A noninvasive, low-intensity ultrasound method that targets nerve cells, or neurons, can alter brain function to influence decision-making.

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New research shows how a brain area called the anterior cingulate cortex controls a type of reasoning known as counterfactual thinking.

Scientists have demonstrated the technique in a recent study, in which they disrupted “counterfactual thinking” in primates.

Counterfactual thinking, or counterfactual reasoning, is a type of decision-making that involves considering options that are not available now but could be in the future.

For example, a person working indoors on a sunny day who says to themselves, “I could be outside enjoying the sunshine,” is engaging in counterfactual thinking.

The recent study is the first to show that a frontal brain region known as the anterior cingulate cortex can regulate counterfactual thinking.

In a paper in Nature Neuroscience, the authors describe how they altered counterfactual thinking in macaque monkeys by targeting neurons in their anterior cingulate cortex with noninvasive, low-intensity ultrasound.

Research on decision-making has tended to focus on brain circuits that control responses to current stimuli. However, the authors note that “Animals often pursue behaviors for which there is currently no sensory evidence.”

They argue that, to be able to do this, animals have to maintain “internal representations” of choices, “even when these choices are unavailable.”

In other words, animals must have some capacity for counterfactual thinking, or thinking about choices that are unrelated to current experience.

“This is a really exciting study for two main reasons,” says lead and corresponding study author Elsa Fouragnan, Ph.D., who works at the University of Plymouth School of Psychology, in the United Kingdom.

The first reason for being excited by the study, she explains, is because the findings reveal that “the cingulate cortex is crucial to help switch to better alternatives.”

And the second reason, she adds, is because the results show that “low-intensity ultrasound can be used to reversibly change brain activity in [a] very precise part of the brain.”

There is a growing need for nonsurgical brain stimulation tools. There is potential for such methods to improve treatment outcomes safely and with minimum side effects.

Low-intensity, focused ultrasound is “gaining traction” as such an approach. Previous studies have shown that it can alter activity in mammal brains noninvasively, both by stimulating and blocking signals.

Some studies have also shown that ultrasound can influence activity in the outer layers and also deep inside the human brain.

The recent study sheds light on how activity in the anterior cingulate cortex influences decision-making.

It suggests that, if this part of the brain does not function properly, it could prevent an individual from being able to switch to a better option, even when it becomes available.

Experts believe that this type of brain dysfunction could be the reason why people with certain psychiatric illnesses remain trapped in unhelpful habits.

Fouragnan and colleagues investigated these possibilities further by studying the macaques as they searched for and selected a treat from a range of options.

The monkeys rapidly learned which of the options they preferred, but when it came to exercising choice, it was not always available. However, they did “keep it in mind” for when it was next available.

The researchers then investigated how the monkeys “maintained representations of the value of counterfactual choices – choices that could not be taken at the current moment but which could be taken in the future.”

Using MRI scans of the monkeys’ brains, they observed that activity in the cingulate cortex “reflected whether the internal value representations would be translated into actual behavioral change.”

They showed that, by stimulating the brain region with noninvasive, focused, low-intensity ultrasound, the anterior cingulate cortex was of “causal importance” to this process. Stimulating the brain in this way disrupted the monkeys’ counterfactual thinking.

Fouragnan concludes that brain stimulation using noninvasive, focused, low-intensity ultrasound “has the potential to improve the lives of millions of patients with mental health conditions by stimulating brain tissues with millimeter accuracy.”

Some brain stimulation techniques are already helping people with Parkinson’s disease and depression, but because they are nonsurgical, the methods do not have the level of accuracy achieved in this study, she adds.

It’s still early stages, and the next stage is for further trials to be conducted in humans, but the potential is very exciting.”

Elsa Fouragnan, Ph.D.