Brain zap saps destructive urges

December 19, 2017 by Bruce Goldman, Stanford University Medical Center
Credit: CC0 Public Domain

A characteristic electrical-activity pattern in a key brain region predicts impulsive actions just before they occur. A brief electrical pulse at just the right time can prevent them, Stanford scientists have found.

Stanford University School of Medicine investigators have identified the smoking gun of a "moment of weakness": a signature pattern of electrical activity in a small, deep-brain region just a second or two before a burst of impulsive behavior.

The Stanford scientists discovered similar patterns in that had learned to binge eat and in a human subject anticipating a large cash reward. The researchers also showed, in mice, that supplying a small electrical pulse to the brain region in question, called the , as soon as the electrical signature manifested prevented the mice from overindulging in fatty food, while not affecting their intake of normal food, their social behavior or other physical activity.

The findings were published online Dec.18 in the Proceedings of the National Academies of Sciences.

"We've identified a real-time biomarker for impulsive behavior," said Casey Halpern, MD, assistant professor of neurosurgery and the study's senior author. Postdoctoral scholar Hemmings Wu, Ph.D., and neurosurgery resident Kai Miller, MD, Ph.D., share lead authorship.

Good impulses gone bad

"Impulses are normal and absolutely necessary for survival," Halpern said. "They convert our feelings about what's rewarding into concrete action to obtain food, sex, sleep and defenses against rivals or predators."

But in some contexts, impulsive behavior can be pathological, manifesting as a marked tendency to make poor decisions and act on them. One need look no further than the recent rash of reports of sexual predators perched in powerful positions in Hollywood, the media, finance and politics to see examples of a fundamentally healthy drive—sexual appetite—taken to a pathological level.

The nucleus accumbens is the hub of the brain's reward circuitry, which evolution has engineered to reinforce survival-promoting actions by inducing pleasure in anticipation or performance of those actions. The study's findings offer the promise, Halpern said, of an implantable device that monitors the nucleus accumbens for the telltale signal preceding a burst of impulsivity and immediately delivers a measured dose of electricity. This intervention may prevent impulsive and sometimes life-threatening actions by high-risk people for whom all noninvasive therapies have failed.

The findings could also lead to less invasive methods of countering obesity, substance-abuse disorders, pathological gambling, sexual addiction or intermittent explosive disorder, a psychiatric condition marked by impromptu outbursts of inappropriate ferocity.

"Imagine if you could predict and prevent a suicide attempt, a heroin injection, a burst of binge eating or alcohol intake, or a sudden bout of uncontrolled rage," said Halpern.

Clinically, Halpern focuses on deep-brain stimulation, whereby devices deliver electrical pulses to targeted in which they've been implanted. DBS is now approved by the Food and Drug Administration for treating symptoms of Parkinson's disease and essential tremor, and is currently in clinical trials for depression, obsessive-compulsive disorder and multiple other disorders of the brain.

But the tens of thousands of DBS devices in current use are inflexible in the timing, duration and intensity of the pulses they deliver; they simply fire away on a preprogrammed basis, 24/7. New-generation devices can respond to feedback from the brain region they target, or even a distant one, so pulses get delivered only when necessary and at appropriate intensities. These so-called responsive neurostimulation devices have so far been approved for partial-onset epilepsy. Because they fire only after sensing specific electrical-activity signatures, they may actually deliver as little as five minutes per day of total stimulation, which neuroscientists such as Halpern view as greatly advantageous from the standpoint of avoiding side effects and optimizing the behavioral specificity of the treatment.

"There's no available responsive neurostimulation intervention for dangerous yet, because until now no one's been able to document a characteristic signature in the brain that could be used for triggering pulse delivery by the device," he said.

From mouse to man

The Stanford scientists discovered this signature in experiments with mice. Typically, laboratory mice are fed pellets of a standard chow that's nutritious without being highly caloric. In the study, mice were given special high-fat food pellets for one hour every day for 10 days. During that hour, they were allowed to eat as much as they wanted.

The novel food took some getting used to, but by day 10 the mice became habituated to it and pretty much ate it nonstop. The researchers had implanted electrode arrays in the mice's brains in order to monitor electrical activity in the nucleus accumbens, where a pattern of heightened electrical activity—restricted to a particular low-frequency band called delta—emerged immediately prior to binge eating, peaking about one second before a mouse took a bite of the high-fat food pellet. Notably, this uptick didn't occur when that mouse was about to bite into standard lab chow. Nor was it seen in other typically rewarding activities, such as interactions with younger mice.

Halpern and his colleagues then programmed their electrode arrays to deliver 10-second pulses of electrical current—the typical regimen in approved DBS therapies—to the nucleus accumbens whenever the arrays sensed a sizeable increase in delta intensity there. This substantially reduced the mice's high-fat binges. But it didn't affect their social lives, or their general physical behavior.

Further experiments compared responsive neurostimulation to standard DBS, random pulse delivery and manual delivery whenever an experimenter saw a mouse preparing to stuff itself. Both manual and responsive-neurostimulation pulse delivery proved superior to either random or DBS delivery, despite delivering far fewer electrical pulses daily than DBS.

Next, the Stanford researchers took advantage of a rare opportunity to perform a similar experiment on a human subject: a patient with obsessive-compulsive disorder, a condition for which DBS to the nucleus accumbens is in clinical trials. This participant was resistant to all other treatments for his OCD and had opted for surgical implantation of a DBS device.

The investigators received the participant's consent to intervene briefly once electrical leads had been introduced to the participant's nucleus accumbens but prior to their hookup with the DBS pulse generator. In the interim, the participant was asked to perform computerized tasks that generated cash rewards if completed successfully. As with the mice, once the participant got acclimated to the near-certainty of receiving a reward upon completing the task, a receiver to which the implanted electrical leads were temporarily hooked was able to detect the characteristic "high-delta" electrical signature in his nucleus accumbens just before he commenced the tasks.

"The fact that we saw a similar signal prior to two different behaviors, both intended to obtain rewards—food in the case of mice, money in the case of the human subject—to which the individuals had become hypersensitized by their repeated exposure suggests that this signal may be common to many impulsive behaviors, making them amenable to treatment along similar lines," said Halpern.

Unlike newer parts of the brain, such as the cerebral cortex, the more deeply seated reward system's components have largely been conserved among vertebrates. So Halpern thinks the behavior-altering results his team observed in mice are likely to apply to humans, although further study will be needed to confirm these findings in a single human subject.

Halpern, Wu and study co-author Robert Malenka, MD, Ph.D., professor of psychiatry and behavioral sciences, are co-authors of a provisional patent filed by Stanford's Office of Technology Licensing on intellectual property associated with these findings.

Explore further: Binge eating improves with deep brain stimulation surgery

More information: Hemmings Wu et al. Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1712214114

Related Stories

Binge eating improves with deep brain stimulation surgery

June 25, 2012
Deep brain stimulation reduces binge eating in mice, suggesting that this surgery, which is approved for treatment of certain neurologic and psychiatric disorders, may also be an effective therapy for obesity. Presentation ...

Anticipation helps pathological gamblers hold out for larger-but-later rewards

June 5, 2017
Triggering pathological gamblers to envision a future personal experience reduces their preference for an immediate reward over a larger, delayed award, according to a study published in eNeuro.

Binge eating curbed by deep brain stimulation in animal model, study shows

April 24, 2013
(Medical Xpress)—Deep brain stimulation (DBS) in a precise region of the brain appears to reduce caloric intake and prompt weight loss in obese animal models, according to a new study led by researchers at the University ...

Study shows how 'love hormone' oxytocin spurs sociability

September 28, 2017
Why is it so much fun to hang out with our friends? Why are some people so sociable while others are loners or seemingly outright allergic to interactions with others?

Oxytocin turns up the volume of your social environment

September 20, 2017
Before you shop for the "cuddle" hormone oxytocin to relieve stress and enhance your social life, read this: a new study from the University of California, Davis, suggests that sometimes, blocking the action of oxytocin in ...

New study identifies gene that could play key role in depression

July 6, 2017
Globally, depression affects more than 300 million people annually. Nearly 800,000 die from suicide every year—it is the second-leading cause of death among people between the ages of 15 to 29. Beyond that, depression destroys ...

Recommended for you

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

Miles Davis is not Mozart: The brains of jazz and classical pianists work differently

January 16, 2018
Keith Jarret, world-famous jazz pianist, once answered in an interview when asked if he would ever be interested in doing a concert where he would play both jazz and classical music: "No, that's hilarious. [...] It's like ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.