Deep brain stimulation study models impulsivity and risk aversion

Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes into specific regions of the brain and then stimulating these regions with high-frequency electrical impulses. This procedure is a highly effective therapeutic intervention for a variety of serious neurological and psychiatric disorders, including Parkinson’s disease and obsessive-compulsive disorder (OCD).

Researchers from Shanghai Jiao Tong University School of Medicine and the University of Cambridge recently used DBS to study two opposing behavioral patterns in decision-making, namely impulsivity and risk aversion.

Their article, published in Nature Mental Healthidentifies new objective (i.e. generally applicable to all human beings) and subjective (i.e. different between individuals) markers of risk-taking.

“Why do we make impulsive decisions that are risky too quickly, without restraint or choosing immediate gratification?” Valerie Voon, co-author of the study, told Medical Xpress. “My research group studies impulsivity and how emotions or incentives can influence our decisions, particularly in the case of addictions and compulsivity.”

“We are interested in the overlap between illegal (stimulants, heroin), legal (nicotine, alcohol) and behavioral addictions, such as gambling, compulsive sexual behaviors or compulsive behaviors like OCD.”

The main goal of Voon and colleagues’ recent study was to investigate risk-taking, the tendency to make decisions with an expected reward or punishment in situations where outcomes are either easy to predict or difficult or impossible to predict. To do this, the team stimulated the subthalamic nucleus (STN) of study participants using deep brain stimulation.

“We know that DBS can increase specific forms of impulsivity: so-called conflict impulsivity, STN DBS allows for faster choices between two difficult choices,” Voon said.

“This is not always negative and can be functional. For example, the choices of patients diagnosed with OCD are pathologically slowed. STN DBS can normalize this, so that their choices become faster and closer to those of healthy individuals.”

Previous studies have shown that deep brain stimulation targeting the STN can also increase risk aversion, making individuals more likely to make safer (i.e., less risky) choices. This means that it simultaneously influences two different dimensions of impulsivity, helping individuals make difficult decisions more quickly while choosing the less risky choice.

“The STN is a critical brain region for Parkinson’s and OCD,” Voon explains. “It’s about the size of a pea and is located in the indirect inhibitory pathway of the frontostriatal circuit. It plays an integrative role in allowing us to calibrate our actions and decisions, speeding up, slowing down, or braking, depending on how quickly we need to make decisions.”

Voon and his research group wanted to better understand the brain waves that underlie impulsivity during different types of decision-making. Using DBS electrodes implanted in their participants’ STN, they were able to gather new insights into how different individuals’ brains process different aspects of risky decision-making.

“We also studied what happens if we stimulate the STN for one second, particularly in terms of its effect on risk seeking and brain waves,” Voon said. “This then allows us to explore the causal role or importance of the STN in risk-seeking behavior.”

To conduct their study, the researchers recruited a group of participants with Parkinson’s disease who had already had electrodes implanted in their brains as part of their clinical treatment. These same electrodes were used to record the activity of their STN while they played a video game.

“We asked patients to play a simple card game, which is commonly used as a drinking game,” Voon says. “We showed them two decks of cards: one open and one closed. We then asked them to bet whether they thought the next card revealed would be higher. If the card they were shown was a low number, such as a 3, they were more likely to bet that the next card would be higher.”

By recording participants’ brain activity as they played this decision-making game, the team was able to observe what was happening in their brains when they expected to win or lose their bets. They were able to compare the brain activity recorded in cases where the outcomes were uncertain (for example, when the card shown to participants was a 4, 5, or 6) to that recorded when the outcomes were much more predictable (for example, when the card shown was a 1 or 9).

“We were also interested in what we called ‘subjective risk,’ which is what the brain looks like when we are more willing or more reluctant to take risks,” Voon said. “To study this, we stimulated the subthalamic nucleus for one second while patients were trying to make a decision.”

The brain activity recorded during the team’s experiments yielded a number of interesting insights. First, the researchers observed varying levels of activity in the STN depending on whether participants expected to win or lose a bet and on the degree of uncertainty associated with a given choice.

“We also showed that this individual subjective tendency to seek or avoid risk is associated with a different brain wave,” Voon explained. “Essentially, our results suggest that different individuals’ brains encode differently what is actually happening (expectation of winning/losing or uncertainty), as well as our actual preferences and tendencies (risk seeking/aversion).”

Interestingly, Voon and his research group showed that STN stimulation decreased risk seeking. This stimulation was also linked to an increase in a specific frequency (theta 4-8 Hz) in the STN, which when increased led individuals to make safer choices more quickly.

STN stimulation sites also appear to impact participants’ behavior. Stimulation of the upper STN segment, known to be linked to movement and commonly targeted in DBS treatments for Parkinson’s disease, appears to influence risk aversion. In contrast, stimulation of the lower STN, linked to emotions and decisions, appears to increase risk-seeking decisions.

“We know that clinical stimulation of these limbic and decision-making regions of the STN can sometimes be associated with a side effect of hypomania, which clinically is associated with greater risk seeking,” Voon said.

“We have previously shown that stimulation of this region is also associated with more positive emotions, consistent with hypomania. In addition, we found that different parts of the midline of the brain are linked to whether we are more risk-seeking (the front of the brain) or more fearful of it (the back of the brain).”

Recent work by this team of researchers shows that STN activity varies greatly during risk-related decision-making depending on whether the individual expects to win, lose, or is uncertain of the outcome. This activity also appears to vary depending on whether individuals are more or less likely to take risks.

“Stimulating the STN increases risk aversion, or the tendency to choose the safer, less risky choice, which is associated with an increase in a specific brain wave, theta activity,” Voon said. “Additionally, where we stimulate may have different effects on our tendency to seek or avoid risk.”

The results of this study could soon contribute to the understanding of impulsivity, which is associated with various psychiatric and neurological disorders. Voon and his research group are now trying to use their observations to design more effective interventions for some of these disorders, as well as to reduce the side effects of deep brain stimulation, such as hypomania.

The researchers are currently recruiting new participants for a DBS study focused on opioid and alcohol addiction. This study could provide additional insights into unique neural markers of addiction-related impulsivity.

“I am leading this study across Cambridge, Kings College Hospital and Oxford,” Voon added. “In these new experiments, we are stimulating two different brain regions involved in reward, motivation and self-control. Deep brain stimulation is very effective for Parkinson’s disease and OCD, and preliminary studies suggest it may also be effective for addictions. We will be conducting a randomized controlled clinical trial to examine the effectiveness of deep brain stimulation for addictions.”

In their upcoming studies, Voon and his colleagues will focus both on the risk-taking processes studied in their recent work and on other dimensions of decision-making that are specifically related to addiction. These additional dimensions include how the brains of substance-dependent people respond to alcohol- and drug-related triggers, their mood, and other tendencies toward impulsive or compulsive decision-making.

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