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Volumn 319, Issue 5867, 2008, Pages 1264-1267

BOLD responses reflecting dopaminergic signals in the human ventral tegmental area

Author keywords

[No Author keywords available]

Indexed keywords

DOPAMINE;

EID: 40049086223     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1150605     Document Type: Article
Times cited : (546)

References (51)
  • 4
    • 40049096006 scopus 로고    scopus 로고
    • 3, which is inadequate for imaging from the VTA and only gives a small number of measurements in the SN.
    • 3, which is inadequate for imaging from the VTA and only gives a small number of measurements in the SN.
  • 5
    • 2942617032 scopus 로고    scopus 로고
    • B. Seymour et al., Nature 429, 664 (2004).
    • (2004) Nature , vol.429 , pp. 664
    • Seymour, B.1
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    • B. H. Schott et al., Brain 130, 2412 (2007).
    • (2007) Brain , vol.130 , pp. 2412
    • Schott, B.H.1
  • 23
  • 27
    • 40049090806 scopus 로고    scopus 로고
    • The reward prediction error term depends on time through a value function, V(t), that gives the reward expected into the infinite future. It is the time derivative of V(t), dV(t)/dt, that gives the reward expected at time t and is hypothesized to be communicated to midbrain dopamine nuclei (1).
    • The reward prediction error term depends on time through a value function, V(t), that gives the reward expected into the infinite future. It is the time derivative of V(t), dV(t)/dt, that gives the reward expected at time t and is hypothesized to be communicated to midbrain dopamine nuclei (1).
  • 30
    • 40049096454 scopus 로고    scopus 로고
    • The reward prediction error signal could also be generated by recurrent collaterals in the VTA
    • The reward prediction error signal could also be generated by recurrent collaterals in the VTA.
  • 37
  • 38
    • 40049089738 scopus 로고    scopus 로고
    • The VTA and SN include a variety of neuron types, not just dopaminergic neurons, and the BOLD response measured from these nuclei presumably reflects the composite activity of these neurons. Nevertheless, as discussed further on, our findings suggest that the BOLD responses we observed reflected a dominant, if not exclusive, influence of dopamine neuron activity. In addition, the methods we used were not optimized for detecting responses in the SN or VStr. Because of the cardiac gated functional data acquisition, image acquisition time was necessarily less than the time between heartbeats, which limited the number of slices we were able to acquire (see supporting online material for details, Slices were placed so as to optimize our coverage of the VTA. The VTA is small and thus, even with the number of slices we were limited to by the participant's heart rate, we were able to record from the entire region. However, we were only able to record from portions of the striatum (Fig. 3A) an
    • The VTA and SN include a variety of neuron types, not just dopaminergic neurons, and the BOLD response measured from these nuclei presumably reflects the composite activity of these neurons. Nevertheless, as discussed further on, our findings suggest that the BOLD responses we observed reflected a dominant, if not exclusive, influence of dopamine neuron activity. In addition, the methods we used were not optimized for detecting responses in the SN or VStr. Because of the cardiac gated functional data acquisition, image acquisition time was necessarily less than the time between heartbeats, which limited the number of slices we were able to acquire (see supporting online material for details). Slices were placed so as to optimize our coverage of the VTA. The VTA is small and thus, even with the number of slices we were limited to by the participant's heart rate, we were able to record from the entire region. However, we were only able to record from portions of the striatum (Fig. 3A) and SN. Given this limited coverage of the striatum and SN, our measurements from these structures are likely to have been underpowered.
  • 39
    • 40049099106 scopus 로고    scopus 로고
    • A recent study reports an equal BOLD-fMRI response in the VStr to delivery of juice and water (40). Consequently, we included both juice and water trials in our study to keep participants as interested as possible. Juice and water trials were randomized across all scanning runs, and results are collapsed across both trial types.
    • A recent study reports an equal BOLD-fMRI response in the VStr to delivery of juice and water (40). Consequently, we included both juice and water trials in our study to keep participants as interested as possible. Juice and water trials were randomized across all scanning runs, and results are collapsed across both trial types.
  • 41
    • 40049094020 scopus 로고    scopus 로고
    • In addition to regressors for reward prediction errors, we also included regressors for the display of the visual cue and for dV/dt. No brain regions showed a significant response to the display of the cue during and after training [compare to (37, however, the visual cortex was not imaged in this experiment due to slice positioning Fig. 1C, Additionally, no brain regions showed a significant response to dV/dt
    • In addition to regressors for reward prediction errors, we also included regressors for the display of the visual cue and for dV/dt. No brain regions showed a significant response to the display of the cue during and after training [compare to (37)]; however, the visual cortex was not imaged in this experiment due to slice positioning (Fig. 1C). Additionally, no brain regions showed a significant response to dV/dt.
  • 42
    • 40049109357 scopus 로고    scopus 로고
    • Mean event-related BOLD responses were calculated for the receipt of expected and unexpected rewards see supporting online material for details on impulse response function generation and for plots of time course data, The areas under the response curves were calculated from time t, 3 s to 7 s after reward receipt and correlated across subjects in the VTA and VStr. This segment of the response curves was selected because it corresponds to the time points of the peak in the BOLD response
    • Mean event-related BOLD responses were calculated for the receipt of expected and unexpected rewards (see supporting online material for details on impulse response function generation and for plots of time course data). The areas under the response curves were calculated from time t = 3 s to 7 s after reward receipt and correlated across subjects in the VTA and VStr. This segment of the response curves was selected because it corresponds to the time points of the peak in the BOLD response.
  • 43
    • 40049092913 scopus 로고    scopus 로고
    • In temporal difference reinforcement learning, the reward prediction error is given by δ(t, r(t, E{r(t, 1)|St+1, E{r(t)|St, δ(t) is the reward prediction error, r(t) is the reward value at time t, and E{r(t)|St}is the expected value of reward given the history of stimuli up to time t, which is termed St (1, 2, When the stimulus is shown, the BOLD response should be proportional to δ(t, E{rt, 1, St+1} because we assume that the expected value is constant or zero between events. We represented the BOLD response to the display of the first number as not varying in magnitude because the probability of winning is unknown until participants press a button indicating their decision. It is important to note t
    • t) and increases linearly with the probability of winning.
  • 51
    • 40049090351 scopus 로고    scopus 로고
    • We thank V. Napadow for access to the brainstem normalization algorithm ahead of its publication and for guidance with data acquisition. We thank C. L. Buck, K. Lowenberg, and E. Barkley-Levenson for help with participant recruitment and scanning. We also thank R. Tengi for helping manage the large amount of disk space necessary to accomplish data analysis. This work was supported by NIH grants P50 MH062196, J.D.C, T32 MH065214, J.D.C, and F32 MH072141 S.M.M
    • We thank V. Napadow for access to the brainstem normalization algorithm ahead of its publication and for guidance with data acquisition. We thank C. L. Buck, K. Lowenberg, and E. Barkley-Levenson for help with participant recruitment and scanning. We also thank R. Tengi for helping manage the large amount of disk space necessary to accomplish data analysis. This work was supported by NIH grants P50 MH062196 ( J.D.C.), T32 MH065214 ( J.D.C.), and F32 MH072141 (S.M.M.).


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