-comportementale pour traiter le syndrome de Gilles de la Tourette et le trouble de tics chroniques

Les troubles des tics, comme le syndrome de Gilles de la Tourette et le trouble de tics chroniques, sont des conditions neuropsychiatriques impliquant des tics moteurs et/ou phoniques. En plus de nombreuses comorbidités, les patients qui en sont atteints ont aussi des difficultés neuropsychologiques, notamment au niveau de l’inhibition et des fonctions motrices. La thérapie cognitivo-comportementale permet d’améliorer les tics et la condition générale de ces patients. Nous avons donc enregistré, durant une tâche de compatibilité stimulus-réponse, les potentiels évoqués cognitifs et les potentiels de latéralisation motrice (lateralized readiness potential; LRP) chez 20 patients atteints de trouble des tic avant et après une thérapie cognitivo-comportementale, et chez 20 participants contrôles. Chez les patients atteints de trouble des tics, nos résultats ont révélé une apparition plus tardive de l’amorce du LRP moyenné par rapport au stimulus, une amplitude plus élevée du LRP moyenné par rapport à la réponse, et une suractivation frontale liée aux processus d’inhibition. Suite à la thérapie, le retard au niveau de la latence de l’amorce du LRP moyenné par rapport à la réponse est comblé et l’amplitude du LRP moyenné par rapport à la réponse est normalisée, mais pas la suractivation frontale liée à l’inhibition. Cela suggère donc que la thérapie induit une modification des processus prémoteurs de sélection et de préparation de la réponse, ainsi que des processus d’exécution motrice, mais n’altère pas la suractivation frontale reliée aux fonctions inhibitrices. Étant donnés ces résultats, nous suggérons que la thérapie cognitivo-comportementale induit une modification du fonctionnement des aires motrices du cerveau.

The Role of Epistemic Monitoring in Language Comprehension

In der psycholinguistischen Forschung ist die Annahme weitverbreitet, dass die Bewertung von Informationen hinsichtlich ihres Wahrheitsgehaltes oder ihrer Plausibilität (epistemische Validierung; Richter, Schroeder & Wöhrmann, 2009) ein strategischer, optionaler und dem Verstehen nachgeschalteter Prozess ist (z.B. Gilbert, 1991; Gilbert, Krull & Malone, 1990; Gilbert, Tafarodi & Malone, 1993; Herbert & Kübler, 2011). Eine zunehmende Anzahl an Studien stellt dieses Zwei-Stufen-Modell von Verstehen und Validieren jedoch direkt oder indirekt in Frage. Insbesondere Befunde zu Stroop-artigen Stimulus-Antwort-Kompatibilitätseffekten, die auftreten, wenn positive und negative Antworten orthogonal zum aufgaben-irrelevanten Wahrheitsgehalt von Sätzen abgegeben werden müssen (z.B. eine positive Antwort nach dem Lesen eines falschen Satzes oder eine negative Antwort nach dem Lesen eines wahren Satzes; epistemischer Stroop-Effekt, Richter et al., 2009), sprechen dafür, dass Leser/innen schon beim Verstehen eine nicht-strategische Überprüfung der Validität von Informationen vornehmen. Ausgehend von diesen Befunden war das Ziel dieser Dissertation eine weiterführende Überprüfung der Annahme, dass Verstehen einen nicht-strategischen, routinisierten, wissensbasierten Validierungsprozesses (epistemisches Monitoring; Richter et al., 2009) beinhaltet. Zu diesem Zweck wurden drei empirische Studien mit unterschiedlichen Schwerpunkten durchgeführt. Studie 1 diente der Untersuchung der Fragestellung, ob sich Belege für epistemisches Monitoring auch bei Informationen finden lassen, die nicht eindeutig wahr oder falsch, sondern lediglich mehr oder weniger plausibel sind. Mithilfe des epistemischen Stroop-Paradigmas von Richter et al. (2009) konnte ein Kompatibilitätseffekt von aufgaben-irrelevanter Plausibilität auf die Latenzen positiver und negativer Antworten in zwei unterschiedlichen experimentellen Aufgaben nachgewiesen werden, welcher dafür spricht, dass epistemisches Monitoring auch graduelle Unterschiede in der Übereinstimmung von Informationen mit dem Weltwissen berücksichtigt. Darüber hinaus belegen die Ergebnisse, dass der epistemische Stroop-Effekt tatsächlich auf Plausibilität und nicht etwa auf der unterschiedlichen Vorhersagbarkeit von plausiblen und unplausiblen Informationen beruht. Das Ziel von Studie 2 war die Prüfung der Hypothese, dass epistemisches Monitoring keinen evaluativen Mindset erfordert. Im Gegensatz zu den Befunden anderer Autoren (Wiswede, Koranyi, Müller, Langner, & Rothermund, 2013) zeigte sich in dieser Studie ein Kompatibilitätseffekt des aufgaben-irrelevanten Wahrheitsgehaltes auf die Antwortlatenzen in einer vollständig nicht-evaluativen Aufgabe. Die Ergebnisse legen nahe, dass epistemisches Monitoring nicht von einem evaluativen Mindset, möglicherweise aber von der Tiefe der Verarbeitung abhängig ist. Studie 3 beleuchtete das Verhältnis von Verstehen und Validieren anhand einer Untersuchung der Online-Effekte von Plausibilität und Vorhersagbarkeit auf Augenbewegungen beim Lesen kurzer Texte. Zusätzlich wurde die potentielle Modulierung dieser Effeke durch epistemische Marker, die die Sicherheit von Informationen anzeigen (z.B. sicherlich oder vielleicht), untersucht. Entsprechend der Annahme eines schnellen und nicht-strategischen epistemischen Monitoring-Prozesses zeigten sich interaktive Effekte von Plausibilität und dem Vorhandensein epistemischer Marker auf Indikatoren früher Verstehensprozesse. Dies spricht dafür, dass die kommunizierte Sicherheit von Informationen durch den Monitoring-Prozess berücksichtigt wird. Insgesamt sprechen die Befunde gegen eine Konzeptualisierung von Verstehen und Validieren als nicht-überlappenden Stufen der Informationsverarbeitung. Vielmehr scheint eine Bewertung des Wahrheitsgehalts oder der Plausibilität basierend auf dem Weltwissen – zumindest in gewissem Ausmaß – eine obligatorische und nicht-strategische Komponente des Sprachverstehens zu sein. Die Bedeutung der Befunde für aktuelle Modelle des Sprachverstehens und Empfehlungen für die weiterführende Forschung zum Vehältnis von Verstehen und Validieren werden aufgezeigt.

Facilitatory effects of an auditory warning stimulus in a visual location identification task and a visual shape identification task

The occurrence of a weak auditory warning stimulus increases the speed of the response to a subsequent visual target stimulus that must be identified. This facilitatory effect has been attributed to the temporal expectancy automatically induced by the warning stimulus. It has not been determined whether this results from a modulation of the stimulus identification process, the response selection process or both. The present study examined these possibilities. A group of 12 young adults performed a reaction time location identification task and another group of 12 young adults performed a reaction time shape identification task. A visual target stimulus was presented 1850 to 2350 ms plus a fixed interval (50, 100, 200, 400, 800, or 1600 ms, depending on the block) after the appearance of a fixation point, on its left or right side, above or below a virtual horizontal line passing through it. In half of the trials, a weak auditory warning stimulus (S1) appeared 50, 100, 200, 400, 800, or 1600 ms (according to the block) before the target stimulus (S2). Twelve trials were run for each condition. The S1 produced a facilitatory effect for the 200, 400, 800, and 1600 ms stimulus onset asynchronies (SOA) in the case of the side stimulus-response (S-R) corresponding condition, and for the 100 and 400 ms SOA in the case of the side S-R non-corresponding condition. Since these two conditions differ mainly by their response selection requirements, it is reasonable to conclude that automatic temporal expectancy influences the response selection process.

Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets

Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca2 2+ signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca2 2+signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally,weexplored the status of Ca2 2+-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase Cα as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the β-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity. Copyright © 2010 by The Endocrine Society.

NMDA receptors in the lateral hypothalamus have an inhibitory influence on the tachycardiac response to acute restraint stress in rats

The aim of the present study was to investigate the role of the lateral hypothalamus (LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor CoCl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate (HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl-d-aspartate (NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of CoCl2. No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non-NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress. The bilateral microinjection of the CoCl2 or LY235959 into the LH enhanced the HR increase evoked by restraint stress without affecting the blood pressure increase. Intravenous administration of the homatropine methyl bromide abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. These results suggest that such LH influence is mediated by local NMDA glutamate receptors and involves parasympathetic nervous activation. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Facilitatory effects of an auditory warning stimulus in a visual location identification task and a visual shape identification task

The occurrence of a weak auditory warning stimulus increases the speed of the response to a subsequent visual target stimulus that must be identified. This facilitatory effect has been attributed to the temporal expectancy automatically induced by the warning stimulus. It has not been determined whether this results from a modulation of the stimulus identification process, the response selection process or both. The present study examined these possibilities. A group of 12 young adults performed a reaction time location identification task and another group of 12 young adults performed a reaction time shape identification task. A visual target stimulus was presented 1850 to 2350 ms plus a fixed interval (50, 100, 200, 400, 800, or 1600 ms, depending on the block) after the appearance of a fixation point, on its left or right side, above or below a virtual horizontal line passing through it. In half of the trials, a weak auditory warning stimulus (S1) appeared 50, 100, 200, 400, 800, or 1600 ms (according to the block) before the target stimulus (S2). Twelve trials were run for each condition. The S1 produced a facilitatory effect for the 200, 400, 800, and 1600 ms stimulus onset asynchronies (SOA) in the case of the side stimulus-response (S-R) corresponding condition, and for the 100 and 400 ms SOA in the case of the side S-R non-corresponding condition. Since these two conditions differ mainly by their response selection requirements, it is reasonable to conclude that automatic temporal expectancy influences the response selection process.