Habenula Volume in Bipolar Disorder and Major Depressive Disorder: A High-Resolution Magnetic Resonance Imaging Study

Savitz, Jonathan; Nugent, Allison C.; Bogers, Wendy; Roiser, Jonathan P.; Bain, Earle; Neumeister, Alexander; Zarate, Carlos A.; Manji, Husseini K.; Cannon, Dara M.; Marrett, Sean; Henn, Fritz A.; Charney, Dennis S.; Drevets, Wayne C.

doi:10.1016/j.biopsych.2010.09.027

Cited by 166 publications

(167 citation statements)

References 24 publications

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“…This link with the invigoration and suppression of behavior hints at a potential role for the habenula in disorders characterized by aberrant motivated behavior, such as depression. Abnormalities in habenula structure and function have been reported in depressed patients (29,30), as well as in animal models (31). Additionally, a recent study reported that glucose metabolism in the vicinity of the habenula decreased in depressed patients following treatment with ketamine (32).…”

Section: Discussionmentioning

confidence: 99%

The habenula encodes negative motivational value associated with primary punishment in humans

Lawson

Seymour

Loh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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126

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Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trialby-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.high-resolution fMRI | conditioned behavior | pallidum L earning which stimuli predict positive and negative outcomes, and thus should be approached or avoided, respectively, is central to an organism's ability to survive. Midbrain dopamine neurons respond to both unpredicted rewarding stimuli and to cues previously paired with rewards (1), consistent with behavioral approach toward those cues. As a counterpoint to these reward-related signals, neurons in the lateral habenula (LHb) of nonhuman primates respond to previously learned stimuli predicting the delivery of punishments and the omission of rewards, whereas they are inhibited by stimuli that signal upcoming rewards (2). These studies in nonhuman primates have concentrated on well-learned stimuli, and so have forsaken the opportunity to study the details of dynamic adaptation in the habenula. However, in many real-world scenarios, organisms learn about the motivational value of novel cues in their environment gradually, one exposure at a time, which raises the question as to whether the habenula plays a role in encoding the dynamically changing motivational value of cues that predict negative events.Dynamic learning from aversive events permits the rapid experience-dependent updating of behavior, for example, the automatic suppression of approach, which is a characteristic of aversive conditioning (3). The LHb receives inputs from the globus pallidus (4), and its excitation inhibits midbrain dopamine neurons via the rostromedial tegmental nucleus (2). This position as a hub between corticolimbic networks and midbrain monoaminergic nuclei provides a means through which positively or negatively valenced stimuli can modulate motor output, leading to the hypothesis that the habenula plays a critical role in motivated behavior (5).Studies using temporally precise optogenetic stimulation of the LHb in rodents provide convincing evidence that the habenula drives behavioral suppression (6). This structure has been suggested as a novel target for de...

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Section: Discussionmentioning

confidence: 99%

The habenula encodes negative motivational value associated with primary punishment in humans

Lawson

Seymour

Loh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

126

110

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“…Accordingly, this neural network indicates that the Hb may act as a hub between forebrain and midbrain regions, together with its implication in a wide range of behaviors such as sleep-wake cycles, olfaction, ingestion, sexual behavior, stress response, reward-punishment, and pain and analgesia (Thornton et al 1985;Sugama et al 2002;Hikosaka 2010). The Hb has also been linked to various psychiatric disorders such as anxiety and depression (Savitz et al 2011a(Savitz et al , 2011b(Savitz et al , 2013, which are commonly comorbid disorders with chronic pain conditions. The role of the Hb in pain processing is well documented in animals (reviewed in Shelton et al 2012a), as well as in imaging studies of acute experimental pain in humans (Shelton et al 2012b).…”

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confidence: 94%

Habenula functional resting-state connectivity in pediatric CRPS

Erpelding

Sava

Simons

et al. 2014

Journal of Neurophysiology

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The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10–17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

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“…Regarding the hippocampus, some studies reported increased volume [136] as well as decreased volume [119,137]. By contrast, reports of gray matter abnormalities for dorsolateral prefrontal cortex [118,134,[138][139][140] and the habenula [141] have been infrequent but show a more consistent pattern of reduced volume. For the orbitofrontal cortex, decreased volume [117,134,142] and neuronal size reduction [143] have been reported, in addition to no alterations [144].…”

Section: Gray Matter Alterationsmentioning

confidence: 96%

Emotional and Motivational Processes in Bipolar Disorder: A Neural Network Perspective

Wessa¹,

Linke²

2013

Psychiatric Disorders - New Frontiers in Affective Disorders

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Habenula Volume in Bipolar Disorder and Major Depressive Disorder: A High-Resolution Magnetic Resonance Imaging Study

Abstract: Background-Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present at postmortem. We conducted the first MRI analysis of habenula volume in MDD and bipolar disorder (BD).

Cited by 166 publications

References 24 publications

The habenula encodes negative motivational value associated with primary punishment in humans

The habenula encodes negative motivational value associated with primary punishment in humans

Habenula functional resting-state connectivity in pediatric CRPS

Emotional and Motivational Processes in Bipolar Disorder: A Neural Network Perspective

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