Research reported by investigators at Cedars-Sinai Medical Center and at the California Institute of Technology has provided new insights into how the brain weighs decisions involving what people like or value, such as choosing which book to read, which restaurant to pick for lunch, or even which slot machine to play in a casino. The results of the human study, which involved recording the activity of individual neurons in specific areas of the brain, could ultimately help researchers develop new treatments for complex neurological disorders.

“Learning how the brain makes these kinds of choices could help us better understand neurological disorders including addiction and obsessive-compulsive disorder, because all of these conditions can involve a person making the same choice over and over to their detriment,” said research lead Ueli Rutishauser, PhD, who is director of the Center for Neural Science and Medicine, and professor of Neurology, Neurosurgery and Biomedical Sciences at Cedars-Sinai. Rutishauser is senior author of the researchers’ published paper in Nature Human Biology, which is titled “Neurons in human pre-supplementary motor area encode key computations for value-based choice.”

Humans and other animals can make decisions in a manner that maximizes the chance of obtaining rewards, and Rutishauser and colleagues were interested in examining decisions called value-based choices, where there is not necessarily a right or wrong option. As the authors explained, computational theories suggest that the process of decision making relies on a number of variables, and particularly the ‘expected value’ (EV) associated with an option. “Adaptive behaviour in real-world environments requires that choices integrate several variables, including the novelty of the options under consideration, their expected value and uncertainty in value estimation.”

Most human studies have used non-invasive methods, such as functional MRI (fMRI) to investigate how the different regions of the brain may be involved in integrating these variables and making a decision. Such studies have highlighted roles for the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area (preSMA) in value-based decision making. “Overall, these areas encode decision variables such as EV, uncertainty and outcomes, while novelty-related effects have also been found in the dopaminergic midbrain and striatum,” the team wrote.

The newly reported study involved 20 human volunteers, who were all patients with epilepsy, and who were hospitalized so that doctors could monitor their brain activity to determine the focal points of their seizures. This allowed investigators to record the activity of individual neurons within specific areas of the participant’s brain while the individual played a computer slot-machine game. The authors explained, “ … we recorded single neurons in preSMA, dACC and vmPFC while human patients with drug-resistant epilepsy undergoing invasive electrophysiological monitoring performed a decision-making task specifically designed to dissociate EV, novelty and estimation uncertainty, which we interchangeably refer to as ‘uncertainty’ …”

The game, called “two-armed bandit,” let participants choose one of two simulated slot machines in each round. Participants pushed a button to select their “bandit,” which then either paid out or did not. The bandits had unique markings, so the participants could tell whether they had played each one before, and participants played several rounds over a 30-minute period.

Rutishauser explained the factors involved in making value-based choices. One is familiar options. “If participants had chosen a bandit several times before, they had a fairly good idea of how often it was a winner,” Rutishauser said. Another is uncertain options, so, as Rutishauser further noted, “For bandits they had only played a few times, participants were less certain of their prospect of a win.”  And the third factor is new options. “When a new bandit appeared for the first time, participants had to decide whether to choose a familiar bandit or risk choosing a new one. Sometimes it just feels good to do something new, and that has its own intrinsic value.”

Previous fMRI studies had suggested that the vmPFC area of the brain plays a primary role in weighing these factors. But in a recent study, Cedars-Sinai investigators determined that a completely different area, the pre-SMA, takes the lead.

By recording single-neurons in the study participants, the investigators were able to see that while the vmPFC signaled the “novelty” value of new bandits that appeared, it was the preSMA that calculated which option had the best chance of yielding the highest reward. And that signal was the basis on which participants made their choices.

“Previous studies weren’t giving us a complete picture and couldn’t draw the distinction we could here,” said Tomas Aquino, PhD, a postdoctoral fellow in the Rutishauser Lab and first author of the study. “Since our single-neuron recordings are more sensitive than other, more common methods, we could measure directly how preSMA neurons compute the value of each option and determine participants’ choices.” The authors further stated “… this study afforded us an unparalleled opportunity to investigate the role of human prefrontal neurons across multiple stages of value-based decision-making: from the representation of individual decision variables, through to the integration of these variables into a putative utility signal, up to choice and ultimately feedback.”

Both the vmPFC and the preSMA are part of the brain’s frontal lobe, and both have been implicated in planning and decision-making activities, but through this study, for the first time, investigators were able to tease out their separate roles. This new discovery joins a number of other recent findings indicating that preSMA is critically important to human decision-making.. “ …  our results situate the human preSMA as an important centre for value-based decision-making, with a robust encoding of decision variables and, most crucially, an integrated utility signal at the single-neuron level that can be leveraged to inform choice,” the scientists noted. “While vmPFC neurons encoded pre-decision and post-decision variables contingent on choice, neither this region nor the dACC showed an equivalently robust encoding of pre-decision integrated utilities or the choice itself.”

Co-author Adam Mamelak MD, director of the Functional Neurosurgery Program at Cedars-Sinai, added, “The unique window into the human brain that is opened by these single-neuron recordings continues to deepen our understanding of the precise mechanisms behind cognitive processes. These continued gains in understanding are the key to finding new treatments for complex neurological disorders and improving the lives of patients.”

This research is part of a long-standing collaboration between Cedars-Sinai and co-senior author John O’Doherty, PhD, Fletcher Jones Professor of Decision Neuroscience at the California Institute of Technology.

Previous articleModerna, Generation Bio Launch Up-to-$1.9B Non-Viral Genetic Medicines Collaboration
Next articleAlzheimer’s Biomarker Kit for Point-of-Care Testing Receives Grant