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Researchers Partially Control a Memory

March 28, 2012 Leave a comment

Scripps Research Institute Team Wrests Partial Control of a Memory

The work advances understanding of how memories form and offers new insight into disorders such as schizophrenia and post traumatic stress disorder.

Scripps Research Institute scientists and their colleagues have successfully harnessed neurons in mouse brains, allowing them to at least partially control a specific memory. Though just an initial step, the researchers hope such work will eventually lead to better understanding of how memories form in the brain, and possibly even to ways to weaken harmful thoughts for those with conditions such as schizophrenia and post traumatic stress disorder.

The results are reported in the March 23, 2012 issue of the journal Science.

Researchers have known for decades that stimulating various regions of the brain can trigger behaviors and even memories. But understanding the way these brain functions develop and occur normally—effectively how we become who we are—has been a much more complex goal.

“The question we’re ultimately interested in is: How does the activity of the brain represent the world?” said Scripps Research neuroscientist Mark Mayford, who led the new study. “Understanding all this will help us understand what goes wrong in situations where you have inappropriate perceptions. It can also tell us where the brain changes with learning.”

On-Off Switches and a Hybrid Memory

As a first step toward that end, the team set out to manipulate specific memories by inserting two genes into mice. One gene produces receptors that researchers can chemically trigger to activate a neuron. They tied this gene to a natural gene that turns on only in active neurons, such as those involved in a particular memory as it forms, or as the memory is recalled. In other words, this technique allows the researchers to install on-off switches on only the neurons involved in the formation of specific memories.

For the study’s main experiment, the team triggered the “on” switch in neurons active as mice were learning about a new environment, Box A, with distinct colors, smells and textures.

Next the team placed the mice in a second distinct environment—Box B—after giving them the chemical that would turn on the neurons associated with the memory for Box A. The researchers found the mice behaved as if they were forming a sort of hybrid memory that was part Box A and part Box B. The chemical switch needed to be turned on while the mice were in Box B for them to demonstrate signs of recognition. Alone neither being in Box B nor the chemical switch was effective in producing memory recall.

“We know from studies in both animals and humans that memories are not formed in isolation but are built up over years incorporating previously learned information,” Mayford said. “This study suggests that one way the brain performs this feat is to use the activity pattern of nerve cells from old memories and merge this with the activity produced during a new learning session.”

Future Manipulation of the Past

The team is now making progress toward more precise control that will allow the scientists to turn one memory on and off at will so effectively that a mouse will in fact perceive itself to be in Box A when it’s in Box B.

Once the processes are better understood, Mayford has ideas about how researchers might eventually target the perception process through drug treatment to deal with certain mental diseases such as schizophrenia and post traumatic stress disorder. With such problems, patients’ brains are producing false perceptions or disabling fears. But drug treatments might target the neurons involved when a patient thinks about such fear, to turn off the neurons involved and interfere with the disruptive thought patterns.

Notes about this memory research article

In addition to Mayford, other authors of the paper, “Generation of a Synthetic Memory Trace,” are Aleena Garner, Sang Youl Hwang, and Karsten Baumgaertel from Scripps Research, David Rowland and Cliff Kentros from the University of Oregon, Eugene, and Bryan Roth from the University of North Carolina (UNC), Chapel Hill.

This work is supported by the National Institute of Mental Health, the National Institute on Drug Abuse, the California Institute for Regenerative Medicine, and the Michael Hooker Distinguished Chair in Pharmacology at UNC.

Source:

Source: The Scripps Research Institute press release

Original Research: Abstract for “Generation of a Synthetic Memory Trace” by Aleena R. Garner, David C. Rowland, Sang Youl Hwang, Karsten Baumgaertel, Bryan L. Roth, Cliff Kentros & Mark Mayford in Science

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Human Thought Can Voluntarily Control Neurons in Brain


Neuroscience research involving epileptic patients with brain electrodes surgically implanted in their medial temporal lobes shows that patients learned to consciously control individual neurons deep in the brain with thoughts.

Subjects learned to control mouse cursors, play video games and alter focus of digital images with their thoughts. The patients were each using brain computer interfaces, deep brain electrodes and software designed for the research.

Controlling Individual Cortical Nerve Cells by Human Thought

Five years ago, neuroscientist Christof Koch of the California Institute of Technology (Caltech), neurosurgeon Itzhak Fried of UCLA, and their colleagues discovered that a single neuron in the human brain can function much like a sophisticated computer and recognize people, landmarks, and objects, suggesting that a consistent and explicit code may help transform complex visual representations into long-term and more abstract memories.

Now Koch and Fried, along with former Caltech graduate student and current postdoctoral fellow Moran Cerf, have found that individuals can exert conscious control over the firing of these single neurons—despite the neurons’ location in an area of the brain previously thought inaccessible to conscious control—and, in doing so, manipulate the behavior of an image on a computer screen.

The work, which appears in a paper in the October 28 issue of the journal Nature, shows that “individuals can rapidly, consciously, and voluntarily control neurons deep inside their head,” says Koch, the Lois and Victor Troendle Professor of Cognitive and Behavioral Biology and professor of computation and neural systems at Caltech.

The study was conducted on 12 epilepsy patients at the David Geffen School of Medicine at UCLA, where Fried directs the Epilepsy Surgery Program. All of the patients suffered from seizures that could not be controlled by medication. To help localize where their seizures were originating in preparation for possible later surgery, the patients were surgically implanted with electrodes deep within the centers of their brains. Cerf used these electrodes to record the activity, as indicated by spikes on a computer screen, of individual neurons in parts of the medial temporal lobe—a brain region that plays a major role in human memory and emotion.

Prior to recording the activity of the neurons, Cerf interviewed each of the patients to learn about their interests. “I wanted to see what they like—say, the band Guns N’ Roses, the TV show House, and the Red Sox,” he says. Using that information, he created for each patient a data set of around 100 images reflecting the things he or she cares about. The patients then viewed those images, one after another, as Cerf monitored their brain activity to look for the targeted firing of single neurons. “Of 100 pictures, maybe 10 will have a strong correlation to a neuron,” he says. “Those images might represent cached memories—things the patient has recently seen.”

The four most strongly responding neurons, representing four different images, were selected for further investigation. “The goal was to get patients to control things with their minds,” Cerf says. By thinking about the individual images—a picture of Marilyn Monroe, for example—the patients triggered the activity of their corresponding neurons, which was translated first into the movement of a cursor on a computer screen. In this way, patients trained themselves to move that cursor up and down, or even play a computer game.

But, says Cerf, “we wanted to take it one step further than just brain–machine interfaces and tap into the competition for attention between thoughts that race through our mind.”

To do that, the team arranged for a situation in which two concepts competed for dominance in the mind of the patient. “We had patients sit in front of a blank screen and asked them to think of one of the target images,” Cerf explains. As they thought of the image, and the related neuron fired, “we made the image appear on the screen,” he says. That image is the “target.” Then one of the other three images is introduced, to serve as the “distractor.”

“The patient starts with a 50/50 image, a hybrid, representing the ‘marriage’ of the two images,” Cerf says, and then has to make the target image fade in—just using his or her mind—and the distractor fade out. During the tests, the patients came up with their own personal strategies for making the right images appear; some simply thought of the picture, while others repeated the name of the image out loud or focused their gaze on a particular aspect of the image. Regardless of their tactics, the subjects quickly got the hang of the task, and they were successful in around 70 percent of trials.

“The patients clearly found this task to be incredibly fun as they started to feel that they control things in the environment purely with their thought,” says Cerf. “They were highly enthusiastic to try new things and see the boundaries of ‘thoughts’ that still allow them to activate things in the environment.”

Notably, even in cases where the patients were on the verge of failure—with, say, the distractor image representing 90 percent of the composite picture, so that it was essentially all the patients saw—”they were able to pull it back,” Cerf says. Imagine, for example, that the target image is Bill Clinton and the distractor George Bush. When the patient is “failing” the task, the George Bush image will dominate. “The patient will see George Bush, but they’re supposed to be thinking about Bill Clinton. So they shut off Bush—somehow figuring out how to control the flow of that information in their brain—and make other information appear. The imagery in their brain,” he says, “is stronger than the hybrid image on the screen.”

According to Koch, what is most exciting “is the discovery that the part of the brain that stores the instruction ‘think of Clinton’ reaches into the medial temporal lobe and excites the set of neurons responding to Clinton, simultaneously suppressing the population of neurons representing Bush, while leaving the vast majority of cells representing other concepts or familiar person untouched.”

The work in the paper, “On-line voluntary control of human temporal lobe neurons,” is part of a decade-long collaboration between the Fried and Koch groups, funded by the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, the G. Harold & Leila Y. Mathers Charitable Foundation, and Korea’s World Class University program.

Source: California Institute of Technology (Caltech)

Research suggests humans can learn to consciously control individual neurons in the brain. Image credit: Moran Cerf and Maria Moon/Caltech