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Cited by 474Neural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

The orbitofrontal cortex: reward, emotion and depression

Open access
Rolls, Edmund T, Cheng, Wei, Feng, Jianfeng·2020·Brain Communications
DOI 10.1093/braincomms/fcaa196PMC PMC7749795
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Abstract

The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not obtaining an expected reward. Cortical processing before the orbitofrontal cortex is about the identity of stimuli, i.e. ‘what’ is present, and not about reward value. There is evidence that this holds for taste, visual, somatosensory and olfactory stimuli. The human medial orbitofrontal cortex represents many different types of reward, and the lateral orbitofrontal cortex represents non-reward and punishment. Not obtaining an expected reward can lead to sadness, and feeling depressed. The concept is advanced that an important brain region in depression is the orbitofrontal cortex, with depression related to over-responsiveness and over-connectedness of the non-reward-related lateral orbitofrontal cortex, and to under-responsiveness and under-connectivity of the reward-related medial orbitofrontal cortex. Evidence from large-scale voxel-level studies and supported by an activation study is described that provides support for this hypothesis. Increased functional connectivity of the lateral orbitofrontal cortex with brain areas that include the precuneus, posterior cingulate cortex and angular gyrus is found in patients with depression and is reduced towards the levels in controls when treated with medication. Decreased functional connectivity of the medial orbitofrontal cortex with medial temporal lobe areas involved in memory is found in patients with depression. Some treatments for depression may act by reducing activity or connectivity of the lateral orbitofrontal cortex. New treatments that increase the activity or connectivity of the medial orbitofrontal cortex may be useful for depression. These concepts, and that of increased activity in non-reward attractor networks, have potential for advancing our understanding and treatment of depression. The focus is on the orbitofrontal cortex in primates including humans, because of differences of operation of the orbitofrontal cortex, and indeed of reward systems, in rodents. Finally, the hypothesis is developed that the orbitofrontal cortex has a special role in emotion and decision-making in part because as a cortical area it can implement attractor networks useful in maintaining reward and emotional states online, and in decision-making.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that the primate/human orbitofrontal cortex is central to reward, non-reward, emotion, and depression, with medial OFC representing reward and lateral OFC representing non-reward/punishment. It synthesizes large-scale connectivity and activation evidence supporting a depression model of lateral OFC over-connectivity/over-responsiveness and medial OFC under-connectivity/under-responsiveness.

Key findings

  • The medial OFC (areas 13 and 11) represents reward value and subjective pleasantness, whereas the lateral OFC (area 12) represents non-reward and punishment and supports rapid rule-based reversal. Non-reward neurons were found in 18/494 (3.6%) of neurons in one study and 10/140 (7.1%) in another.
  • In 421 patients with major depressive disorder versus 488 controls, medial OFC BA 13 had reduced functional connectivity with the parahippocampal gyrus/medial temporal lobe memory system, while lateral OFC BA 47/12 had increased functional connectivity with the precuneus, angular gyrus, and temporal visual cortex BA 21; lateral OFC links were less high in medicated patients.
  • In a monetary incentive delay task with 1140 participants at age 19 and 1877 at age 14, medial OFC activation increased with reward value and lateral OFC activation increased toward No-Win; the interaction was significant at P = 10−50 at age 19 and P < 10−72 at age 14. In a subgroup with depressive symptoms, lateral OFC activation to No-Win was greater and medial OFC sensitivity to reward differences was reduced.
  • Treatments discussed include right lateral OFC rTMS, antidepressant drugs that decrease lateral OFC activity/connectivity, and potential deep brain stimulation of the medial OFC; reduced medial OFC functional connectivities were not normalized by antidepressant medication.

Methods

  • Narrative review; the paper states that no new data were created or analysed.
  • Evidence synthesized includes primate neurophysiology, lesion studies, human fMRI activation studies, resting-state functional connectivity, effective connectivity, and diffusion tractography; cited samples include 654 participants for OFC parcellation, 50 for tractography, 421 patients/488 controls, 282 patients/254 controls, 336 patients/350 controls, 1017 Human Connectome Project participants, and 1140/1877 adolescents.
  • Main analysis is qualitative integration and theory development, with emphasis on large-scale voxel-level functional connectivity to separate nearby medial and lateral OFC regions.

Limitations

  • The paper states that no new data were created or analysed; it also notes that resting-state functional connectivity for individual links is not robust with small samples, that subgenual cingulate deep brain stimulation has not been confirmed in a double-blind study, and that convergence across studies of cerebral blood flow in depression is not strong.
  • Evident from the text: this is a synthesis of separate studies rather than a single controlled experiment, and functional connectivity measures are correlational, so causal direction is not established by those measures alone.
  • Evident from the text: medication effects are described through comparisons of medicated and unmedicated patients rather than randomized treatment trials.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/braincomms/fcaa196

Cites

226 of 226 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Findingcitation

    The OFC is involved in representing the reward value of stimuli, with an emphasis on the medial and mid-OFC areas 11 and 13.

    “The evidence described above shows that the OFC is involved in representing the reward value of stimuli (with an emphasis on the medial and mid-OFC areas 11 and 13); and is involved in learning associations between stimuli and rewards, and rapidly correcting these (with an emphasis on the lateral OFC area 12 and the closely connected orbital part of the inferior frontal gyrus) (Rolls, 2018a, 2019c”
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    • cites Rolls, 2018a, 2019c

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  • Findingcitation

    OFC damage impairs emotional and social behaviour.

    “In accordance with this, the rewarding and punishing stimuli described above are all affective stimuli, and activate the OFC; and OFC damage impairs subjective emotional states (Hornak et al., 2003, Rolls, 2019c), emotional responses to stimuli such as face and voice expression (Hornak et al., 1996, 2003), and emotional and social behaviour, with the neurological evidence described in more detail”
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    • cites Rolls, 2019c, 2021b

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  • Findingcitation

    OFC damage impairs subjective emotional states.

    “In accordance with this, the rewarding and punishing stimuli described above are all affective stimuli, and activate the OFC; and OFC damage impairs subjective emotional states (Hornak et al., 2003, Rolls, 2019c), emotional responses to stimuli such as face and voice expression (Hornak et al., 1996, 2003), and emotional and social behaviour, with the neurological evidence described in more detail”
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    • cites Hornak et al., 2003 source

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    • cites Rolls, 2019c

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  • Findingcitation

    The effects of damage to the human amygdala on emotion and emotional experience are much more subtle than the effects of damage to the OFC.

    “Although the amygdala has many of the same connections as the OFC (Fig. 2), it is an evolutionarily old brain region, and appears to be overshadowed by the OFC in humans, in that the effects of damage to the human amygdala on emotion and emotional experience are much more subtle (Whalen and Phelps, 2009; Delgado et al., 2011; LeDoux and Pine, 2016; LeDoux et al., 2018) than that of damage to the”
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    • cites Whalen and Phelps, 2009

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    • cites Delgado et al., 2011 source

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    • cites LeDoux and Pine, 2016; LeDoux et al., 2018

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Findingcitation

    Neuronal responses to reinforcement predictive cues in classical conditioning update more rapidly in the macaque OFC than in the amygdala.

    “Furthermore, consistent with the poor rapid reversal learning found by amygdala neurons (Sanghera et al., 1979; Rolls, 2014) compared to OFC neurons, it has been found that neuronal responses to reinforcement predictive cues in classical conditioning update more rapidly in the macaque OFC than amygdala, and activity in the OFC but not the amygdala was modulated by recent reward history (Saez et al”
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    • cites Saez et al., 2017 source

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    Findingcitation

    The OFC is involved in learning associations between stimuli and rewards, and rapidly correcting these, with an emphasis on the lateral OFC area 12 and the closely connected orbital part of the inferior frontal gyrus.

    “The evidence described above shows that the OFC is involved in representing the reward value of stimuli (with an emphasis on the medial and mid-OFC areas 11 and 13); and is involved in learning associations between stimuli and rewards, and rapidly correcting these (with an emphasis on the lateral OFC area 12 and the closely connected orbital part of the inferior frontal gyrus) (Rolls, 2018a, 2019c”
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    • cites Rolls, 2018a, 2019c

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    Findingcitation

    Rewarding and punishing stimuli are all affective stimuli and activate the OFC.

    “In accordance with this, the rewarding and punishing stimuli described above are all affective stimuli, and activate the OFC; and OFC damage impairs subjective emotional states (Hornak et al., 2003, Rolls, 2019c), emotional responses to stimuli such as face and voice expression (Hornak et al., 1996, 2003), and emotional and social behaviour, with the neurological evidence described in more detail”
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    • cites Rolls, 2019c

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    Findingcitation

    OFC damage in humans produces profound changes in social and emotional behaviour, subjective emotional experience, and reward reversal learning.

    “However, the balance may shift towards the OFC in humans, in that it is OFC damage in humans that produces profound changes in social and emotional behaviour, and subjective emotional experience, as well as in reward reversal learning (Rolls et al., 1994; Hornak et al., 1996; 2003; Berlin et al., 2004, 2005; Hornak et al., 2004; Rolls, 2019c).”
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    • cites Rolls et al., 1994 source

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    • cites Hornak et al., 1996; 2003

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    • cites Berlin et al., 2004, 2005; Hornak et al., 2004; Rolls, 2019c

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    Findingcitation

    Activity in the OFC but not the amygdala was modulated by recent reward history.

    “Furthermore, consistent with the poor rapid reversal learning found by amygdala neurons (Sanghera et al., 1979; Rolls, 2014) compared to OFC neurons, it has been found that neuronal responses to reinforcement predictive cues in classical conditioning update more rapidly in the macaque OFC than amygdala, and activity in the OFC but not the amygdala was modulated by recent reward history (Saez et al”
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    • cites Saez et al., 2017 source

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    Findingcitation

    The lateral OFC BA 47/12 did not have this reduced functional connectivity with memory systems, so that there is an imbalance in depression towards decreased reward-related connectivity with the medial temporal lobe memory system.

    “The lateral OFC BA 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems, so that there is an imbalance in depression towards decreased reward-related connectivity with the medial temporal lobe memory system.”
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    • cites Cheng et al., 2016 source

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    Findingcitation

    Medial OFC voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus, fusiform gyrus, and supplementary motor area, and medication did not result in these functional connectivities being closer to controls.

    “In a further analysis that investigated the effects of antidepressant medication (Rolls et al., 2020a), medial OFC voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus, fusiform gyrus, and supplementary motor area, and medication did not result in these functional connectivities being closer to controls.”
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    • cites Rolls et al., 2020a

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    Findingcitation

    The subgenual (or subcallosal) cingulate cortex has been implicated in depression, and electrical stimulation in that region may relieve depression, although it has not been possible to confirm this in a double-blind study.

    “The subgenual (or subcallosal) cingulate cortex has been implicated in depression, and electrical stimulation in that region may relieve depression (Mayberg, 2003; Hamani et al., 2009, 2011; Lozano et al., 2012; Laxton et al., 2013; Lujan et al., 2013) [although it has not been possible to confirm this in a double-blind study (Holtzheimer et al., 2017)].”
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    • cites Hamani et al., 2009, 2011

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    • cites Lozano et al., 2012; Laxton et al., 2013; Lujan et al., 2013; Holtzheimer et al., 2017

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    The OFC has a special role in emotion and decision-making in part because as a cortical area it can implement attractor networks useful in maintaining reward and emotional states online, and in decision-making.

    “the hypothesis is developed that the orbitofrontal cortex has a special role in emotion and decision-making in part because as a cortical area it can implement attractor networks useful in maintaining reward and emotional states online, and in decision-making.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The lateral OFC is implicated in the effects of aversive and subjectively unpleasant stimuli, and in non-reward when a reward choice must be reversed, and has increased functional connectivity in depression.

    “the lateral OFC (area 12, Fig. 1) is implicated in the effects of aversive and subjectively unpleasant stimuli, and in not receiving expected rewards (termed ‘non-reward’) when a reward choice must be reversed and has increased functional connectivity in depression.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The striatal/basal ganglia route is used for stimulus-response habit learning, with dopamine used to provide reward prediction error in reinforcement learning.

    “The striatal/basal ganglia route is used for stimulus–response, habit, learning (Everitt and Robbins, 2013; Rolls, 2014), with dopamine used to provide reward prediction error in reinforcement learning (Schultz, 2016b; Cox and Witten, 2019).”
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    • cites Rolls, 2014

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    • cites Schultz, 2016b

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    Premisecitation

    The medial OFC is activated by rewarding and subjectively pleasant stimuli and has reduced functional connectivity in depression.

    “the medial OFC (areas 13 and 11, Fig. 1) is activated by rewarding and subjectively pleasant stimuli and has reduced functional connectivity in depression.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The OFC projects reward-related information to the ventral striatum, providing a route, in part via the habenula, for reward-related information to reach dopamine neurons, which respond to positive reward prediction error.

    “The OFC projects reward-related information to the ventral striatum (Williams et al., 1993), and this provides a route, in part via the habenula, for reward-related information to reach the dopamine neurons (Rolls, 2017), which respond inter alia to positive reward prediction error (Bromberg-Martin et al., 2010; Schultz, 2016a, 2017).”
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    • cites Williams et al., 1993 source

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    • cites Rolls, 2017 source

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    Premisecitation

    The OFC is a key brain region involved in reward value and its rapid updating in even one trial when reward value changes, and sends this information to the anterior cingulate cortex for actions to be learned guided by reward or non-reward outcomes.

    “the orbitofrontal is a key brain region involved in reward value and its rapid updating in even one trial when the reward value changes, and sends this information to the anterior cingulate cortex for actions to be learned guided by the reward or non-reward outcomes received (Rolls, 2019b).”
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    • cites Rolls, 2019b

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    Premisecitation

    The anterior cingulate cortex receives information about reward outcomes from the OFC, and the posterior cingulate cortex receives information from the parietal cortex about actions just performed, providing signals needed for action-outcome goal-related learning, and sends outputs to premotor areas from the mid-cingulate cortex.

    “the anterior cingulate cortex can be conceptualized as receiving information about reward outcomes from the OFC, and the posterior cingulate cortex as receiving information from the parietal cortex about actions just performed, providing the signals needed for action–outcome goal-related learning, and sending outputs to premotor areas from the mid-cingulate cortex (Rolls, 2019b).”
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    • cites Rolls, 2019b

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    Premisecitation

    Outputs of the OFC reach the anterior cingulate cortex, striatum, insula and inferior frontal gyrus, and enable reward value representations in the OFC to influence behaviour.

    “Outputs of the OFC reach the anterior cingulate cortex (Rolls, 2019c), the striatum, the insula and the inferior frontal gyrus, and enable the reward value representations in the OFC to influence behaviour (Fig. 2, green).”
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    • cites Rolls, 2019c

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    Premisecitation

    Economic value is represented in the OFC, with single neurons reflecting the trade-off between the quality of a reward and the amount available.

    “Economic value is represented in the OFC, in that, for example, single neurons reflect the trade-off between the quality of a reward and the amount that is available (Padoa-Schioppa and Conen, 2017).”
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    Premisecitation

    The lateral OFC and right inferior frontal gyrus also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the lateral OFC and right inferior frontal gyrus.

    “The lateral OFC and right inferior frontal gyrus also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the lateral OFC and right inferior frontal gyrus.”
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    • cites Hsu et al., 2020 source

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    Premisecitation

    In humans, the medial OFC is activated by many rewarding stimuli and reflects their subjective pleasantness.

    “In humans, the medial OFC is activated by many rewarding stimuli and reflects their subjective pleasantness (Grabenhorst and Rolls, 2011; Rolls, 2019c).”
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    Premisecitation

    The macaque OFC contains neurons that reflect face expression and face identity, social categories such as young faces, and position in the social hierarchy.

    “The macaque OFC contains neurons that reflect face expression and face identity (both necessary to decode value and important in social behaviour) (Thorpe et al., 1983; Rolls et al., 2006), and also social categories such as young faces (Barat et al., 2018) and position in the social hierarchy (Munuera et al., 2018).”
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    Premisecitation

    Some OFC neurons respond to outcome value, and others to expected value; humans with ADHD have increased sensitivity to future rewards.

    “These investigations show that some OFC neurons respond to outcome value (e.g. the taste of food), and others to expected value (or future rewards), and interestingly humans with ADHD have increased sensitivity to these future rewards (Tegelbeckers et al., 2018).”
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    Premisecitation

    The OFC outputs to the insula include a projection to the viscero-autonomic cortex in the antero-ventral insula that helps account for why the insula is activated in some tasks in which the OFC is involved.

    “The OFC outputs to the insula include a projection to the viscero-autonomic cortex in the antero-ventral insula (Hassanpour et al., 2018) that helps to account for the reason why the insula is activated in some tasks in which the OFC is involved (Rolls, 2016c, 2019c).”
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    • cites Rolls, 2016c

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    Interpretationcitation

    This rapid reversal is rule-based, requiring a rule held in memory and reversed by non-reward.

    “This capability requires a rule to be held in memory and reversed by non-reward (Deco and Rolls, 2004; Rolls and Deco, 2016)”
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    Premisecitation

    The lateral OFC projects to the inferior frontal gyrus, to a region on the right implicated in stopping behaviour, and to a region on the left that includes Broca's area.

    “The lateral OFC also projects to the inferior frontal gyrus (Hsu et al., 2020; Du et al., 2020a), to a region that on the right is implicated in stopping behaviour (Aron et al., 2014), and to a region on the left that includes Broca’s area (Hsu et al., 2020; Rolls, 2021a).”
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    Premisecitation

    This medial OFC activation by rewarding stimuli is found for odours, flavour, pleasant touch, monetary reward and amphetamine.

    “This is found for odours (Rolls et al., 2003a), flavour (de Araujo et al., 2003; Kringelbach et al., 2003), pleasant touch (Rolls et al., 2003b; McCabe et al., 2008), monetary reward (O’Doherty et al., 2001; Xie et al., 2020) and amphetamine (Völlm et al., 2004).”
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    • cites Rolls et al., 2003a

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    • cites Kringelbach et al., 2003

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    Premisecitation

    The human lateral OFC is activated when a reward is not obtained in a visual discrimination reversal task, when money is not received in a monetary reward task, and in a one-trial rule-based reward reversal task.

    “the human lateral OFC is activated when a reward is not obtained in a visual discrimination reversal task (Kringelbach and Rolls, 2003) (Fig. 4A), and when money is not received in a monetary reward task (O’Doherty et al., 2001; Xie et al., 2020), and in a one-trial rule-based reward reversal task (Rolls et al., 2020b).”
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    Interpretationcitation

    These non-reward neurons can be described as negative reward prediction error neurons, responding when a reward outcome is less than expected.

    “They can be described as negative reward prediction error neurons, in that they respond when a reward outcome is less than was expected (Rolls, 2019c).”
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    • cites Rolls, 2019c

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    Premisereasoning

    OFC damage produces problems in decision-making, including failing to respond correctly to non-reward.

    “This is supported by the problems that OFC damage produces in decision-making, which include failing to respond correctly to non-reward, as described next.”
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    Interpretationcitation

    Non-reward neurons are computed in the OFC because it is the first brain region in primates at which expected value and outcome value are represented, and these two signals are required to compute non-reward.

    “The hypothesis is that these non-reward neurons are computed in the OFC, because this is the first brain region in primates at which expected value and outcome value are represented, and these two signals are those required to compute non-reward, that is, reward outcome < expected value (as shown in Fig. 2) and with the evidence set out fully by Rolls (2019c, 2021a).”
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    • cites Rolls, 2019c

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    Premisecitation

    Lesions of the OFC can impair behavioural changes to non-reward; in humans, reward reversal learning is impaired, with continued responding to the previously rewarded, now non-rewarded, stimulus.

    “Consistent with this neurophysiological and neuroimaging evidence, lesions of the OFC can impair behavioural changes to non-reward. For example, reward reversal learning is impaired during decision-making in humans, who continue responding to the previously rewarded, now non-rewarded, stimulus (Rolls et al., 1994; Hornak et al., 2004; Fellows, 2011).”
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    Premisecitation

    The finding of non-reward neurons is robust: 18/494 (3.6%) of neurons in the original study responded to non-reward, 10/140 (7.1%) in a complementary study, and an fMRI study showed macaque lateral OFC activation when expected reward was not obtained during reversal.

    “The finding of non-reward neurons is robust, in that 18/494 (3.6%) of the neurons in the original study responded to non-reward (Thorpe et al., 1983), consistent results were found in different tasks in a complementary study (10/140 non-reward neurons in the OFC or 7.1%) (Rosenkilde et al., 1981), and an fMRI study has shown that the macaque lateral OFC is activated when an expected reward is not”
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    Premisecitation

    In a study with 1877 participants, the medial OFC is activated by reward (winning money or candies) and the lateral OFC is activated by not winning.

    “A recent study with 1877 participants emphasizes these points, by showing that the medial OFC is activated by reward (such as winning money or candies) and that the lateral OFC is activated by not winning (Fig. 5) (Xie et al., 2020).”
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    Premisecitation

    Humans with OFC lesions may be less sensitive to reward, as shown by reduced subjective emotional feelings, altered social and emotional behaviour, and problems with face and voice expression processing.

    “Humans with OFC lesions may also be less sensitive to reward, as shown by their reduced subjective emotional feelings and altered social and emotional behaviour and problems with face and voice expression processing (Rolls et al., 1994; Hornak et al., 1996, 2003; Rolls, 2021b).”
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    Interpretationcitation

    The role of the OFC in emotion is to decode the reward/punishment goals for action, by representing reward value, and by learning about stimuli with reward versus non-reward contingencies, and then to transmit the resulting representations to further brain regions (such as the cingulate cortex) which implement the learning of actions to obtain the reward outcomes signalled by the OFC.

    “In this context, the theory of emotion holds that the role of the OFC in emotion is to decode the reward/punishment goals for action, by representing reward value, and by learning about stimuli with reward versus non-reward contingencies, and then to transmit the resulting representations to further brain regions (such as the cingulate cortex) which implement the learning of actions to obtain the”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rolls, 2019a,b

      Not checked in the free run.

    • cites Rolls, 2021a

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The attractor model of decision-making is a neuronal network with associatively modifiable recurrent collateral synapses between neurons of the type prototypical of the cerebral cortex.

    “The attractor model of decision-making is a neuronal network with associatively modifiable recurrent collateral synapses between the neurons of the type prototypical of the cerebral cortex (Wang, 2002; Rolls and Deco, 2010; Rolls, 2021a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wang, 2002 source

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    • cites Rolls and Deco, 2010

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    • cites Rolls, 2021a

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  • May combine two claims.

    Premisecitation

    The VMPFC has the signature of a decision-making region of increasing its activation in proportion to the difference in the decision variables, which correlates with decision confidence.

    “it has the signature of a decision-making region of increasing its activation in proportion to the difference in the decision variables, which correlates with decision confidence (Rolls et al., 2010a,b; Rolls, 2019c).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Rolls et al., 2010a

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    • cites Rolls et al., 2010b

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    • cites Rolls, 2019c

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  • May combine two claims.

    Premisecitation

    Single neurons in the macaque VMPFC signal the value of the chosen offer, suggesting that the network produces a choice.

    “single neurons in the macaque ventromedial prefrontal cortex signal the value of the chosen offer, suggesting that the network produces a choice (Strait et al., 2014), also consistent with the attractor model of decision-making (Rolls et al., 2010a,b; Rolls, 2014, 2016b, 2021a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Strait et al., 2014 source

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    • cites Rolls et al., 2010a

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    • cites Rolls et al., 2010b

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  • May combine two claims.

    Premisecitation

    The decision variables are applied simultaneously, and the network, after previous training with these decision variables, reaches a state where the population of neurons representing one of the decision variables has a high firing rate.

    “The decision variables are applied simultaneously, and the network, after previous training with these decision variables, reaches a state where the population of neurons representing one of the decision variables has a high firing rate (Rolls and Deco, 2010; Deco et al., 2013; Rolls, 2016b; 2021a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Rolls and Deco, 2010

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    • cites Deco et al., 2013 source

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    • cites Rolls, 2016b; 2021a

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  • May combine two claims.

    Premisecitation

    Some studies of macaque OFC lesions have been incomplete, including only medial areas 13 and 11 and not lateral area 12, and one such study reported no reversal learning deficit and suggested OFC was not involved in reversal.

    “It has been a problem in some studies of the orbitofrontal cortex in macaques that the OFC lesions have been incomplete, with for, example, the lesions including only the medial areas 13 and 11, and not the lateral OFC area 12, with one study reporting no reversal learning deficit after such a medial lesion, and suggesting that the OFC was not involved in reversal (Rudebeck et al., 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rudebeck et al., 2013 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This type of flexibility of behaviour is important in primate including human social interactions.

    “This type of flexibility of behaviour is important in primate including human social interactions (Rolls, 2018a, 2019c).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rolls, 2018a

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    • cites Rolls, 2019c

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  • May combine two claims.

    Premisecitation

    The VMPFC includes the gyrus rectus area 14 and parts of 10m and 10r, receives inputs from the OFC, and has distinct connectivity with the superior medial prefrontal cortex, cingulate cortex and angular gyrus.

    “The ventromedial prefrontal cortex (VMPFC, which can be taken to include the gyrus rectus area 14 and parts of 10m and 10r, Fig. 1) receives inputs from the OFC and has distinct connectivity [with strong functional connectivity with the superior medial prefrontal cortex, cingulate cortex and angular gyrus (Du et al., 2020a)].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Du et al., 2020a

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  • May combine two claims.

    Premisecitation

    The rodent OFC and the whole operation of reward systems in rodents appear to be somewhat different from that in primates including humans.

    “The reason for this focus is that the rodent OFC (Schoenbaum et al., 2009; Wilson et al., 2014; Sharpe et al., 2015; Izquierdo, 2017; Sharpe et al., 2019), and the whole operation of reward systems in rodents, appears to be somewhat different from that in primates including humans (Rolls, 2019c, 2021a), as follows.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2019c, 2021a

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  • May combine two claims.

    Premisecitation

    The rodent OFC contains only agranular cortex, which corresponds to only a small region of the primate OFC, posteriorly.

    “First, the rodent OFC contains only agranular cortex, which corresponds to only a small region of the primate OFC, posteriorly (Wise, 2008; Passingham and Wise, 2012; Passingham, 2021), and these authors provide evidence that there is no equivalent in rodents of most of the primate OFC.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Wise, 2008 source

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    • cites Passingham and Wise, 2012

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    • cites Passingham, 2021 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    In the passive condition, non-reward may produce depression.

    “In the passive condition, non-reward may produce depression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In rodents, reward value as indicated in devaluation (satiety) studies involves reward processing even far peripherally in the first central relay, the nucleus of the solitary tract for taste, and the olfactory bulb for odour.

    “Third, in rodents, reward value as indicated in devaluation (satiety) studies involves reward processing even far peripherally in the first central relay, the nucleus of the solitary tract for taste (Giza and Scott, 1983, 1987; Giza et al., 1992), and the olfactory bulb for odour (Pager et al., 1972), making these complex systems, as reward and identity processing about taste and odour are”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Giza and Scott, 1983, 1987

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    • cites Giza et al., 1992 source

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    • cites Pager et al., 1972 source

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  • May combine two claims.

    Premisecitation

    The primate OFC specializes in reward (and punishment and non-reward) value representations, but not in interfacing these value representations to actions or to responses.

    “The primate OFC, in contrast, appears to specialize in reward (and of course punishment and non-reward) value representations, but not in interfacing these value representations to actions [which occurs in the primate cingulate cortex (Rolls, 2019b2021a)] or to responses (which occurs in the striatum and other parts of the basal ganglia), for actions and responses are poorly if at all represented”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Thorpe et al., 1983 source

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    • cites Padoa-Schioppa and Assad, 2006 source

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    • cites Grattan and Glimcher, 2014; Rolls, 2019c

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  • May combine two claims.

    Premisecitation

    In the mouse, neurons in LO represent the values of individual options, the binary choice outcome and the chosen value, in the context of spatial responses, not of the value of goods as in primates.

    “Although it is interesting that in the mouse, neurons in LO represent the values of individual options, the binary choice outcome and the chosen value, this is in the context of spatial responses (Kuwabara et al., 2020), not of the value of goods as in primates.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kuwabara et al., 2020 source

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  • May combine two claims.

    Premisecitation

    In the rodent (agranular) OFC, both reward value and behavioural responses are represented, making the rodent OFC very different from the primate OFC.

    “Fourth, although reward value is represented in the rodent (agranular) OFC, so also apparently are behavioural responses (Schoenbaum et al., 2009; Wilson et al., 2014; Sharpe et al., 2015, 2019; Izquierdo, 2017), which makes the rodent OFC very different to the primate OFC.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Schoenbaum et al., 2009 source

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    • cites Wilson et al., 2014 source

      Not checked in the free run.

    • cites Sharpe et al., 2015, 2019; Izquierdo, 2017

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    The effects of non-reward can be prolonged by rumination of sad thoughts, which is supported by a long loop attractor involving language areas in the angular gyrus and related regions, which receive inputs from the lateral OFC, and project back to it.

    “It is postulated that the effects of the non-reward can be prolonged by rumination of sad thoughts which is supported by a long loop attractor involving language areas in the angular gyrus and related regions, which receive inputs from the lateral OFC, and project back to it.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    This type of rapid, rule-based, reversal provides a foundation for rapid changes in social behaviour whenever feedback is received, and a similar rule-based system is not known to be present in rodents.

    “This type of rapid, rule-based, reversal provides a foundation for rapid changes in social behaviour whenever feedback is received, and a similar rule-based system is not known to be present in rodents.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Neurons in the rodent lateral OFC respond in reward reversal and silencing these neurons impairs the reversal.

    “However, it is of interest that neurons in the rodent lateral OFC respond in reward reversal and that silencing these neurons impairs the reversal (Banerjee et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Banerjee et al., 2020 source

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  • May combine two claims.

    Premisecitation

    The cortex provides a computational basis in its attractor networks for holding information online, and therefore producing behaviour that depends on 'hidden' internal states, rather than being more dominated by sensory input.

    “This is consistent with the great development of cortical processing for these functions provided by the primate OFC, given that the cortex provides a computational basis in its attractor networks for holding information online, and therefore producing behaviour that depends on ‘hidden’ internal states, rather than being more dominated by sensory input (Rolls, 2016b, 2021a).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2016b, 2021a

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The retrosplenial cortex provides connections and receives connections from the hippocampal system, connecting especially with the parahippocampal gyrus areas TF and TH, and with the subiculum.

    “The retrosplenial cortex provides connections and receives connections from the hippocampal system, connecting especially with the parahippocampal gyrus areas TF and TH, and with the subiculum (Kobayashi and Amaral, 2003, 2007; Bubb et al., 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kobayashi and Amaral, 2003, 2007

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    • cites Bubb et al., 2017 source

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  • May combine two claims.

    Interpretationcitation

    The non-reward system in the lateral OFC has increased effects on areas in which the self is represented including the precuneus, which could relate to the low self-esteem in depressed patients.

    “These findings support the theory that the non-reward system in the lateral OFC has increased effects on areas in which the self is represented including the precuneus, which could relate to the low self-esteem in depressed patients (Rolls, 2016a).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2016a

      Not checked in the free run.

    • Rests on an assumption: Functional connectivity differences between brain regions reflect differences in communication between those regions.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The precuneus is a medial parietal cortex region implicated in the sense of self and agency, autobiographical memory, spatial function, and navigation.

    “The precuneus is a medial parietal cortex region implicated in the sense of self and agency, autobiographical memory, spatial function. and navigation (Cavanna and Trimble, 2006; Freton et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cavanna and Trimble, 2006 source

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    • cites Freton et al., 2014 source

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  • May combine two claims.

    Interpretationcitation

    The subgenual/subcallosal anterior cingulate cortex receives inputs from the OFC, and this helps understand its implication in depression.

    “This approach based on advances in understanding the functions of the primate including human OFC also provides an approach to understanding how other brain systems such as the subgenual/subcallosal anterior cingulate cortex are implicated in depression (Mayberg et al., 2016), in that they receive inputs from the OFC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mayberg et al., 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The precuneus provides access to the hippocampus for spatial information from the parietal cortex.

    “The precuneus provides access to the hippocampus for spatial information from the parietal cortex (given the rich connections between the precuneus and the parietal cortex) (Rolls and Wirth, 2018; Rolls, 2021a).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Rolls and Wirth, 2018

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    • cites Rolls, 2021a

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The posterior cingulate region (including the retrosplenial cortex) is consistently engaged by a range of tasks that examine episodic memory including autobiographical memory, and imagining the future; and also spatial navigation and scene processing.

    “The posterior cingulate region (including the retrosplenial cortex) is consistently engaged by a range of tasks that examine episodic memory including autobiographical memory, and imagining the future; and also spatial navigation and scene processing (Auger and Maguire, 2013; Leech and Sharp, 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Auger and Maguire, 2013

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    • cites Leech and Sharp, 2014 source

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  • May combine two claims.

    Premisecitation

    The supracallosal anterior cingulate cortex is activated by many aversive stimuli, and has strong connectivity with the lateral OFC and adjoining part of the inferior frontal gyrus.

    “The supracallosal anterior cingulate cortex is activated by many aversive stimuli (Grabenhorst and Rolls, 2011, Rolls, 2014, 2019b), and has strong connectivity with the lateral OFC and adjoining part of the inferior frontal gyrus (Rolls et al., 2019; Hsu et al., 2020; Du et al., 2020a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Grabenhorst and Rolls, 2011 source

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    • cites Rolls, 2014, 2019b

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    • cites Rolls et al., 2019; Hsu et al., 2020; Du et al., 2020a

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  • May combine two claims.

    Interpretationcitation

    The anhedonia of depression and reduced happy memories are related to these low functional connectivities of the medial OFC with temporal lobe and memory systems.

    “This is consistent with the anhedonia of depression and reduced happy memories being related to these low functional connectivities of the medial OFC with temporal lobe and memory systems.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls et al., 2020a

      Not checked in the free run.

    • Rests on an assumption: Functional connectivity differences between brain regions reflect differences in communication between those regions.

  • May combine two claims.

    Premisecitation

    The posterior cingulate cortex also has connections with the OFC, and has high functional connectivity with the parahippocampal regions that are involved in memory.

    “The posterior cingulate cortex also has connections with the OFC (Vogt and Pandya, 1987; Vogt and Laureys, 2009), and the posterior cingulate cortex has high functional connectivity with the parahippocampal regions that are involved in memory (Cheng et al., 2018b; Rolls, 2019b).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Vogt and Pandya, 1987

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    • cites Vogt and Laureys, 2009

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    • cites Cheng et al., 2018b; Rolls, 2019b

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  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    These low functional connectivities are not normalized by treatment with antidepressant drugs, suggesting that one goal of future treatment for depression might be to increase the functionality of the medial OFC.

    “What is especially interesting is that these low functional connectivities are not normalized by treatment with antidepressant drugs (Rolls et al., 2020a), suggesting that one goal of future treatment for depression might be to increase the functionality of the medial OFC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls et al., 2020a

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The posterior cingulate cortex is a region with strong connectivity in primates with the entorhinal cortex and parahippocampal gyrus (areas TF and TH), and thus with the hippocampal memory system.

    “The posterior cingulate cortex is a region with strong connectivity in primates with the entorhinal cortex and parahippocampal gyrus (areas TF and TH), and thus with the hippocampal memory system (Vogt, 2009; Bubb et al., 2017; Rolls and Wirth, 2018; Rolls, 2018b; 2019b,c, 2021a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Vogt, 2009

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    • cites Bubb et al., 2017 source

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    • cites Rolls and Wirth, 2018; Rolls, 2018b; 2019b,c, 2021a

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  • Probably not a substantial claim: may not pass S1 (asserted).

    Interpretationcitation

    One way in which the orbitofrontal cortex influences behaviour in depression is via the right inferior frontal gyrus, which projects to premotor cortical areas.

    “The hypothesis was proposed that one way in which the OFC influences behaviour in depression is via the right inferior frontal gyrus, which projects in turn to premotor cortical areas (Du et al., 2020a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Du et al., 2020a

      Not checked in the free run.

    • Rests on an assumption: The lateral orbitofrontal cortex projects to the inferior frontal gyrus.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The inferior frontal gyrus route may allow non-reward signals to have too great an effect to inhibit behaviour in depression.

    “Consistent with the consequent hypothesis that the inferior frontal gyrus route may allow non-reward signals to have a too great effect to inhibit behaviour in depression”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The pregenual cingulate cortex is activated by many pleasant, rewarding, stimuli, and has strong functional connectivity with the medial OFC.

    “The pregenual cingulate cortex is activated by many pleasant, rewarding, stimuli (Grabenhorst and Rolls, 2011; Rolls, 2014, 2019b), and has strong functional connectivity with the medial OFC (Rolls et al., 2019; Hsu et al., 2020; Du et al., 2020a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Grabenhorst and Rolls, 2011 source

      Not checked in the free run.

    • cites Rolls, 2014, 2019b

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    • cites Rolls et al., 2019; Hsu et al., 2020; Du et al., 2020a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Electrical stimulation of the subcallosal region, which includes parts of the ventromedial prefrontal cortex, that may relieve depression, may do so at least in part by activating connections involving the OFC, other parts of the anterior cingulate cortex, and the striatum.

    “Furthermore, the possibility is considered that electrical stimulation of the subcallosal region, which includes parts of the ventromedial prefrontal cortex (Laxton et al., 2013), that may relieve depression, may do so at least in part by activating connections involving the OFC, other parts of the anterior cingulate cortex, and the striatum (Johansen-Berg et al., 2008; Hamani et al., 2009; Lujan”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Laxton et al., 2013 source

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    • cites Johansen-Berg et al., 2008 source

      Not checked in the free run.

    • cites Hamani et al., 2009; Lujan et al., 2013

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The medial OFC is involved in reward-related processing and learning, and the lateral OFC in non-reward and punishment-related processing and learning.

    “In contrast, the medial OFC is involved in reward-related processing and learning, and the lateral OFC in non-reward and punishment-related processing and learning (Rolls, 2019c).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2019c

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The subgenual cingulate cortex is also implicated in autonomic function, and this could be related to some of the effects found in this area that are related to depression.

    “However, the subgenual cingulate cortex is also implicated in autonomic function (Gabbott et al., 2003), and this could be related to some of the effects found in this area that are related to depression.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gabbott et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The amygdala is involved in emotion, though it may be overshadowed in humans by the orbitofrontal cortex.

    “The amygdala is involved in emotion, though as shown above it may be overshadowed in humans by the OFC (LeDoux and Pine, 2016; Rolls, 2019c).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites LeDoux and Pine, 2016 source

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    • cites Rolls, 2019c

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lesions of the right inferior frontal gyrus impair stopping in the stop-signal task and produce impulsiveness.

    “lesions of the right inferior frontal gyrus impair stopping in the stop-signal task, and produce impulsiveness (Aron et al., 2004, 2014).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Aron et al., 2004 source

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    • cites Aron et al., 2014 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sleep is frequently impaired in depression.

    “Sleep is frequently impaired in depression (Becker et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Becker et al., 2017 source

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  • May combine two claims.

    Interpretationreasoning

    This implies less strong positive driving influences of these input regions on the medial and middle orbitofrontal cortex, regions implicated in reward, and helps to elucidate part of the decreased feelings of happy states in depression.

    “This implies less strong positive driving influences of these input regions on the medial and middle OFC, regions implicated in reward, and thus helps to elucidate part of the decreased feelings of happy states in depression (Rolls, 2016a).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2016a

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low sleep duration and depression are related to structural differences of the orbitofrontal cortex.

    “Low sleep duration and depression are also related to structural differences of the OFC (Cheng et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cheng et al., 2020 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    This may relate to representations of the sense of self, which become more negative in depression.

    “this may relate to representations of the sense of self (Cavanna and Trimble, 2006), which become more negative in depression (Cheng et al., 2016; Rolls, 2016a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cavanna and Trimble, 2006 source

      Not checked in the free run.

    • cites Cheng et al., 2016 source

      Not checked in the free run.

    • cites Rolls, 2016a

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Factors associated with these differences are low maternal age, problems in the family, severe nausea and vomiting in pregnancy, and low sleep duration.

    “The factors that are associated with these differences are low maternal age (Du et al., 2020b), problems in the family (Gong et al., 2020), severe nausea and vomiting in pregnancy (Wang et al., 2020) and low sleep duration (Cheng et al., 2020).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Du et al., 2020b

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    • cites Gong et al., 2020

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    • cites Wang et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Positive reward prediction error in the medial orbitofrontal cortex is reduced in depression, correlated with anhedonia, but learning was intact, in 28 drug-naive patients with depression.

    “it was found that positive reward prediction error in the medial OFC is reduced in depression, and was correlated with anhedonia, but the learning was intact, in 28 drug-naive patients with depression (Rothkirch et al., 2017).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rothkirch et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These new findings provide support for the hypothesis that those with symptoms of depression have increased sensitivity to non-reward in the lateral orbitofrontal cortex, and decreased sensitivity for differences in reward of the medial orbitofrontal cortex.

    “These new findings provide support for the hypothesis that those with symptoms of depression have increased sensitivity to non-reward in the lateral OFC, and decreased sensitivity for differences in reward of the medial OFC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xie et al., 2020

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There is some evidence for altered structure and function of the lateral orbitofrontal cortex in depression.

    “For completeness, we note that there is some evidence for altered structure and function of the lateral OFC in depression (Drevets, 2007; Price and Drevets, 2012; Ma, 2015).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Drevets, 2007 source

      Not checked in the free run.

    • cites Price and Drevets, 2012 source

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    • cites Ma, 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Their study was consistent with evidence that reward sensitivity and not learning rates are reduced in anhedonic depression.

    “Their study was consistent with evidence that reward sensitivity and not learning rates are reduced in anhedonic depression (Huys et al., 2013; Chen et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Huys et al., 2013 source

      Not checked in the free run.

    • cites Chen et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reductions of grey-matter volume have been demonstrated specifically in the posterolateral orbitofrontal cortex (BA 47, caudal BA 11 and adjoining BA 45), and also in the subgenual cingulate cortex (BA 24, 25).

    “reductions of grey-matter volume have been demonstrated specifically in the posterolateral OFC (BA 47, caudal BA 11 and the adjoining BA 45), and also in the subgenual cingulate cortex (BA 24, 25) (Nugent et al., 2006; Drevets, 2007; Grieve et al., 2013).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Nugent et al., 2006 source

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    • cites Drevets, 2007 source

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    • cites Grieve et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Depression relates to effects produced by increased non-reward or non-reward sensitivity, or decreased reward or reward sensitivity.

    “The general approach to depression described here, that it relates to effects produced by increased non-reward or non-reward sensitivity, or decreased reward or reward sensitivity (Fig. 6), has implications for self-help and behavioural treatments for depression (Rolls, 2018a), as well as for medical interventions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2018a

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Electrical stimulation of the human orbitofrontal cortex can produce reward and raise mood.

    “Electrical stimulation of the human OFC can also produce reward and raise mood (Rao et al., 2018)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rao et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many of the sites were in the middle part of the orbitofrontal cortex, areas 13 and 11, which are categorized as medial orbitofrontal cortex, the area activated by rewards.

    “many of the sites were in the middle part of the OFC, areas 13 and 11, which are categorized as medial OFC, the area activated by rewards (Rolls, 2019c).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rao et al., 2018 source

      Not checked in the free run.

    • cites Rolls, 2019c

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Subcallosal cingulate stimulation affects pathways that connect with the orbitofrontal cortex.

    “it is possible that the subcallosal cingulate stimulation affects pathways that connect with the OFC (Johansen-Berg et al., 2008; Lujan et al., 2013; Dunlop et al., 2017; Riva-Posse et al., 2018).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Johansen-Berg et al., 2008 source

      Not checked in the free run.

    • cites Lujan et al., 2013 source

      Not checked in the free run.

    • cites Dunlop et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These increases appear related to mood change, becoming more normal when the mood state remits.

    “these increases appear to be related to the mood change, in that they become more normal when the mood state remits (Drevets, 2007)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Drevets, 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Short-term memory is potentially useful for holding mood online for some time.

    “Short-term memory is also potentially very useful for holding mood online for some time”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    This separation allows the value of many stimuli in the high dimensional space of different rewards to be represented, and competition between them to be useful for computing relative reward value.

    “This separation allows the value of many stimuli in the high dimensional space of different rewards (Rolls, 2014) to be represented, and for competition between them to be useful for computing relative reward value (Grabenhorst and Rolls, 2009).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rolls, 2014

      Not checked in the free run.

    • cites Grabenhorst and Rolls, 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The rodent orbitofrontal cortex is involved in motor responses and actions, so it can be less specialized for representing reward value and rapidly changing it.

    “the rodent ‘OFC’ is also involved in motor responses and actions (Wilson et al., 2014), so it can be less specialized for representing reward value, and rapidly changing it.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wilson et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The primate and human orbitofrontal cortex receives inputs from representations of what stimulus is present from every sensory modality at the top of each sensory cortical hierarchy, independently of reward value, and computes multimodal representations that are represented in terms of their reward value.

    “the primate and human OFC as a neocortical area is beautifully connected anatomically to receive inputs from representations of ‘what’ stimulus is present from every sensory modality at the top of each sensory cortical hierarchy, independently of reward value (Fig. 2), and then to compute multimodal representations that are then represented in terms of their reward value.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rolls, 2019c

      Not checked in the free run.

    • cites Rolls, 2021a

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The primate including human orbitofrontal cortex is a key brain region in reward value representation and in emotion.

    “The research described here provides evidence that the primate including human OFC is a key brain region in reward value representation and in emotion (Rolls, 2019c).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls, 2019c

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The primate orbitofrontal cortex represents values, but not actions.

    “The primate OFC represents values, but not actions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The primate orbitofrontal cortex projects reward value representations to the pregenual anterior cingulate cortex and punishment value representations to the supracallosal anterior cingulate cortex.

    “the primate OFC projects reward value representations to the pregenual anterior cingulate cortex, and punishment value representations to the supracallosal anterior cingulate cortex (Hsu et al., 2020; Du et al., 2020a)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Hsu et al., 2020 source

      Not checked in the free run.

    • cites Du et al., 2020a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    The subgenual cingulate cortex is involved in depression, for it receives major inputs from the orbitofrontal cortex.

    “these new approaches relate to ideas that the subgenual cingulate cortex is involved in depression, for it receives major inputs from the OFC.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Imaging in approximately the plane of the Sylvian fissure enables imaging of both the orbitofrontal cortex and the medial temporal lobe.

    “we have successfully used imaging in approximately the plane of the Sylvian fissure, which enables imaging of both the OFC and the medial temporal lobe, as set out in the previously published articles (Deichmann et al., 2002, 2003; Rolls et al., 2015b, 2020b).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Deichmann et al., 2002 source

      Not checked in the free run.

    • cites Deichmann et al., 2003 source

      Not checked in the free run.

    • cites Rolls et al., 2015b

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The orbitofrontal cortex is a difficult brain region for fMRI because signal dropout and distortion can occur due to inhomogeneities in the magnetic field produced by the air-filled bony sinuses.

    “The orbitofrontal cortex is a difficult brain region for fMRI as sometimes signal dropout and distortion can occur due to inhomogeneities in the magnetic field being produced by the air-filled bony sinuses.”
    Quote in the paperNot a substantial claim
95 of 95

  • The paper relies on this without support.

    Not obtaining an expected reward can lead to sadness and feeling depressed.

    “Not obtaining an expected reward can lead to sadness, and feeling depressed.”

  • The paper relies on this without support.

    Functional connectivity differences between brain regions reflect differences in communication between those regions.

    “There is considerable interest in functional connectivity differences between people with major depressive disorder and controls, for increased functional connectivity could reflect increased communication between brain regions, and decreased connectivity the opposite.”

  • The paper relies on this without support.

    The lateral orbitofrontal cortex projects to the inferior frontal gyrus.

    “The lateral OFC projects to the inferior frontal gyrus, and, very interestingly, higher functional connectivity was found in depression of voxels in the right inferior frontal gyrus”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The orbitofrontal cortex participates in coding the rewarding properties of sensory stimuli and is part of the mesocortical dopamine pathway.

    “the orbitofrontal cortex is reported to participate in coding the rewarding properties of sensory stimuli, being part of the mesocortical dopamine pathway [64].”

    From Positive early-life olfactory memory is rooted in the olfactory bulb and triggers large-scale changes beyond the olfactory system (2026) · cites this paper as [64]

    The sections on reward value and OFC connections describe the orbitofrontal cortex as representing the reward value of sensory stimuli. The connections section describes a route by which OFC information reaches dopamine neurons, but does not identify the OFC as part of the mesocortical dopamine pathway. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Medial OFC-supracallosal cingulate connectivity is reported in opposite directions

    Major

    The Figure 8 caption lists this connection as lower in depression, while the results text says it is increased.

  • Figure 4 assigns panel B to two different tasks

    Minor

    The caption identifies panel B both as a reversal-trial activation image and as an image of activations during a stop-signal task.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Rolls, 2012, On the implications of brain science
  2. Rolls, 2018, The brain, emotion, and depression
  3. Rolls, 2021, Handbook of clinical neurology: emotional disorders associated with neurological diseases
  4. Vogt, 2019, Handbook of clinical neurology: cingulate cortex

Cited by

Sorted by citations

Related

Authors
Rolls, E. T., Cheng, W., & Feng, J.
Affiliations
Fudan University (CN)
Corresponding author
Feng, Jianfeng
ORCID
Venue
Brain Communications
Publisher
Oxford University Press (OUP)
Published
2020
Volume
2
Issue
2
Pages
fcaa196-fcaa196
ISSN
2632-1297 (ISSN-L)
DOI
10.1093/braincomms/fcaa196
PMC
PMC7749795
OpenAlex
W3101254306
Semantic Scholar
4767ee671ac12d2b374b98703d981233ae6e27ad
Cited by
474
References
226
Citations by year
2026: 107 · 2025: 113 · 2024: 92 · 2023: 69 · 2022: 60 · 2021: 32 · 2020: 1
FWCI
5.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
Funders
  • National Key R&D Program of China (2019YFA0709502, 2018YFC1312904)
  • Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)
  • National Natural Sciences Foundation of China (82071997, 81701773)
  • Natural Science Foundation of Shanghai (18ZR1404400)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
orbitofrontal cortex, depression, reward value, punishment, medial orbitofrontal cortex, lateral orbitofrontal cortex, functional connectivity, attractor networks, emotions, decision-making, antidepressant treatment, medial temporal lobe, precuneus, posterior cingulate cortex, angular gyrus, primate neuroscience

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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