Die Habenula und motiviertes Verhalten des Menschen

Die Habenula, ein kleines Kerngebiet des Epithalamus, moduliert einen Hauptweg zur Top-Down-Kontrolle der monoaminergen Kerngebiete im HIrnstamm. Insbesondere die Ausschüttung von Dopamin und Serotonin im Telencephalon wird durch die Habenula beeinflusst. Bei Primaten spielt die Habenula eine wichtige Rolle bei der Handlungsüberwachung und rückmeldungsbasierten Entscheidungs- und Lernprozessen, speziell bei der Vermeidung von Handlungen mit negativem Ergebnis. Dysfunktionen der Habenula werden mit psychischen Störungen, z.B. der Depression, in Verbindung gebracht.
Das aktuelle Projekt fokussiert auf die Rolle der Habenula beim Vermeiden negativer Handlungsergebnisse. Dazu wird hochauflösende Bildgebung mittels MRT eingesetzt, um die Aktivierung und Konnektivität der Habenula bei Konditionierungs- und operanten Lernaufgaben zu untersuchen.

The human habenula and motivated behavior

In a changeable, uncertain environment it is necessary for goal-directed, motivated behavior to flexibly react to appetitive and aversive events and to learn from them in order to approach favorable situations and to avoid unfavorable ones. The neuromodulators dopamine (DA) and serotonin (5-HT) have been implicated in appetitive and aversive Pavlovian and instrumental learning and the associated behavioral responses. In the present proposal we focus on the habenula, a small epithalamic brain structure, which controls a major descending pathway from the forebrain to the mesencephalon thereby exerting strong influence on dopamine (DA) and serotonin (5-HT) release in the telencephalon. In primates it has been implicated in performance monitoring and value-based decision making, particularly in learning to avoid actions entailing losses or aversive outcomes. In humans, habenular dysfunction seems associated with psychiatric diseases, particularly major depressive disorder (MDD). However, knowledge about habenular function and connectivity in humans is sparse, because previous research has often neglected this small structure. The proposed project capitalizes on the increased accessibility of the human habenula due to advances in neuroimaging leading to higher signal-to-noise ratio at higher spatial resolution. It aims at understanding the role of the habenula in decision making with a focus on avoiding negative action outcomes. A converging methods approach will be applied to access the functional activity of the habenula and to unravel its anatomical and functional interaction with other brain regions implicated in motivated behavior: Using high-resolution functional magnetic resonance imaging in healthy volunteers, habenular activity and functional connectivity will be studied during rest, Pavlovian conditioning of rewarding and aversive events and during an instrumental probabilistic learning task allowing to disentangle approach- and avoidance-learning. By means of diffusion-weighted imaging (dwMRI) and probabilistic tractography individual connectivity profiles of the habenula with subcortical and cortical structures will be established. These connectivity profiles and other connectivity measures will be correlated with behavioral and neuroimaging data. In addition, the goal of this project phase is to establish behavioral and imaging protocols enabling a long-term research focus of the habenula in pathological states and in close relation to the neurochemistry orchestrated by this brain region.