Mapping Reward Circuits: Orbitofrontal-Accumben Tracts and Their Links to Psychopathological Traits
Presented During:
Saturday, June 28, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M3 (Mezzanine Level)
Poster No:
629
Submission Type:
Abstract Submission
Authors:
Santiago Mezzano1, Tobias Brokel2, Veronica Orbecchi2, Manu Raghavan2, Ahmad Beyh2, Flavio Dell'Acqua2
Institutions:
1NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience., London, United Kingdom, 2NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience., London, London
First Author:
Santiago Mezzano
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, United Kingdom
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, United Kingdom
Co-Author(s):
Tobias Brokel
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
Veronica Orbecchi
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
Manu Raghavan
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
Ahmad Beyh
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
Flavio Dell'Acqua
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
NatBrainLab, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience.
London, London
Introduction:
Dysfunction in reward-related brain circuits, particularly involving the orbitofrontal cortex (OFC) and its projections to the nucleus accumbens (NAcc), have been implicated in various psychopathologies, including depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) ( Kujawa, 2019). The OFC is structurally, and functionally divided into the medial OFC (mOFC) and lateral OFC (lOFC), with the mOFC primarily involved in processing rewards and the lOFC associated with non-reward or punishment sensitivity (Rolls, 2019). These divisions influence goal-directed behavior and emotional regulation through their White Matter (WM) connectivity with the NAcc (Haber, 2012). Despite extensive functional imaging evidence, the structural underpinnings of these pathways remains unexplored. This study investigates the structural associations of lOFC-NAcc and mOFC-NAcc tracts to psychopathological scores, using diffusion MRI data from healthy subjects from the Human Connectome Project (HCP) (Van Essen, 2013).
Methods:
High-resolution diffusion-weighted imaging data from 166 participants (aged 22-35, 53% male) were pre-processed (MP-PCA denoising, Gibbs ringing, distortion, motion and eddy current corrections). Then, tractography was processed with a spherical deconvolution algorithm using Startrack (Dell'Acqua, 2010). MegaTrack, a novel tractography segmentation tool (Dell'Acqua, 2015) enabled efficient and unbiased tract segmentation by aligning tractograms into a common standard space for a single manual dissection. This dissection was then mapped back to native space, allowing for precise diffusion and tractography metrics extraction for each subject. Virtual dissection identified four bilateral pathways connecting the lOFC and mOFC to the NAcc (figure 2), with ROIs derived from the DKT atlas (Desikan, 2006).
Microstructural metrics extracted were fractional anisotropy (FA), hindered modulus of anisotropy (HMOA) (Dell'Acqua 2013), and tract volume. An mOFC/lOFC ratio was computed. Psychopathological traits were measured using HCP Achenbach Adult Self-Report DSM-oriented scores (Achenbach, 2003). Correlation analyses and multiple linear regression, adjusted for age and gender, evaluated associations between tract metrics and psychopathological scores.
Microstructural metrics extracted were fractional anisotropy (FA), hindered modulus of anisotropy (HMOA) (Dell'Acqua 2013), and tract volume. An mOFC/lOFC ratio was computed. Psychopathological traits were measured using HCP Achenbach Adult Self-Report DSM-oriented scores (Achenbach, 2003). Correlation analyses and multiple linear regression, adjusted for age and gender, evaluated associations between tract metrics and psychopathological scores.
Results:
The FA of lOFC-NAcc pathways positively correlated with total psychopathological traits, while mOFC-NAcc FA showed a negative correlation. A lOFC/mOFC ratio emerged as a stronger predictor of psychopathology than individual tracts (Figure 1A). Multiple linear regression analyses and random split-half testing further supported the significant association of the OFC ratio with psychopathological traits.
To gain greater specificity into psychopathological traits, we analyzed their DSM derived subtypes and found that the FA ratio was significantly associated with depression, somatic problems, avoidant personality traits, and ADHD, with all associations surviving FDR correction (Figure 1B). Additionally, other analyses revealed specific links between the lOFC/mOFC ratio and inattention traits in ADHD (R = 0.226, p = 0.0036), but not hyperactivity.
Notably, this ratio demonstrated significant lateralization, with stronger associations in the left hemisphere, suggesting hemispheric specialization in reward processing.
To gain greater specificity into psychopathological traits, we analyzed their DSM derived subtypes and found that the FA ratio was significantly associated with depression, somatic problems, avoidant personality traits, and ADHD, with all associations surviving FDR correction (Figure 1B). Additionally, other analyses revealed specific links between the lOFC/mOFC ratio and inattention traits in ADHD (R = 0.226, p = 0.0036), but not hyperactivity.
Notably, this ratio demonstrated significant lateralization, with stronger associations in the left hemisphere, suggesting hemispheric specialization in reward processing.
Conclusions:
This study provides some promising evidence of structural distinctions between lOFC-NAcc and mOFC-NAcc pathways in relation to psychopathology. Particularly, findings align with the non-reward attractor theory of depression, and could suggest that the lOFC/mOFC ratio serves as a sensitive marker of reward and punishment dysfunction. The observed lateralization effects underscore the need to consider hemispheric differences in reward processing networks. Future investigations should validate these findings in clinical populations and explore their utility for psychiatric translation.
Emotion, Motivation and Social Neuroscience:
Reward and Punishment 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Novel Imaging Acquisition Methods:
Diffusion MRI
Keywords:
Basal Ganglia
Cognition
Emotions
MRI
Open Data
Psychiatric
Tractography
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Provide references using APA citation style.
Cheng, W. (2016). Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression. Brain, 139(12), 3296-3309. https://doi.org/10.1093/brain/aww255
Dell’Acqua, F. (2010). A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution. NeuroImage, 49(2), 1446-1458. https://doi.org/10.1016/j.neuroimage.2009.09.033
Dell’Acqua, F. (2013). Tractography-based parcellation of the cortex using diffusion MRI: Methodological aspects and applications. Frontiers in Neuroanatomy, 7, 24. https://doi.org/10.3389/fnana.2013.00024
Desikan, R. S. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968-980. https://doi.org/10.1016/j.neuroimage.2006.01.021
Haber, S. N. (2012). The primate basal ganglia: Parallel and integrative networks. Journal of Chemical Neuroanatomy, 42(4), 221-230. https://doi.org/10.1016/j.jchemneu.2011.08.013
Kujawa, A. (2019). Reduced reward responsiveness predicts change in depressive symptoms in anxious children and adolescents following treatment. Journal of Child and Adolescent Psychopharmacology, 29(5), 378-385. https://doi.org/10.1089/cap.2018.0172
Rolls, E. T. (2019). The orbitofrontal cortex. Oxford University Press. https://doi.org/10.1093/oso/9780198845997.001.0001
Rolls, E. T. (2017). A computational neuroscience approach to understanding schizophrenia and bipolar disorder: From neuroimaging to neurodynamics. NeuroImage, 159, 388-400. https://doi.org/10.1016/j.neuroimage.2017.07.072
Van Essen, D. C. (2013). The Human Connectome Project: A data acquisition perspective. NeuroImage, 62(4), 2222-2231. https://doi.org/10.1016/j.neuroimage.2012.02.018