Lesions of lateral habenula attenuate win-stay but not lose-shift responses in a competitive choice task

Thapa, Rajat; Donovan, Clifford H.; Wong, Scott A.; Sutherland, Robert J.; Gruber, Aaron J.

doi:10.1016/j.neulet.2018.10.056

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…In rodents, lose-shift behavior depends on the lateral striatum, a sensorimotor region approximately homologous to the primate dorsolateral putamen. In contrast, win-stay rodent behavior depends on the ventromedial striatum and lateral habenula . Interestingly, however, human lose-shift responding increases under cognitive load, suggesting that frontoparietal control may suppress automatic, striatum-mediated lose-shifts .…”

Section: Discussionmentioning

confidence: 92%

“…In contrast, win-stay rodent behavior depends on the ventromedial striatum and lateral habenula. Interestingly, however, human lose-shift responding increases under cognitive load, suggesting that frontoparietal control may suppress automatic, striatum-mediated lose-shifts. During exploration and learning in continuous spaces, dynamic maps of competing options are found in frontoparietal circuits, specifically the dorsal stream and caudal posterior parietal cortex .…”

Section: Discussionmentioning

confidence: 99%

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Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression

Tsypes,

Hallquist,

Ianni

et al. 2024

JAMA Psychiatry

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ImportanceClinical theory and behavioral studies suggest that people experiencing suicidal crisis are often unable to find constructive solutions or incorporate useful information into their decisions, resulting in premature convergence on suicide and neglect of better alternatives. However, prior studies of suicidal behavior have not formally examined how individuals resolve the tradeoffs between exploiting familiar options and exploring potentially superior alternatives.ObjectiveTo investigate exploration and exploitation in suicidal behavior from the formal perspective of reinforcement learning.Design, Setting, and ParticipantsTwo case-control behavioral studies of exploration-exploitation of a large 1-dimensional continuous space and a 21-day prospective ambulatory study of suicidal ideation were conducted between April 2016 and March 2022. Participants were recruited from inpatient psychiatric units, outpatient clinics, and the community in Pittsburgh, Pennsylvania, and underwent laboratory and ambulatory assessments. Adults diagnosed with borderline personality disorder (BPD) and midlife and late-life major depressive disorder (MDD) were included, with each sample including demographically equated groups with a history of high-lethality suicide attempts, low-lethality suicide attempts, individuals with BPD or MDD but no suicide attempts, and control individuals without psychiatric disorders. The MDD sample also included a subgroup with serious suicidal ideation.Main Outcomes and MeasuresBehavioral (model-free and model-derived) indices of exploration and exploitation, suicide attempt lethality (Beck Lethality Scale), and prospectively assessed suicidal ideation.ResultsThe BPD group included 171 adults (mean [SD] age, 30.55 [9.13] years; 135 [79%] female). The MDD group included 143 adults (mean [SD] age, 62.03 [6.82] years; 81 [57%] female). Across the BPD (χ23 = 50.68; P &lt; .001) and MDD (χ24 = 36.34; P &lt; .001) samples, individuals with high-lethality suicide attempts discovered fewer options than other groups as they were unable to shift away from unrewarded options. In contrast, those with low-lethality attempts were prone to excessive behavioral shifts after rewarded and unrewarded actions. No differences were seen in strategic early exploration or in exploitation. Among 84 participants with BPD in the ambulatory study, 56 reported suicidal ideation. Underexploration also predicted incident suicidal ideation (χ21 = 30.16; P &lt; .001), validating the case-control results prospectively. The findings were robust to confounds, including medication exposure, affective state, and behavioral heterogeneity.Conclusions and RelevanceThe findings suggest that narrow exploration and inability to abandon inferior options are associated with serious suicidal behavior and chronic suicidal thoughts. By contrast, individuals in this study who engaged in low-lethality suicidal behavior displayed a low threshold for taking potentially disadvantageous actions.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression

Tsypes,

Hallquist,

Ianni

et al. 2024

JAMA Psychiatry

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“…16 Lesions of the LHb significantly decreased a winstay strategy but did not affect lose-shift strategy in a competitive choice task. 17 Additionally, the LHb has been found to be involved in fear learning and memory. 18 Chemogenetic inhibition of rat LHb during conditioning reduced subsequent freezing to contextual cues, but increased freezing in response to discrete cues associated with an aversive stimulus (footshock).…”

Section: Introductionmentioning

confidence: 99%

“…Inactivation of the LHb causes trained rats to perform at a chance level in a tone‐directed maze task, indicating the LHb's involvement in adaptive learning and decision making 16 . Lesions of the LHb significantly decreased a win‐stay strategy but did not affect lose‐shift strategy in a competitive choice task 17 . Additionally, the LHb has been found to be involved in fear learning and memory 18 .…”

Section: Introductionmentioning

confidence: 99%

PACAP‐expressing neurons in the lateral habenula diminish negative emotional valence

Levinstein

Bergkamp

Lewis

et al. 2022

Genes Brain and Behavior

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The lateral habenula (LHb) is a small, bilateral, epithalamic nucleus which processes aversive information. While primarily glutamatergic, LHb neurons express genes coding for many neuropeptides, such as Adcyap1 the gene encoding pituitary adenylate cyclase‐activating polypeptide (PACAP), which itself has been associated with anxiety and stress disorders. Using Cre‐dependent viral vectors, we targeted and characterized these neurons based on their anatomical projections and found that they projected to both the raphe and rostromedial tegmentum but only weakly to ventral tegmental area. Using RiboTag to capture ribosomal‐associated mRNA from these neurons and reanalysis of existing single cell RNA sequencing data, we did not identify a unique molecular phenotype that characterized these PACAP‐expressing neurons in LHb. In order to understand the function of these neurons, we conditionally expressed hM3Dq DREADD selectively in LHb PACAP‐expressing neurons and chemogenetically excited these neurons during behavioral testing in the open field test, contextual fear conditioning, sucrose preference, novelty suppressed feeding, and conditioned place preference. We found that Gq activation of these neurons produce behaviors opposite to what is expected from the LHb as a whole—they decreased anxiety‐like and fear behavior and produced a conditioned place preference. In conclusion, PACAP‐expressing neurons in LHb represents a molecularly diverse population of cells that oppose the actions of the remainder of LHb neurons by being rewarding or diminishing the negative consequences of aversive events.

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Effects of environmental enrichment on exploratory behavior, win-stay and lose-shift performance, motor sequence learning, and reversal learning during the three-lever operant task in mice

Kikuchi

Yoneda

Nishikawa

et al. 2022

Behavioural Brain Research

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Lesions of lateral habenula attenuate win-stay but not lose-shift responses in a competitive choice task

Cited by 6 publications

References 30 publications

Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression

Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression

PACAP‐expressing neurons in the lateral habenula diminish negative emotional valence

Effects of environmental enrichment on exploratory behavior, win-stay and lose-shift performance, motor sequence learning, and reversal learning during the three-lever operant task in mice

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