Habenula bibliometrics: Thematic development and research fronts of a resurgent field

Abstract

The habenula (Hb) is a small structure of the posterior diencephalon that is highly conserved across vertebrates but nonetheless has attracted relatively little research attention until the past two decades. The resurgent interest is motivated by neurobehavioral studies demonstrating critical functions in a broad spectrum of motivational and cognitive processes, including functions relevant to psychiatric diseases. The Hb is widely conceived as an “anti-reward” center that acts by regulating brain monoaminergic systems. However, there is still no general conceptual framework for habenula research, and no study has focused on uncovering potentially significant but overlooked topics that may advance our understanding of physiological functions or suggest potential clinical applications of Hb-targeted interventions. Using science mapping tools, we quantitatively and qualitatively analyzed the relevant publications retrieved from the Web of Science Core Collection (WoSCC) database from 2002 to 2021. Herein we present an overview of habenula-related publications, reveal primary research trends, and prioritize some key research fronts by complementary bibliometric analysis. High-priority research fronts include Ventral Pallidum, Nucleus Accumbens, Nicotine and MHb, GLT-1, Zebrafish, and GCaMP, Ketamine, Deep Brain Stimulation, and GPR139. The high intrinsic heterogeneity of the Hb, extensive connectivity with both hindbrain and forebrain structures, and emerging associations with all three dimensions of mental disorders (internalizing, externalizing, and psychosis) suggest that the Hb may be the neuronal substrate for a common psychopathology factor shared by all mental illnesses termed the p factor. A future challenge is to explore the therapeutic potential of habenular modulation at circuit, cellular, and molecular levels.

The Habenula in Mood Disorders: A Scoping Review of Human Studies

“…While there exists a large body of animal research devoted to studying the LHb, relatively little is known about the MHb (Viswanath et al, 2014). Over the past 2 decades, the LHb has garnered growing attention (Chen et al, 2022), largely because of its proposed role in mood disorders and especially in depression (Hu et al, 2020). The idea that the LHb plays a role in mood disorders arose from two major streams of research in animal models.…”

Design and Synthesis of Novel GPR139 Agonists with Therapeutic Effects in Mouse Models of Social Interaction and Cognitive Impairment

“…The habenula is an evolutionarily conserved brain nucleus that regulates monoaminergic systems, notably dopamine and serotonin, and integrates cognitive with emotional and sensory processing. − It comprises two subnuclei, the lateral (LHb) and medial habenula (MHb). Previous findings suggest the dysfunction of the MHb is potentially associated with various mental disorders, such as schizophrenia and attention-deficit/hyperactivity disorder. − The LHb plays a crucial role in aversion, negative rewards, stress, and cognitive processing, and its dysfunction is related to multiple psychiatric disorders, such as major depression .…”