Blunted Ventral Striatal Reactivity to Social Reward Is Associated with More Severe Motivation and Pleasure Deficits in Psychosis

Schizophrenia Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract Background and Hypothesis Among individuals living with psychotic disorders, social impairment is common, debilitating, challenging to treat. While the roots of this are undoubtedly complex, converging lines evidence suggest that motivation pleasure (MAP) deficits play a central role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences. Study Design Here we leveraged parallel incentive delay functional magnetic resonance imaging paradigms test whether blunted reactivity incentives in ventral striatum—a key component distributed neural circuit mediating appetitive hedonic pleasure—is associated more severe MAP symptoms transdiagnostic adult sample enriched for psychosis. To maximize ecological validity translational relevance, capitalized naturalistic audiovisual clips an established partner expressing positive feedback. Results Although both robustly engaged striatum, only was clinician-rated deficits. This association remained significant when controlling other symptoms, binary diagnostic status, or striatal incentives. Follow-up analyses suggested predominantly reflects diminished activation during presentation reward. Conclusions These observations provide neurobiologically grounded framework conceptualizing social-anhedonia impairments characterize many disorders underscore need develop targeted intervention strategies.

Language: Английский

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An Honest Reckoning With the Amygdala and Mental Illness

American Journal of Psychiatry, Journal Year: 2024, Volume and Issue: 181(12), P. 1059 - 1075

Published: Dec. 1, 2024

Anxiety disorders are a leading source of human misery, morbidity, and premature mortality. Existing treatments far from curative for many, underscoring the need to clarify underlying neural mechanisms. Although many brain regions contribute, amygdala has received most intense scientific attention. Over past several decades, this scrutiny yielded detailed understanding function, but it failed produce new clinical assays, biomarkers, or cures. Rising urgent public health challenge demands an honest reckoning with functional-neuroanatomical complexity shift theories anchored on "the amygdala" models centered specific nuclei cell types. This review begins by examining evidence studies rodents, monkeys, humans "canonical model," idea that plays central role in fear- anxiety-related states, traits, disorders. Next, authors selectively highlight work indicating canonical model, while true, is overly simplistic fails adequately capture actual state evidentiary record, breadth amygdala-associated functions illnesses, amygdala's functional architecture. The describe implications these facts basic neuroimaging research. concludes some general recommendations grappling accelerating efforts understand more effectively treat amygdala-related psychopathology.

Language: Английский

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Neuroticism/Negative Emotionality Is Associated with Increased Reactivity to Uncertain Threat in the Bed Nucleus of the Stria Terminalis, Not the Amygdala

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(32), P. e1868232024 - e1868232024

Published: July 15, 2024

Neuroticism/negative emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, well-being. Elevated N/NE is associated panoply adverse outcomes, from reduced socioeconomic attainment psychiatric illness. Animal research suggests that reflects heightened reactivity uncertain threat in the bed nucleus stria terminalis (BST) central amygdala (Ce), but relevance these discoveries humans has remained unclear. Here we used novel combination psychometric, psychophysiological, neuroimaging approaches test this hypothesis an ethnoracially diverse, sex-balanced sample 220 emerging adults selectively recruited encompass broad spectrum N/NE. Cross-validated robust-regression analyses demonstrated preferentially BST activation during anticipation genuinely distressing (aversive multimodal stimulation), whereas was unrelated certain-threat anticipation, Ce either type or BST/Ce threat-related faces. It often assumed different paradigms are interchangeable assays individual differences brain function, yet rarely been tested. Our results revealed negligible associations between presentation faces, indicating two tasks nonfungible. These observations provide framework conceptualizing emotional traits disorders; guiding design interpretation biobank studies risk, disease, treatment; refining mechanistic research.

Language: Английский

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Neuroticism/negative emotionality is associated with increased reactivity to uncertain threat in the bed nucleus of the stria terminalis, not the amygdala

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 10, 2023

Neuroticism/Negative Emotionality (N/NE)-the tendency to experience anxiety, fear, and other negative emotions-is a fundamental dimension of temperament with profound consequences for health, wealth, wellbeing. Elevated N/NE is associated panoply adverse outcomes, from reduced socioeconomic attainment psychiatric illness. Animal research suggests that reflects heightened reactivity uncertain threat in the bed nucleus stria terminalis (BST) central amygdala (Ce), but relevance these discoveries humans has remained unclear. Here we used novel combination psychometric, psychophysiological, neuroimaging approaches rigorously test this hypothesis an ethnoracially diverse, sex-balanced sample 220 emerging adults selectively recruited encompass broad spectrum N/NE. Cross-validated robust-regression analyses demonstrated preferentially BST activation during anticipation genuinely distressing (aversive multimodal stimulation), whereas was unrelated certain-threat anticipation, Ce either type or BST/Ce threat-related faces. It often assumed different paradigms are interchangeable assays individual differences brain function, yet rarely been tested. Our results revealed negligible associations between presentation faces, indicating two tasks non-fungible. These observations provide framework conceptualizing emotional traits disorders; guiding design interpretation biobank studies risk, disease, treatment; informing mechanistic research.

Language: Английский

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Blunted ventral striatal reactivity to social reward is associated with more severe motivation and pleasure deficits in psychosis.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this are undoubtedly complex, converging lines evidence suggest that motivation pleasure (MAP) deficits play a key role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences. Here we leveraged parallel incentive delay fMRI paradigms test whether blunted reactivity incentives in ventral striatum—a component distributed neural circuit mediating appetitive hedonic pleasure—is associated more severe MAP symptoms transdiagnostic sample enriched for psychosis. To maximize ecological validity translational relevance, capitalized naturalistic audiovisual clips an established partner expressing positive feedback. Although both robustly engaged striatum, only was clinician-rated deficits. This association remained significant when controlling other symptoms, binary diagnostic status, or striatum incentives. Follow-up analyses suggested predominantly reflects diminished striatal activation during receipt reward. These observations provide neurobiologically grounded framework conceptualizing social-anhedonia impairments characterize many disorders underscore need establish targeted intervention strategies.

Language: Английский

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A shared threat-anticipation circuit is dynamically engaged at different moments by certain and uncertain threat

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Temporal dynamics play a central role in models of emotion: "fear" is widely conceptualized as phasic response to certain-and-imminent danger, whereas "anxiety" sustained uncertain-or-distal harm. Yet the underlying neurobiology remains contentious. Leveraging translationally relevant fMRI paradigm and theory-driven modeling approach, we demonstrate that certain- uncertain-threat anticipation recruit shared circuit encompasses extended amygdala (EAc), periaqueductal gray, midcingulate, anterior insula. This exhibits persistently elevated activation when threat uncertain distal, transient bursts just before certain encounters with threat. Although there widespread agreement EAc plays critical orchestrating responses threat, confusion persists about respective contributions its major subdivisions, bed nucleus stria terminalis (BST) (Ce). Here used anatomical regions-of-interest BST Ce exhibit statistically indistinguishable dynamics, moderate-to-strong Bayesian evidence for null hypothesis. Both regions exhibited run counter popular models, showing uncertain-and-distal For many scientists, feelings are hallmark fear anxiety. an independently validated brain "signature" covertly decode moment-by-moment anticipatory distress first time. Results mirrored neural activation. These observations provide fresh insights into threat-elicited emotions set stage more ambitious clinical mechanistic research.

Language: Английский

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Adolescent social anxiety is associated with diminished discrimination of anticipated threat and safety

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

ABSTRACT Social anxiety—which typically emerges in adolescence—lies on a continuum and, when extreme, can be devastating. Socially anxious individuals are prone to heightened fear, anxiety, and the avoidance of contexts associated with potential social scrutiny. Yet most neuroimaging research has focused acute threat. Much less attention been devoted understanding neural systems recruited during uncertain anticipation encounters Here we used novel fMRI paradigm probe circuitry engaged presentation threatening faces voices racially diverse sample 66 adolescents selectively encompass range anxiety enriched for clinically significant levels distress impairment. Results demonstrated that more severe symptoms experience anticipating threat, reduced discrimination threat safety bed nucleus stria terminalis (BST), key division central extended amygdala (EAc). Although EAc—including BST amygdala—was robustly by voices, degree EAc engagement was unrelated severity anxiety. Together, these observations provide neurobiologically grounded framework conceptualizing adolescent set stage kinds prospective-longitudinal mechanistic will necessary determine causation ultimately, develop improved interventions this often-debilitating illness.

Language: Английский

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