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Research ArticleNew Research, Cognition and Behavior

Deep-Brain Stimulation of the Subthalamic Nucleus Selectively Decreases Risky Choice in Risk-Preferring Rats

Wendy K. Adams, Cole Vonder Haar, Melanie Tremblay, Paul J. Cocker, Mason M. Silveira, Sukhbir Kaur, Christelle Baunez and Catharine A. Winstanley
eNeuro 14 July 2017, 4 (4) ENEURO.0094-17.2017; https://doi.org/10.1523/ENEURO.0094-17.2017
Wendy K. Adams
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Cole Vonder Haar
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Melanie Tremblay
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Paul J. Cocker
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Mason M. Silveira
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Sukhbir Kaur
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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Christelle Baunez
2Institut de Neurosciences de la Timone, UMR7289 Centre National de la Recherche Scientifique and Aix-Marseille Université, 13005, Marseille, France
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Catharine A. Winstanley
1Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T 1Z3, Canada
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  • Figure 1.
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    Figure 1.

    Task schematic of the rGT. A nose poke response in the food tray extinguished the traylight and initiated a new trial. After an ITI of 5 s, four stimulus lights were turned on in holes 1, 2, 4, and 5, each of which was associated with a different number of sugar pellets (one to four pellets, labeled P1-P4). The animal was required to respond at a hole within 10 s. This response was then rewarded or punished depending on the reinforcement schedule for that option (indicated by the probability of a win or loss in brackets). If the animal was rewarded, the stimulus lights turned off and reward was delivered. If the animal “lost,” the stimulus light in the chosen hole flashed at a frequency of 0.5 Hz for the duration of the punishing timeout, and all other lights were extinguished. The order of the options from left to right was counterbalanced across the cohort (version A as shown, version B: 4, 1, 3, 2). The maximum number of pellets available per 30-min session shows that P1 and P2 were better than P3 and P4. The percentage choice of the different options was the primary dependent variable. A score variable was also calculated, as for the IGT, to determine the overall level of risky choice as follows: [(P1 + P2) – (P3 + P4)]. A negative score indicated a preference for the risky options, and rats were categorized as optimal decision-makers or risk-preferring rats accordingly. Adapted with permission from Barrus et al. (2015).

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    Figure 2.

    Experimental time line delineating the duration and order of each phase of the study.

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    Figure 3.

    Histologic verification of electrode location. The location of all acceptable electrode tips within the STN are shown in black circles. Coordinates are relative to bregma. Plates modified from Paxinos and Watson (1998).

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    Figure 4.

    Effects of STN-DBS on decision-making variables. While STN-DBS did not alter relative preference for any of the four options in optimal decision makers (A), this manipulation significantly increased optimal choice in risk-preferring rats across the last seven DBS sessions, as indicated by increased choice of the best option, P2 (B), and a resulting increase in the score variable (C). This effect was no longer evident once stimulation was no longer applied during the rGT. Data shown are group mean ± SEM.

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    Figure 5.

    Weight gain throughout food restriction and pair-housing. Body weight was recorded 3–5 d per week during the first month of food restriction, and at least once per week for the duration of the experiment. As expected, all rats showed robust weight gain over time, and the rate or degree of weight gain did not differ between optimal decision-makers and risk-preferring rats. Data shown are group mean ± SEM.

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    Figure 6.

    Effects of STN-DBS on non-choice variables. Regardless of baseline decision-making strategy, STN-DBS transiently decreased premature responding, an effect that reached significance in sessions four through six (A), and significantly increased omissions (B) across all sessions in which stimulation was applied. While STN-DBS did not alter the number of trials completed by optimal decision-makers, risk-preferring rats tended to complete more trials in sessions 4-6 of stimulation (C), matching the epoch in which the most dramatic improvements in decision making were observed (Fig. 4). None of these effects were still evident in the three sessions immediately following the final DBS session. Data shown are group mean ± SEM.

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    Table 1.

    Latencies to make a choice and collect reward during the different phases of the experiment in optimal decision-makers and risk-preferring rats

    Choice latency (s)Reward collection latency (s)
    PhaseOptimalRisk preferringOptimalRisk preferring
    Post-op BL1.25 (0.18)1.58 (0.21)1.56 (0.10)1.25 (0.17)
    Mock DBS1.27 (0.16)1.73 (0.14)1.61 (0.10)1.33 (0.25)
    DBS S1-32.36 (0.22)2.33 (0.16)2.58 (0.35)2.05 (0.29)
    DBS S4-62.16 (0.20)2.81 (0.26)2.38 (0.22)2.46 (0.41)
    DBS S7-102.28 (0.30)2.92 (0.38)2.22 (0.25)2.55 (0.42)
    Post DBS S1-31.26 (0.20)1.79 (0.37)1.65 (0.10)1.45 (0.21)
    • Bold type indicates a significant difference (p < 0.05) from the mock DBS sessions. Data are mean (SEM).

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Deep-Brain Stimulation of the Subthalamic Nucleus Selectively Decreases Risky Choice in Risk-Preferring Rats
Wendy K. Adams, Cole Vonder Haar, Melanie Tremblay, Paul J. Cocker, Mason M. Silveira, Sukhbir Kaur, Christelle Baunez, Catharine A. Winstanley
eNeuro 14 July 2017, 4 (4) ENEURO.0094-17.2017; DOI: 10.1523/ENEURO.0094-17.2017

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Deep-Brain Stimulation of the Subthalamic Nucleus Selectively Decreases Risky Choice in Risk-Preferring Rats
Wendy K. Adams, Cole Vonder Haar, Melanie Tremblay, Paul J. Cocker, Mason M. Silveira, Sukhbir Kaur, Christelle Baunez, Catharine A. Winstanley
eNeuro 14 July 2017, 4 (4) ENEURO.0094-17.2017; DOI: 10.1523/ENEURO.0094-17.2017
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Keywords

  • addiction
  • basal ganglia
  • decision making
  • impulsivity
  • Parkinson’s disease
  • rat gambling task

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