Altered Neural Responses to Punishment Learning in Conduct Disorder

Erik M. Elster; Ruth Pauli; Graeme Fairchild; Maria McDonald; Sarah Baumann; Justina Sidlauskaite; Stephane De Brito; Christine M. Freitag; Kerstin Konrad; Veit Roessner; Inti A. Brazil; Patricia L. Lockwood; Gregor Kohls

doi:10.1016/j.bpsc.2025.01.003

Altered Neural Responses to Punishment Learning in Conduct Disorder

Erik M. Elster, Ruth Pauli, Graeme Fairchild, Maria McDonald, Sarah Baumann, Justina Sidlauskaite, Stephane De Brito, Christine M. Freitag, Kerstin Konrad, Veit Roessner, Inti A. Brazil, Patricia L. Lockwood, Gregor Kohls

Research output: Contribution to journal › Article › peer-review

3 Citations (SciVal)

Abstract

Background: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared with typically developing control participants (TDCs).

Methods: A total of 75 youths with CD and 99 TDCs (9–18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate α), we investigated group differences for the 3 learning conditions in whole-brain and region of interest (ROI) analyses, including the ventral striatum and insula.

Results: Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in participants with CD compared with TDCs.

Conclusions: Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD that contributes to punishment insensitivity/hyposensitivity as a hallmark of the disorder. Because the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.

Original language	English
Pages (from-to)	936-943
Number of pages	8
Journal	Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume	10
Issue number	9
Early online date	11 Jan 2025
DOIs	https://doi.org/10.1016/j.bpsc.2025.01.003
Publication status	Published - Sept 2025

Funding

This work was supported by the European Commission's Seventh Framework Programme (Grant No. 602407 [FemNAT-CD; coordinator: CMF]). GK and EME were supported by a 2023 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant No. 30849 [principal investigator, GK]). RP was supported by an ESRC postdoctoral fellowship award (Fellowship No. ES/V011324/1). PLL was supported by a Jacobs Foundation Research Fellowship, a Leverhulme Prize (Fellowship No. PLP-2021-196), a Wellcome Trust/Royal Society Sir Henry Dale Fellowship (Fellowship No. 223264/Z/21/Z), and a UKRI EPSRC Frontiers Research Guarantee/ERC Starting Grant (Grant No. EP/X020215/1). IAB was supported by a VIDI grant awarded by the Dutch Research Council (Grant No. VI.Vidi.2021G.017). SDB was supported by an ESRC grant (Grant No. ES/V003526/1). The project was funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) as part of the German Center for Child and Adolescent Health (Grant No. 01GL2405B). We thank the Federal Ministry of Education and Research and the state governments (http://www.nhr-verein.de/unsere-partner) for supporting this study as part of the joint funding of National High-Performance Computing. Furthermore, we thank Professor Stefan Ehrlich and the members of his group, especially Arne Doose, for their feedback on the model-based fMRI analysis. We also thank Dr. Josefine Rothe, who was partially funded by a Brain & Behavior Research Foundation grant (Grant No. 30849 [principal investigator, GK]). CMF receives royalties for books on attention-deficit/hyperactivity disorder, autism spectrum disorder, and major depressive disorder. All other authors report no biomedical financial interests or potential conflicts of interest. This work was supported by the European Commission’s Seventh Framework Programme (Grant No. 602407 [FemNAT-CD; coordinator: CMF]). GK and EME were supported by a 2023 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Grant No. 30849 [principal investigator, GK]). RP was supported by an ESRC postdoctoral fellowship award (Fellowship No. ES/V011324/1). PLL was supported by a Jacobs Foundation Research Fellowship, a Leverhulme Prize (Fellowship No. PLP-2021-196), a Wellcome Trust / Royal Society Sir Henry Dale Fellowship (Fellowship No. 223264/Z/21/Z), and a UKRI EPSRC Frontiers Research Guarantee/ERC Starting Grant (Grant No. EP/X020215/1). IAB was supported by a VIDI grant awarded by the Dutch Research Council (Grant No. VI.Vidi.2021G.017). SDB was supported by an ESRC grant (Grant No. ES/V003526/1). The project was funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) as part of the German Center for Child and Adolescent Health (Grant No. 01GL2405B). We thank the Federal Ministry of Education and Research and the state governments ( http://www.nhr-verein.de/unsere-partner ) for supporting this study as part of the joint funding of National High-Performance Computing. Furthermore, we thank Professor Stefan Ehrlich and the members of his group, especially Arne Doose, for their feedback on the model-based fMRI analysis. We also thank Dr. Josefine Rothe, who was partially funded by a Brain & Behavior Research Foundation grant (Grant No. 30849 [principal investigator, GK]).

Funders	Funder number
The Wellcome Trust
California Missions Foundation
Jacobs Foundation
National Alliance for Research on Schizophrenia and Depression
Seventh Framework Programme	602407
Leverhulme Prize	PLP-2021-196
Brain and Behavior Research Foundation	30849
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	ES/V003526/1
Engineering and Physical Sciences Research Council	EP/X020215/1
Royal Society	223264/Z/21/Z
Bundesministerium für Bildung und Forschung	01GL2405B
Economic and Social Research Council	ES/V011324/1

Keywords

Computational modeling
Conduct disorder
fMRI
Insula
Punishment
Reinforcement learning

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Cognitive Neuroscience
Clinical Neurology
Biological Psychiatry

Access to Document

10.1016/j.bpsc.2025.01.003Licence: CC BY

Cite this

Elster, E. M., Pauli, R., Fairchild, G., McDonald, M., Baumann, S., Sidlauskaite, J., De Brito, S., Freitag, C. M., Konrad, K., Roessner, V., Brazil, I. A., Lockwood, P. L., & Kohls, G. (2025). Altered Neural Responses to Punishment Learning in Conduct Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 10(9), 936-943. https://doi.org/10.1016/j.bpsc.2025.01.003

Elster, EM, Pauli, R, Fairchild, G, McDonald, M, Baumann, S, Sidlauskaite, J, De Brito, S, Freitag, CM, Konrad, K, Roessner, V, Brazil, IA, Lockwood, PL & Kohls, G 2025, 'Altered Neural Responses to Punishment Learning in Conduct Disorder', Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 10, no. 9, pp. 936-943. https://doi.org/10.1016/j.bpsc.2025.01.003

@article{d41aace9f35d47c88c0b3e28dc7fc1a6,

title = "Altered Neural Responses to Punishment Learning in Conduct Disorder",

abstract = "Background: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared with typically developing control participants (TDCs). Methods: A total of 75 youths with CD and 99 TDCs (9–18 years, 47\% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate α), we investigated group differences for the 3 learning conditions in whole-brain and region of interest (ROI) analyses, including the ventral striatum and insula. Results: Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in participants with CD compared with TDCs. Conclusions: Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD that contributes to punishment insensitivity/hyposensitivity as a hallmark of the disorder. Because the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.",

keywords = "Computational modeling, Conduct disorder, fMRI, Insula, Punishment, Reinforcement learning",

author = "Elster, \{Erik M.\} and Ruth Pauli and Graeme Fairchild and Maria McDonald and Sarah Baumann and Justina Sidlauskaite and \{De Brito\}, Stephane and Freitag, \{Christine M.\} and Kerstin Konrad and Veit Roessner and Brazil, \{Inti A.\} and Lockwood, \{Patricia L.\} and Gregor Kohls",

year = "2025",

month = sep,

doi = "10.1016/j.bpsc.2025.01.003",

language = "English",

volume = "10",

pages = "936--943",

journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",

issn = "2451-9022",

publisher = "Elsevier",

number = "9",

}

TY - JOUR

T1 - Altered Neural Responses to Punishment Learning in Conduct Disorder

AU - Elster, Erik M.

AU - Pauli, Ruth

AU - Fairchild, Graeme

AU - McDonald, Maria

AU - Baumann, Sarah

AU - Sidlauskaite, Justina

AU - De Brito, Stephane

AU - Freitag, Christine M.

AU - Konrad, Kerstin

AU - Roessner, Veit

AU - Brazil, Inti A.

AU - Lockwood, Patricia L.

AU - Kohls, Gregor

PY - 2025/9

Y1 - 2025/9

N2 - Background: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared with typically developing control participants (TDCs). Methods: A total of 75 youths with CD and 99 TDCs (9–18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate α), we investigated group differences for the 3 learning conditions in whole-brain and region of interest (ROI) analyses, including the ventral striatum and insula. Results: Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in participants with CD compared with TDCs. Conclusions: Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD that contributes to punishment insensitivity/hyposensitivity as a hallmark of the disorder. Because the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.

AB - Background: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared with typically developing control participants (TDCs). Methods: A total of 75 youths with CD and 99 TDCs (9–18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies. Using fMRI data in conjunction with computational modeling indices (learning rate α), we investigated group differences for the 3 learning conditions in whole-brain and region of interest (ROI) analyses, including the ventral striatum and insula. Results: Whole-brain analysis revealed typical neural responses for RL in both groups. However, linear regression models for the ROI analyses revealed that only the response pattern of the (anterior) insula during punishment learning was different in participants with CD compared with TDCs. Conclusions: Youths with CD have atypical neural responses to learning from punishment (but not from reward), specifically in the insula. This suggests a selective dysfunction of RL mechanisms in CD that contributes to punishment insensitivity/hyposensitivity as a hallmark of the disorder. Because the (anterior) insula is involved in avoidance behaviors related to negative affect or arousal, insula dysfunction in CD may contribute to inappropriate behavioral decision making, which increases the risk for reckless, antisocial, and aggressive behaviors in affected youth.

KW - Computational modeling

KW - Conduct disorder

KW - fMRI

KW - Insula

KW - Punishment

KW - Reinforcement learning

UR - https://www.scopus.com/pages/publications/105001481228

U2 - 10.1016/j.bpsc.2025.01.003

DO - 10.1016/j.bpsc.2025.01.003

M3 - Article

C2 - 39805552

AN - SCOPUS:105001481228

SN - 2451-9022

VL - 10

SP - 936

EP - 943

JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

IS - 9

ER -

Altered Neural Responses to Punishment Learning in Conduct Disorder

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this