CoChat
Sign Up
Cited by 1,036Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeural dynamics and brain function

Dopamine reward prediction-error signalling: A two-component response

Open access
Schultz, Wolfram·2016·Nature Reviews Neuroscience
DOI 10.1038/nrn.2015.26PMC PMC5549862
Open this paper in CoChat — free account

Abstract

Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy.

AI snapshot

Written from the paper’s full text.

TL;DR

Schultz proposes that the phasic dopamine reward prediction-error response has two sequential components: an initial brief, unselective, highly sensitive detection response to many unpredicted stimuli, followed by a main response that codes subjective reward value and formal economic utility. This temporal evolution is argued to let dopamine combine speed and accuracy, and it reframes aversive/salience findings as effects of the initial component.

Key findings

  • The initial dopamine component is a short-latency, short-duration activation that unselectively detects rewards, reward-predicting stimuli, unrewarded stimuli, aversive stimuli and conditioned inhibitors predicting reward omission; it is sensitive to stimulus time and codes a temporal-event prediction error.
  • The main component codes subjective value and utility: dopamine activity tracks preferred juice, risky versus safe rewards, and temporal discounting, and the second component increases monotonically with final juice amount while following nonlinear utility curvature; with equiprobable gambles, higher outcomes elicit non-monotonically varying positive prediction-error responses reflecting utility shape.
  • Aversive dopamine activations are proposed to reflect mainly the physical impact of punishers rather than aversiveness, possibly boosted by reward context and generalization; however, the paper states that some truly aversive dopamine activations can never be completely ruled out.
  • The phasic electrophysiological dopamine reward signal is described as remarkably similar across neurons with graded rather than categorical differences, whereas other dopamine functions are diverse; slow changes occur in 1–44% of dopamine neurons, about 30% reflect reward risk, and the two-component mechanism requires precise processing in the 10 ms range.

Methods

  • Review/perspective synthesizing prior electrophysiological recordings in monkeys, rats and mice, voltammetric studies, optogenetic experiments and behavioural/economic choice tasks.
  • Main analysis is conceptual integration of existing results to propose a two-component model of phasic dopamine signalling and to reinterpret the dopamine reward prediction-error response as a utility prediction-error signal.

Limitations

  • Stated: the existence of some truly aversive dopamine activations can never be completely ruled out; formal utility coding remains to be established in postsynaptic striatal and cortical neurons; and it is unclear whether all dopamine neurons, or only specific subgroups, participate in all of these functions.
  • Stated: utility experiments held risk, delay and effort cost constant, so the signal reflects income utility rather than net-benefit utility; tests should use well-defined gambles rather than unpredicted rewards in which risk is poorly defined.
  • Evident: as a review, the conclusions depend on synthesis of cited studies; the two components are often difficult to discern with simple, rapidly distinguishable stimuli and may require specific statistical methods or more demanding stimuli, and some dopamine neurons show little or no initial component.

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

Integrity signals

Registry

Crossref · 10.1038/nrn.2015.26

Cites

174 of 174 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 84 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Dopamine responses in elaborate tasks constitute standard reward prediction-error signals.

    “However, on closer inspection, dopamine responses in such elaborate tasks constitute standard reward prediction-error signals2,33,59,66,69,75,151–153.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [2] Ljungberg, T., Apicella, P. & Schultz, W. Responses of monkey dopamine neurons during learning of behavioral reactions. J. Neurophysiol. 67, 145–163 (1992). source

      Not checked in the free run.

    • cites [33] Nomoto, K., Schultz, W., Watanabe, T. & Sakagami, M. Temporally extended dopamine responses to perceptually demanding reward-predictive stimuli. J. Neurosci. 30, 10692–10702 (2010). source

      Not checked in the free run.

    • cites [59] Morris, G., Arkadir, D., Nevet, A., Vaadia, E. & Bergman, H. Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons. Neuron 43, 133–143 (2004). source

      Not checked in the free run.

    • cites [66] Schultz, W., Apicella, P. & Ljungberg, T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993). source

      Not checked in the free run.

    • cites [69] Ljungberg, T., Apicella, P. & Schultz, W. Responses of monkey midbrain dopamine neurons during delayed alternation performance. Brain Res. 586, 337–341 (1991). source

      Not checked in the free run.

    • cites [75] Enomoto, K. et al. Dopamine neurons learn to encode the long-term value of multiple future rewards. Proc. Natl Acad. Sci. USA 108, 15462–15467 (2011). source

      Not checked in the free run.

    • cites [151] Satoh, T., Nakai, S., Sato, T. & Kimura, M. Correlated coding of motivation and outcome of decision by dopamine neurons. J. Neurosci. 23, 9913–9923 (2003). source

      Not checked in the free run.

    • cites [152] Bromberg-Martin, E. S. & Hikosaka, O. Lateral habenula neurons signal errors in the prediction of reward information. Nature Neurosci. 14, 1209–1216 (2011). source

      Not checked in the free run.

    • cites [153] de Lafuente, O. & Romo, R. Dopamine neurons code subjective sensory experience and uncertainty of perceptual decisions. Proc. Natl Acad. Sci. USA 49, 19767–19771 (2011). source

      Not checked in the free run.

  • Findingcitation

    These slow changes fail to occur with more-controlled arm, mouth and eye movements in a considerable range of studies.

    “these changes fail to occur with more-controlled arm, mouth and eye movements in a considerable range of studies2,5,9,13,151,152,154”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [2] Ljungberg, T., Apicella, P. & Schultz, W. Responses of monkey dopamine neurons during learning of behavioral reactions. J. Neurophysiol. 67, 145–163 (1992). source

      Not checked in the free run.

    • cites [5] Waelti, P., Dickinson, A. & Schultz, W. Dopamine responses comply with basic assumptions of formal learning theory. Nature 412, 43–48 (2001). source

      Not checked in the free run.

    • cites [9] Lak, A., Stauffer, W. R. & Schultz, W. Dopamine prediction error responses integrate subjective value from different reward dimensions. Proc. Natl Acad. Sci. USA 111, 2343–2348 (2014). source

      Not checked in the free run.

    • cites [13] DeLong, M. R., Crutcher, M. D. & Georgopoulos, A. P. Relations between movement and single cell discharge in the substantia nigra of the behaving monkey. J. Neurosci. 3, 1599–1606 (1983). source

      Not checked in the free run.

    • cites [151] Satoh, T., Nakai, S., Sato, T. & Kimura, M. Correlated coding of motivation and outcome of decision by dopamine neurons. J. Neurosci. 23, 9913–9923 (2003). source

      Not checked in the free run.

    • cites [152] Bromberg-Martin, E. S. & Hikosaka, O. Lateral habenula neurons signal errors in the prediction of reward information. Nature Neurosci. 14, 1209–1216 (2011). source

      Not checked in the free run.

    • cites [154] Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B. & Uchida, N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482, 85–88 (2012). source

      Not checked in the free run.

  • Findingcitation

    Various subsets of dopamine neurons (1-44%) show slow, sluggish and diverse changes in the seconds time range that are inconsistently related to various aspects of behavioural task engagement and reactivity with stimulus-triggered or self-initiated arm or mouth movements.

    “various subsets of dopamine neurons (1–44%) show slow, sluggish and diverse changes in the seconds time range that are inconsistently related to various aspects of behavioural task engagement and reactivity with stimulus-triggered or self-initiated arm or mouth movements11,12,14,18”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] Schultz, W., Ruffieux, A. & Aebischer, P. The activity of pars compacta neurons of the monkey substantia nigra in relation to motor activation. Exp. Brain Res. 51, 377–387 (1983). source

      Not checked in the free run.

    • cites [12] Schultz, W. Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey. J. Neurophysiol. 56, 1439–1462 (1986). source

      Not checked in the free run.

    • cites [14] Romo, R. & Schultz, W. Dopamine neurons of the monkey midbrain: contingencies of responses to active touch during self-initiated arm movements. J. Neurophysiol. 63, 592–606 (1990). source

      Not checked in the free run.

    • cites [18] Schultz, W. & Romo, R. Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions. J. Neurophysiol. 63, 607–624 (1990). source

      Not checked in the free run.

  • Findingcitation

    Dopamine neurons contrast strongly with non-dopamine neurons in the striatum and frontal cortex, which show wide varieties of activations and depressions at different time points before and after different stimuli and behavioural events.

    “In this respect, dopamine neurons contrast strongly with non-dopamine neurons in the striatum and frontal cortex, which show wide varieties of activations and depressions at different time points before and after different stimuli and behavioural events114,147–149.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [114] Schultz, W. Neuronal reward and decision signals: from theories to data. Physiol. Rev. 95, 853–951 (2015). source

      Not checked in the free run.

    • cites [147] Fuster, J. M. Unit activity of prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J. Neurophysiol. 36, 61–78 (1973). source

      Not checked in the free run.

    • cites [148] Apicella, P., Scarnati, E., Ljungberg, T. & Schultz, W. Neuronal activity in monkey striatum related to the expectation of predictable environmental events. J. Neurophysiol. 68, 945–960 (1992). source

      Not checked in the free run.

    • cites [149] Hollerman, J. R., Tremblay, L. & Schultz, W. Influence of reward expectation on behavior-related neuronal activity in primate striatum. J. Neurophysiol. 80, 947–963 (1998). source

      Not checked in the free run.

  • Findingreasoning

    The least diverse of dopamine's functions are the phasic electrophysiological dopamine responses, whose latency, duration and type of information coding varies only in a graded, not categorical, manner between neurons.

    “The least diverse of dopamine’s functions are the phasic electrophysiological dopamine responses, whose latency, duration and type of information coding varies only in a graded (not categorical) manner between neurons.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingreasoning

    In contrast to the phasic dopamine reward prediction-error signal, all other aspects of dopamine function are diverse, including dopamine neuron morphology, electrophysiology, neurochemistry, connectivity and contribution to behaviour.

    “In contrast to the phasic dopamine reward prediction-error signal, all other aspects of dopamine function are diverse, including dopamine neuron morphology, electrophysiology, neurochemistry, connectivity and contribution to behaviour.”
    • Also stated in: § Conclusions and future directions · plain
      “however, all other aspects of dopamine function are as diverse as in other neuronal systems.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Voltammetric studies in rats show similarly slow striatal dopamine increases with movements towards cocaine levers and with reward proximity and value.

    “Voltammetric studies in rats show similarly slow striatal dopamine increases with movements towards cocaine levers155 and with reward proximity and value156”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Stuber, G. D., Wightman, R. M. & Carelli, R. M. Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens. Neuron 46, 661–669 (2005). source

      Not checked in the free run.

    • cites [156] Howe, M. W., Tierney, P. L., Sandberg, S. G., Phillips, P. E. M. & Graybiel, A. M. Prolonged dopamine signalling in striatum signals proximity and value of distant rewards. Nature 500, 575–579 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Specific learning deficits occur in mice in which NMDA-receptor knockout in dopamine neurons results in reduced dopamine burst activity, suggesting a connection between phasic dopamine activity and the learning of specific tasks.

    “specific learning deficits do occur in mice in which NMDA-receptor knockout in dopamine neurons results in reduced dopamine burst activity, suggesting a connection between phasic dopamine activity and the learning of specific tasks128.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [128] Zweifel, L. S. et al. Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior. Proc. Natl Acad. Sci. USA 106, 7281–7288 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    The phasic dopamine reward signal is remarkably similar across neurons and shows graded rather than strictly categorical differences.

    “Altogether, the phasic dopamine reward signal is remarkably similar across neurons and so far seems to show graded rather than strictly categorical differences.”
    • Also stated in: § Dopamine diversity · plain
      “The phasic electrophysiological dopamine reward signal is remarkably similar across neurons and shows graded rather than strictly categorical differences.”
    • Also stated in: § Conclusions and future directions · boosted
      “the phasic reward signal has been shown to be remarkably similar between dopamine neurons and shows only graded variations that are typical for biological phenomena rather than categorical differences”
    Quote in the paperSubstantial claim

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

    Findingcitation

    More than with most other neurons, the time course of dopamine neuron function varies vastly.

    “More than with most other neurons, the time course of dopamine neuron function varies vastly1 (BOX 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Schultz, W. Multiple dopamine functions at different time courses. Ann. Rev. Neurosci. 30, 259–288 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Risky cues induce differential voltammetric dopamine responses in the nucleus accumbens core but non-differential responses in the shell.

    “risky cues induce differential voltammetric dopamine responses in the nucleus accumbens core but non-differential responses in the shell158.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [158] Sugam, J. A., Day, J. J., Wightman, R. M. & Carelli, R. M. Phasic nucleus accumbens dopamine encodes risk-based decision-making behavior. Biol. Psychiat. 71, 199–205 (2012). source

      Not checked in the free run.

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

    Findingnone given

    Like most other neurons, dopamine neurons vary in morphology, connections, neurotransmitter colocalization, receptor location, neurotransmitter sensitivity and membrane channels.

    “Furthermore, like most other neurons, dopamine neurons vary in morphology, connections, neurotransmitter colocalization, receptor location, neurotransmitter sensitivity and membrane channels.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Impulse-dependent dopamine release is heterogeneous and sensitive to varying degrees of modulation.

    “Impulse-dependent dopamine release is also heterogeneous and sensitive to varying degrees of modulation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The initial activation is sensitive to the time of stimulus occurrence and thus codes a temporal-event prediction error.

    “True to the notion that dopamine neurons are involved in temporal prediction-error coding, the initial activation is sensitive to the time of stimulus occurrence and thus codes a temporal-event prediction error33.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Nomoto, K., Schultz, W., Watanabe, T. & Sakagami, M. Temporally extended dopamine responses to perceptually demanding reward-predictive stimuli. J. Neurosci. 30, 10692–10702 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The second dopamine response component codes the subjective value of different types of rewards, risky rewards, composite rewards and delayed rewards.

    “These findings indicate that the second dopamine response component codes the subjective value of different types of rewards, risky rewards, composite rewards and delayed rewards.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The later component of the dopamine reward prediction-error response defines the function of the phasic dopamine response and reflects the evolving neuronal processing required to fully appreciate the value of the stimulus.

    “This later component — rather than the initial detection activation described above — defines the function of the phasic dopamine response and reflects the evolving neuronal processing that is required to fully appreciate the value of the stimulus.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The initial activation lasts only until the subsequent value component conveys the accurate reward value information, which remains present until the reward occurs.

    “Thus, the initial activation lasts only until the subsequent value component conveys the accurate reward value information, which remains present until the reward occurs (FIG. 5b), covering the entire period of planning, initiation, execution and outcome of action.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Higher-than-predicted rewards elicit brief dopamine activations, lower-than-predicted rewards induce decreases in activity, and accurately predicted rewards do not change the activity.

    “Higher-than-predicted rewards (generating positive prediction errors) elicit brief dopamine activations, lower-than-predicted rewards (generating negative prediction errors) induce decreases in activity (‘depressions’), and accurately predicted rewards do not change the activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Aversive stimuli induce delayed, post-stimulus dopamine release in the shell of the nucleus accumbens, the magnitude of which predicts successful punishment avoidance.

    “Correspondingly, aversive stimuli induce delayed, post-stimulus dopamine release in the shell of the nucleus accumbens63,133, the magnitude of which predicts successful punishment avoidance136.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [63] Budygin, E. A. et al. Aversive stimulus differentially triggers subsecond dopamine release in reward regions. Neuroscience 201, 331–337 (2012). source

      Not checked in the free run.

    • cites [133] Badrinarayan, A. et al. Aversive stimuli differentially modulate real-time dopamine transmission dynamics within the nucleus accumbens core and shell. J. Neurosci. 32, 15779–15790 (2012). source

      Not checked in the free run.

    • cites [136] Oleson, E. B., Gentry, R. N., Chioma, V. C. & Cheer, J. F. Subsecond dopamine release in the nucleus accumbens predicts conditioned punishment and its successful avoidance. J. Neurosci. 32, 14804–14808 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unrewarded stimuli elicit little dopamine activation when well separated from reward, but the same unrewarded stimuli effectively elicit dopamine activations when presented in the same context in which the animal receives a reward.

    “Unrewarded stimuli elicit little dopamine activation when they are well separated from reward; however, the same unrewarded stimuli effectively elicit dopamine activations when presented in the same context in which the animal receives a reward34 (FIG. 3b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Kobayashi, S. & Schultz, W. Reward contexts extend dopamine signals to unrewarded stimuli. Curr. Biol. 24, 56–62 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Recent reports that distinguished between different stimulus components of punishers suggest that the physical impact of punishers is the major determinant for dopamine activations, and the psychophysically assessed aversive nature of the punishers did not explain the recorded dopamine activations.

    “However, recent reports that distinguished between different stimulus components of punishers suggest that the physical impact of punishers is the major determinant for dopamine activations, and the psychophysically assessed aversive nature of the punishers did not explain the recorded dopamine activations25–27.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [25] Fiorillo, C. D., Song, M. R. & Yun, S. R. Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli. J. Neurosci. 33, 4710–4725 (2013). source

      Not checked in the free run.

    • cites [26] Fiorillo, C. D., Yun, S. R. & Song, M. R. Diversity and homogeneity in responses of midbrain dopamine neurons. J. Neurosci. 33, 4693–4709 (2013). source

      Not checked in the free run.

    • cites [27] Fiorillo, C. D. Two dimensions of value: dopamine neurons represent reward but not aversiveness. Science 341, 546–549 (2013). source

      Not checked in the free run.

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

    Interpretationcitation

    The slow striatal dopamine release might derive from the above-mentioned slow impulse activities or from presynaptic influences of non-dopamine terminals.

    “the release might derive from the above-mentioned slow impulse activities or from presynaptic influences of non-dopamine terminals157”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [157] Chesselet, M. F. Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neuroscience 12, 347–375 (1984). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Because aversive responses may primarily concern the initial response component, their regional distributions might be explained by varying sensitivities to stimulus intensity, reward context and reward generalization.

    “However, because aversive responses may primarily concern the initial response component25, it is possible that their regional distributions might be explained by varying sensitivities to stimulus intensity, reward context and reward generalization (FIG. 3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Fiorillo, C. D., Song, M. R. & Yun, S. R. Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli. J. Neurosci. 33, 4710–4725 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The incentive-salience hypothesis and the prediction-error account are difficult to compare and might not be mutually exclusive.

    “The incentive-salience hypothesis and the prediction-error account are difficult to compare and might not be mutually exclusive”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    A strong activation in response to the physical impact of an aversive stimulus in particularly sensitive neurons may supersede a depression reflecting the negative value, and this might appear as a categorical difference in aversive and motivational salience coding.

    “Thus, a strong activation in response to the physical impact of an aversive stimulus in particularly sensitive neurons may supersede a depression reflecting the negative value, and this might appear as a categorical difference in aversive and motivational salience coding15,23,24,134.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [15] Chiodo, L. A., Antelman, S. M., Caggiula, A. R. & Lineberry, C. G. Sensory stimuli alter the discharge rate of dopamine (DA) neurons: evidence for two functional types of DA cells in the substantia nigra. Brain Res. 189, 544–549 (1980). source

      Not checked in the free run.

    • cites [23] Brischoux, F., Chakraborty, S., Brierley, D. I. & Ungless, M. A. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc. Natl Acad. Sci. USA 106, 4894–4899 (2009). source

      Not checked in the free run.

    • cites [24] Matsumoto, M. & Hikosaka, O. Two types of dopamine neuron distinctively convey positive and negative motivational signals. Nature 459, 837–841 (2009). source

      Not checked in the free run.

    • cites [134] Lerner, T. et al. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell 162, 635–647 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Without any rewards, reward prediction errors would not occur, and the second, value response component would be absent.

    “Without any rewards, reward prediction errors would not occur, and the second, value response component would be absent”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    The existence of some truly aversive dopamine activations can never be completely ruled out.

    “however, the existence of some truly aversive dopamine activations can never be completely ruled out.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Phasic dopamine activations by aversive stimuli constitute the initial, unselective dopamine response component driven by physical impact, possibly boosted by reward context and reward generalization, rather than reflecting a straightforward aversive response.

    “The phasic dopamine activations by aversive stimuli seem to constitute the initial, unselective dopamine response component driven by physical impact25, and possibly boosted by reward context and reward generalization19, rather than reflecting a straightforward aversive response”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Fiorillo, C. D., Song, M. R. & Yun, S. R. Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli. J. Neurosci. 33, 4710–4725 (2013). source

      Not checked in the free run.

    • cites [19] Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379, 449–451 (1996). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The response to salient stimuli does not represent the full coding potential of dopamine neurons; it constitutes only the initial, undifferentiated component of the dopamine reward prediction-error signal.

    “The response to salient stimuli does not represent the full coding potential of dopamine neurons: rather, it constitutes only the initial, undifferentiated component of the dopamine reward prediction-error signal.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The ultimate function of dopamine neurons on behaviour differs depending on the anatomical projection and function of the postsynaptic neurons they are influencing.

    “Also, the ultimate function of dopamine neurons on behaviour differs depending on the anatomical projection and function of the postsynaptic neurons they are influencing.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The phasic electrophysiological dopamine reward signal affects diverse downstream dopamine and non-dopamine mechanisms, which together makes dopamine function as diverse as the function of other neuronal systems.

    “It affects diverse downstream dopamine and non-dopamine mechanisms, which together makes dopamine function as diverse as the function of other neuronal systems.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    This processing structure is well established in neurons involved in sophisticated, higher-order processes but has long been overlooked for dopamine neurons.

    “This processing structure is well established in neurons involved in sophisticated, higher-order processes but has long been overlooked for dopamine neurons.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Inhomogeneous neuronal release of acetylcholine, glutamate and substance P affects dopamine release, which, together with the heterogeneous striosome-matrix compartments, would result in diverse dopamine release.

    “Further, inhomogeneous neuronal release of acetylcholine, glutamate and substance P affects dopamine release159–161, which, together with the heterogeneous striosome-matrix compartments, would result in diverse dopamine release.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [159] Threlfell, S. et al. Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons. Neuron 75, 58–64 (2012). source

      Not checked in the free run.

    • cites [160] Chuhma, N., Mingote, S., Moore, H. & Rayport, S. Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling. Neuron 81, 901–912 (2014). source

      Not checked in the free run.

    • cites [161] Brimblecombe, K. R. & Cragg, S. J. Substance P weights striatal dopamine transmission differently within the striosome-matrix axis. J. Neurosci. 35, 9017–9023 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    According to this account, salience concerns only the initial and transient part of the dopamine response, whereas punishers activate dopamine neurons through their physical impact rather than their aversiveness.

    “According to this account, salience concerns only the initial and transient part of the dopamine response, whereas punishers activate dopamine neurons through their physical impact rather than their aversiveness.”
    Quote in the paperSubstantial claim
29 of 29

  • The authors state this as an assumption.

    Utility provides an internal, private metric for subjective reward value.

    “Probably the most important potential that utility has for neuroscience lies in the assumption that utility provides an internal, private metric for subjective reward value83.”

  • The paper relies on this without support.

    Rewards consist of distinct sensory and value components.

    “Rewards consist of distinct sensory and value components (FIG. 1).”
2 of 2

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?

  • When participants attributed outcomes to the neutral committee (their own performance), MBD activity was positively correlated with outcome.

    “When participants attributed outcomes to the neutral committee (their own performance), MBD activity was, as has been previously reported,50”

    From Two prefrontal-subcortical circuits estimate controllability and reflect its impact on learning (2026) · cites this paper as [50]

    The main component: valuation section reports that higher-than-predicted rewards elicit dopamine activation, supporting a general positive relationship between reward outcomes and dopamine activity. It does not report MBD activity in participants attributing outcomes to a neutral committee or to their own performance; those conditions are not supported by this source. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Dopamine neurons also encode prediction errors (or some attribute of prediction errors) about outcomes other than just reward, although this is still debated.

    “Thus, evidence suggests that dopamine neurons also encode PEs (or some attribute of PEs) about outcomes other than just reward (6, 10) (Figure 1B). However, it should be recognised that this is still debated (14).”

    From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [14]

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.

  • Conflicting PNAS volumes for 2011

    Minor

    The references list two different volumes for the same journal in 2011: volume 49 in reference 153 and volume 108 in reference 75. At least one volume number is inconsistent.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Pascal, B. Pensées (1658–1662) (Hackett, 2004).
  2. Bernoulli, D. Specimen theoriae novae de mensura sortis. Comentarii Academiae Scientiarum Imperialis Petropolitanae 5, 175–192 (1738); English translation available in Exposition of a new theory on the measurement of risk. Econometrica 22, 23–36 (1954).
  3. Bentham, J. An Introduction to the Principle of Morals and Legislations (Blackwell, 1948).
  4. Mas-Colell, A., Whinston, M. & Green, J. Microeconomic Theory (Oxford Univ. Press, 1995).

Cited by

Sorted by citations

Related

Authors
Schultz, W.
Affiliations
University of Cambridge (GB)
Corresponding author
Schultz, Wolfram
ORCID
Schultz, Wolfram
Venue
Nature Reviews Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2016-02-11
Volume
17
Issue
3
Pages
183-195
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
DOI
10.1038/nrn.2015.26
PMC
PMC5549862
OpenAlex
W2263610200
Cited by
1,036
References
174
Citations by year
2026: 120 · 2025: 111 · 2024: 117 · 2023: 109 · 2022: 96 · 2021: 102 · 2020: 95 · 2019: 109 · 2018: 93 · 2017: 61 · 2016: 23
FWCI
10.29
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • California Institute of Technology
  • Wellcome Trust (095495, 058365, 093270, 093875)
  • National Institutes of Health
  • National Institute of Mental Health (P50MH094258)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
dopamine, reward prediction error, midbrain dopaminergic neurons, reward processing, serial processing, stimulus detection, speed-accuracy trade-off
MeSH terms
Animals, Dopamine, Humans, Neurons, Reward, Signal Transduction

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review