Investing in the future: stimulation of the medial prefrontal cortex reduces discounting of delayed rewards

Abstract

Generally, rewards that are received sooner are often preferred over future rewards, and the time between the choice and the reception of the reward is an important factor that influences our decisions, a phenomenon called delay discounting (DD). In DD, the medial prefrontal cortex (MePFC) and striatal dopamine neurotransmission both play an important role. We used repetitive transcranial magnetic stimulation (rTMS) to transiently activate the MePFC to evaluate its behavioral effect on the DD paradigm, and subsequently to measure its effect on striatal dopamine. Twenty-four right-handed young healthy subjects (11 females; age: 22.1±2.9 years) underwent DD following 10 Hz-rTMS of the MePFC and vertex stimulation (control condition). Thereafter, 11 subjects (5 females; age: 22.2±2.87 years) completed the PET study at rest using [(11)C]-(+)-PHNO following 10 Hz-rTMS of the MePFC and vertex. Modulation of the MePFC excitability influenced the subjective level of DD for delayed rewards and interfered with synaptic dopamine level in the striatum. The present study yielded findings that might reconcile the role of these areas in inter-temporal decision making and dopamine modulation, suggesting that the subjective sense of time and value of reward are critically controlled by these important regions.

Figure 1

Stimulation target areas and protocol. (a) The MePFC (upper figure) and vertex (lower figure) target area mapped on Colin brain (b) experimental procedures for behavioral (upper figure) and PET imaging (lower figure) studies. For each rTMS session, 15 10-pulse trains of 1-s duration were delivered at a stimulation frequency of 10 Hz, with a between-train interval of 10 s.

Figure 2

Effect of rTMS on DD ln(k) for each rTMS condition (n=24). rTMS over the MePFC (compared with vertex-rTMS) significantly affected DD rate and reduced log-transformed k value (ln(k)) compared with control site stimulation (P<0.01).

Figure 3

[¹¹C]-(+)-PHNO PET imaging results (n=11). (a) Anatomical representation of the basal ganglia (upper row) and MePFC-rTMS induced displacement of DA in the striatum with a reduction in [¹¹C]-(+)-PHNO BP specifically in the bilateral dorsal putamen (DPu) and bilateral dorsal/ventral globus pallidus (GP) (compared with vertex-rTMS) (lower row). Color bar indicates t-statistics (b). The bars display BPs extracted from statistically significant clusters showing the [¹¹C]-(+)-PHNO BP reduction between MePFC and vertex control stimulations in left and right striatum. The mean Δ%BP was −13.1±8.1% in the left and −13.0±8.8% in the right striatal cluster.

Figure 4

Correlation showing the inverse relationship between Δ%BP of GP and Δ%BP of the NAcc in the left hemisphere (P<0.05). MePFC rTMS-induced displacement of DA in the dorsal striatum paralleled the lack of consistent DA release in the NAcc.

Figure 5

Dopamine-behavioral relationships showing changes in DD rate in the left (a) and right (b) GP. A quadratic relationship was found between [¹¹C]-(+)-PHNO Δ%BP and % changes of ln(k) in the bilateral GP (R²=0.74, F_2,8=8.17, P<0.01 for left; R²=0.84, F_2,8=21.39, P<0.01 for right).