Tilman Hensch

Dopamine and cognitive control: the prospect of monetary gains influences the balance between flexibility and stability in a set-shifting paradigm

Positive affect and the activity of the neurotransmitter dopamine seem to shift the balance between cognitive flexibility vs stability towards increased flexibility. Here we examined the impact of prospective monetary gains on this balance. Seventy healthy volunteers performed a set‐shifting task comprising a condition in which a bias towards new stimuli helped to overcome perseveration and increased flexibility, and a second condition in which directing attention towards new stimuli increased distractibility. From previous studies of executive functions, two contrasting predictions can be derived: the prospect of monetary gains might either increase cognitive flexibility due to a dopamine release in the prefrontal cortex or increase stability due to an assessment of high utility of action processed in the anterior cingulated cortex and orbitofrontal cortex. Overall, we observed increased cognitive stability in the face of prospective gains (η2 = 7%). However, this effect was modulated by the subjective evaluation of the reward cues: participants who reported increasing their effort in response to reward cues showed increased cognitive stability, whereas those who reported a positive and relaxed attitude towards the reward cues showed increased flexibility (η2 = 11%). The results thus suggest that the flexibility–stability balance is modulated by the perceived effort needed to receive the potential reward. On a neuropsychological level, an interaction of dopaminergic and noradrenergic processes might be involved in the allocation of control.

Serotonin transporter gene variation and stressful life events impact processing of fear and anxiety

Genetic variation of the serotonin transporter (5-HTT) has been associated with fear- and anxiety-related behaviours. The amygdala is considered crucial in emotional modulation and stronger amygdala reactivity in response to fearful stimuli has been found in carriers of the short (S) allele of the 5-HTT gene in imaging studies. Additionally, reactivity of amygdala-innervated effectory systems is also of particular interest. We recently reported the impact of a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) on the acoustic startle reflex. Here, we attempted to replicate and extend these findings. Startle magnitudes to intense noise bursts as measured with the eyeblink response were recorded in 106 healthy volunteers during baseline without additional stimulation and while they viewed pictures of three valence conditions: unpleasant, pleasant and neutral. Subjects were genotyped for the tri-allelic functional polymorphism 5-HTTLPR. In replication of our previous findings we found that carriers of the low-expressing S or LG alleles exhibited stronger overall startle responses across conditions than LA/LA homozygotes, while there were no differences in emotional startle modulation between the two genetic groups. In addition, we found that the recent experience of stressful life events resulted in overall higher startle responses and less startle habituation across blocks. The results replicate and emphasize the role of 5-HTTLPR and stress on the overall startle response as a possible genetically driven endophenotype for anxiety-related behaviour.

Further Evidence for an Association of 5-HTTLPR with Intensity Dependence of Auditory-Evoked Potentials

Intensity dependence of auditory-evoked potentials (IAEP) has been suggested as an indicator of central serotonergic neurotransmission. Two recent studies investigated a possible association of IAEP with a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) that has a short (s) and a long (l) variant. Although both studies found an association between 5-HTTLPR and IAEP, Gallinat et al found l/l individuals to exhibit lower IAEP, whereas Strobel et al observed stronger IAEP in l/l individuals. These conflicting results require further evaluation and more attention needs to be paid to variables that are known to be confounded with the effects of IAEP and 5-HTTLPR. Using a paradigm comparable to Strobel et al, the present study analyzes the effect of 5-HTTLPR on IAEP in a healthy male student sample (N=91; age=23 years, SD=1.9) that was homogenous for most significant confounding variables. A stronger IAEP was shown in l/l individuals, irrespective of the method of IAEP parametrization. This also held at retest after 3 weeks in a subsample (N=18). Given the successful replication of Strobel et al, several possible reasons for conflicting results with regard to Gallinat et al are discussed. It is argued that the most significant difference between Gallinat et al on the one hand, and Strobel et al and this study on the other, is that different intensity ranges are used which impact IAEP. Therefore, this study encourages further analysis of dose dependence of results.

Assessment of Wakefulness and Brain Arousal Regulation in Psychiatric Research

During the last few decades, much knowledge has been gained about sleep being a heterogeneous condition with several distinct sleep stages that represent fundamentally different physiological states. The same applies for the wake state which also comprises distinct global functional states (called vigilance stages). However, various terms and concepts have been introduced describing different aspects of wakefulness, and accordingly several methods of assessment exist, e.g. sleep laboratory assessments (Multiple Sleep Latency Test, Maintenance of Wakefulness Test), questionnaires (Epworth Sleepiness Scale, Karolinska Sleepiness Scale), behavioural tasks (Psychomotor Vigilance Test) or electroencephalography (EEG)-based assessments (Alpha Attenuation Test, Karolinska Drowsiness Test). Furthermore, several theoretical concepts about the regulation of sleep and wakefulness have been put forward, and physiological correlates have been identified. Most relevant for healthy functioning is the regulation of brain arousal and the adaption of wakefulness to the environmental and situational needs so that the optimal balance between energy conservation and responsiveness can be obtained. Since one approach to the assessment of brain arousal regulation is the classification of EEG vigilance stages, a computer-based algorithm (Vigilance Algorithm Leipzig) has been introduced, allowing classification of EEG vigilance stages in EEG recordings under resting conditions. The time course of EEG vigilance stages in EEGs of 15-20 min duration allows estimation of the individual arousal regulation (hyperstable, adaptive, or unstable vigilance pattern). The vigilance model of affective disorders and attention-deficit/hyperactivity disorder links a disturbed arousal regulation to the pathogenesis of psychiatric disorders and accordingly helps to explain and possibly also predict treatment effects of pharmacological and non-pharmacological interventions for these conditions.

Electrophysiological and behavioral correlates of polymorphisms in the transcription factor AP-2β coding gene

Transcription factor AP-2beta may influence brain monoaminergic systems by regulating target genes. Several monoaminergic genes, including the serotonin transporter gene, have AP-2beta binding sites. Late auditory-evoked potentials (P1, N1/P2) and impulsiveness-related personality traits are correlated, and both are modulated by monoaminergic neurotransmission. The present study assesses the impact of two AP-2beta polymorphisms (VNTRs within intron 1 and 2) together with the serotonin transporter polymorphism 5-HTTLPR on late auditory-evoked potentials and personality for the first time. EEG was recorded from 91 male subjects at central electrode positions while tones of six intensity levels were presented. Additionally, subjects completed personality questionnaires. Both AP-2beta polymorphisms revealed significant main effects on P1, and haplotype analysis confirmed the contribution of both AP-2beta-polymorphisms. Additionally, AP-2beta and 5-HTTLPR showed interactions with respect to P1. 5-HTTLPR revealed a main effect on N1/P2 but not P1. Impulsiveness showed an association with intron 1 VNTR. The results are discussed with respect to differential impact of AP-2beta polymorphisms and 5-HTTLPR on the monoaminergic systems. The findings promote replication in a larger sample and suggest a potential usefulness of AP-2beta polymorphisms in explaining or predicting central nervous diseases, drug effects and side effects.

Elektroenzephalographie in der Psychopharmakotherapie

Die Elektroenzephalographie (EEG) ermoglicht es, die Fluktuationen der kortikalen hirnelektrischen Aktivitat (»Melodie der Hirnrinde«) zeitgetreu abzubilden. Nachdem erste EEG-Ableitungen in den Jahren 1924–1929 von dem Psychiater Hans Berger durchgefuhrt worden waren (Berger 1929), erlangte dieses Verfahren einen wichtigen Stellenwert in der Diagnostik und Verlaufsbeobachtung neuropsychiatrischer Erkrankungen und war lange Zeit das wichtigste technische Untersuchungsverfahren, um die klinische Diagnostik zu erganzen. Mit den neuen Moglichkeiten der strukturellen Bildgebung wurde das EEG fur Fragen der Hirnstrukturdiagnostik entbehrlich. Auch mit neuen Verfahren der Hirnfunktionsdiagnostik wie z. B. der funktionellen Magentresonanztomographie (fMRT), Positronenemissionstomographie (PET) oder Single-Photon-Emissionstomographie (SPECT) erwuchs dem EEG Konkurrenz.

ACROSS-SESSION REPRODUCIBILITY OF AUTOMATIC WHITE MATTER HYPERINTENSITIES SEGMENTATION: A EUROPEAN MULTI-SITE 3T STUDY

Federica Ribaldi, Moira Marizzoni, Jorge Jovicich, Clarissa Ferrari, Beatriz Bosch, David Bartr es-Faz, Bernhard W. M€uller, Jens Wiltfang, Ute Fiedler, Luca Roccatagliata, Agnese Picco, Flavio Nobili, Olivier Blin, Stephanie Bombois, Renaud Lopes, Regis Bordet, Julien Sein, Jean-Philippe Ranjeva, Mira Didic, Helene GrosDagnac, Pierre Payoux, Giada Zoccatelli, Franco Alessandrini, Alberto Beltramello, N uria Bargallo, Antonio Ferretti, Massimo Caulo, Marco Aiello, Carlo Cavaliere, Andrea Soricelli, Lucilla Parnetti, Robertto Tarducci, Piero Floridi, Magda Tsolaki, Manos Constantinides, Antonios Drevelegas, Paolo Maria Rossini, Camillo Marra, Peter Schonknecht, Tilman Hensch, KarlTitus Hoffmann, Joost Kuijer, Pieter Jelle Visser, Frederik Barkhof, Giovanni B. Frisoni, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; University of Trento, Trento, Italy; Service of Statistics, IRCCS Fatebenefratelli, Brescia, Italy; Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology