Defining the habenula in human neuroimaging studies

Lawson, Rebecca; Drevets, Wayne C.; Roiser, Jonathan P.

doi:10.1016/j.neuroimage.2012.08.076

Cited by 106 publications

(136 citation statements)

References 39 publications

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“…S3). However, it is also worth noting that even with high-resolution fMRI, we do not have sufficient resolution to disambiguate the medial and lateral portions of the habenula, as outlined in our prior methodological paper on imaging the habenula in humans (9).…”

Section: Discussionmentioning

confidence: 99%

“…Statistical Parametric Mapping (SPM8; Wellcome Trust Centre for Neuroimaging, www.fil.ion.ucl.ac.uk/spm) was used to analyze all MRI data. For the ROI analysis of the habenula, each subject's data were slice time-corrected, realigned to the first image, unwarped using a field map of the static (B0) magnetic field (37), and coregistered to their individual anatomical scan, on which the habenula ROIs were placed according to a previously described procedure (9). Images were smoothed using a 2-mm FWHM Gaussian kernel to increase the signal-to-noise ratio without smoothing signal beyond the limits of the habenula ROI (9).…”

Section: Methodsmentioning

confidence: 99%

“…ROI definition. Habenula ROIs were placed manually for each subject in native space on high-resolution anatomical images according to a procedure previously described and validated (9). As a control region, the MD thalamus ROI was defined on the average normalized structural as a cylinder with a diameter of 4.5 mm that started on the same coronal slice as the habenula and continued anteriorly for 14 mm [approximately the length of the thalamus (43), including anterior and posterior MD thalamus regions], with the dorsolateral curve of the ROI following the dorsolateral edge of the MD thalamus against the third ventricle.…”

Section: Methodsmentioning

confidence: 99%

“…We then used these values in the fMRI analysis as parametric regressors whose onsets were timelocked to the presentation of win, loss, and shock CSs. Because our central hypothesis related to the habenula, and given the small size and potential interindividual anatomical variability of this structure, we manually defined regions of interest (ROIs) on high-resolution anatomical scans for the left and right habenula in each subject according to a previously established protocol (9). This, and the use of high-resolution functional scans, enabled us to avoid signal contamination from adjacent structures, such as the MD thalamus.…”

Section: Significancementioning

confidence: 99%

“…Prior fMRI investigations have been limited by the use of standard data acquisition protocols, in which a single image volume element (volumetric pixel or voxel) is typically as large as the habenula itself. This low resolution, exacerbated by substantial spatial smoothing during standard data processing, is likely to induce localization error (9), rendering a signal from the habenula difficult to resolve from adjacent structures, such as the medial dorsal (MD) nucleus of the thalamus (10)(11)(12). Here, by using high-resolution fMRI, in conjunction with computational modeling of reinforcement learning in a paradigm that included…”

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confidence: 99%

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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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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%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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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123

107

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Peril and Pleasure: An Rdoc-Inspired Examination of Threat Responses and Reward Processing in Anxiety and Depression

et al. 2013

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As a step toward addressing limitations in the current psychiatric diagnostic system, the NIMH recently developed the Research Domain Criteria (RDoC) to stimulate integrative research—spanning self-report, behavior, neural circuitry, and molecular/genetic mechanisms—on core psychological processes implicated in mental illness. Here, we use the RDoC conceptualization to review research on threat responses, reward processing, and their interaction. The first section of the manuscript highlights the pivotal role of exaggerated threat responses—mediated by circuits connecting the frontal cortex, amygdala, and midbrain—in anxiety, and reviews data indicating that genotypic variation in the serotonin system is associated with hyperactivity in this circuitry, which elevates the risk for anxiety and mood disorders. In the second section, we describe mounting evidence linking anhedonic behavior to deficits in psychological functions that rely heavily on dopamine signaling, especially cost/benefit decision-making and reward learning. The third section covers recent studies that document negative effects of acute threats and chronic stress on reward responses in humans. The mechanisms underlying such effects are unclear, but new optogenetic data in rodents indicate that GABAergic inhibition of midbrain dopamine neurons, driven by activation of the habenula, may play a fundamental role in stress-induced anhedonia. In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression.

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Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine

Wang

Chen

et al. 2021

Depression and Anxiety

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Background: Recently, an animal model for depression has shown that ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce.Methods: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis.Results: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders.Conclusions: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.

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Defining the habenula in human neuroimaging studies

Cited by 106 publications

References 39 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

Peril and Pleasure: An Rdoc-Inspired Examination of Threat Responses and Reward Processing in Anxiety and Depression

Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine

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