Using Transcranial Magnetic Stimulation (TMS) to Relate Motor Cortex Activity to an Expected Reward

Purpose:

The purpose of this research is to understand the decision making process. Decisions are based on a complex system of rewards and punishments. By understanding the reward system and being able to measure reward expectation, it might be possible to understand decision making.

Background:

The Ventral Tegmental Area (VTA) of the brain is the reward center. It has previously been shown that there are dopaminergic connections in primates between the VTA and the Motor Cortex (M1) [1, 3]. It is hypothesized that the VTA sends signals through the dopamine pathway to M1, the part of the brain which controls movement, when rewards are expected or received in humans.

According to the hypothesis that the dopamine pathway is involved in sending signals from the VTA to M1 when rewards are expected or received, reward processing should be different in those with less dopamine than in normal controls. Because Parkinson's disease results in the degeneration of dopamine-producing neurons, Parkinson's patients were tested.

Transcranial Magnetic Stimulation is used to stimulate different parts of the brain. When the magnetic coil is held on the head, it delivers a pulse to the area in the middle of the coil. When the pulse is held over M1, it causes the subject's hand to move. This movement can be measured with electrodes. The M1 activity is therefore safely and non-invasively measured in the form of a muscle response.

The size of muscle response is controlled by the amount of inhibition. If a weak pulse (used in paired-pulse TMS) is added before the test pulse, inhibitory mechanisms in the cortex are activated. If there is dopamine present, there is even more inhibition. Therefore, single- and paired-pulse TMS was used. [2]

Methods:

During the experiment, subjects played a slot machine simulation in which they won actual money (the reward). After two out of three slot machine barrels stopped, the TMS was delivered. The TMS was delivered at this point because the subject would:

1) Have a match, and expect that the third barrel might have a matching fruit; or 2) There would be a "no money sign," in which the subject would not expect a reward.

The hypothesis being studied calls for M1 involvement in the reward system. Therefore, its activity should vary when a reward is expected, as opposed to when there is no reward expectation. This variation in the activity occurs in the VTA, and, according to the hypothesis, should occur in M1 during reward processing. It has been shown [2] that in normal controls, there is greater inhibition when a reward is expected. This can be explained by the fact that dopamine (which is inhibitory) is involved with reward processing.

Using TMS, M1 activity during the slot machine simulation was compared in normal controls, aged 54-80, to Stage I and II Parkinson's Patients off medication, as well as on Levodopa, and on Pramipexole. These medications should increase dopamine levels in M1, and increase inhibition when the conditioning pulse is present.

Results and Conclusions:

The results suggest that, unlike normal controls of the same age range, Parkinson's patients have no significant differences in M1 activity when there is reward expectation or no reward expectation. This supports the hypothesis that dopamine pathways, which are destroyed in patients with Parkinson's disease, are part of normal reward processing.

Parkinson's medications, such as Levodopa and Pramipexole, are thought to restore reward processing. M1 activity returned close to that of the normal controls after either Levodopa or Pramipexole was administered. The medications had more of a normalizing effect on M1 activity levels in Stage I Parkinson's patients, as opposed to the more progressed Stage II Parkinson's patients.

Impaired reward processing in patients with Parkinson's disease supports the hypothesis that M1 receives signals from the VTA through dopamine pathways. Since dopamine precursors and agonists restore the reward processing, this further supports the hypothesis.

References:

1. Gaspar, P., I. Stepniewska, J.H. Kaas. "Topography and Collateralization of the Dopamineric projections to Motor and Lateral Prefrontal Cortex in Owl Monkeys." The Journal of Comparative Neurology 325(1992): 1-21.

2. Kapogiannis, Dimitrios, Paul Campion, Jordan Grafman, Eric M. Wassermann. "Reward-related Activity in the Human Motor Cortex." European Journal of Neuroscience 27(2008): 1836-1842.

3. Williams, Mark S., Patricia S. Goldman-Rakic. "Characterization of the Dopaminergic Innervation of the Primate Frontal Cortex Using a Dopamine-specific Antibody." Cerebral Cortex 3(1993): 199-222