Our decision-making process remains hazy (Image: Jannes Glas/Getty)

In the early 1980s, Benjamin Libet, a neuroscientist at the University of California in San Francisco, used electroencephalography (EEG) to record the brain activity of volunteers who had been told to make a spontaneous movement. With the help of a precise timer that the volunteers were asked to read at the moment they became aware of the urge to act, Libet found there was a 200 millisecond delay, on average, between this urge and the movement itself.

But the EEG recordings also revealed a signal that appeared in the brain even earlier, 550 milliseconds, on average, before the action. Called the readiness potential, this has been interpreted as a blow to free will, as it suggests that the brain prepares to act well before we are conscious of the urge to move.

This conclusion assumes that the readiness potential is the signature of the brain planning and preparing to move. “Even people who have been critical of Libet’s work, by and large, haven’t challenged that assumption,” says Aaron Schurger of the National Institute of Health and Medical Research in Saclay, France.

One attempt to do so came in 2009. Judy Trevena and Jeff Miller of the University of Otago in Dunedin, New Zealand, asked volunteers to decide, after hearing a tone, whether or not to tap on a keyboard. The readiness potential was present regardless of their decision, suggesting that it did not represent the brain preparing to move. Exactly what it did mean, though, still wasn’t clear.

Crossing a threshold

Now, Schurger and colleagues have an explanation. They began by posing a question: how does the brain decide to make a spontaneous movement? They looked to other decision-making scenarios for clues. Previous studies have shown that when we have to make a decision based on visual input, for example, assemblies of neurons start accumulating visual evidence in favour of the various possible outcomes. A decision is triggered when the evidence favouring one particular outcome becomes strong enough to tip its associated assembly of neurons across a threshold.

Schurger’s team hypothesised that something similar happens in the brain during the Libet experiment. Volunteers, however, are specifically asked to ignore any external signals before they make a spontaneous movement, so the signal must be internal.

There are random fluctuations of neural activity in the brain. Schurger’s team reasoned that movement is triggered when this neural noise accumulates and crosses a threshold.

To probe the idea, the team first built a computer model of such a neural accumulator. In the model, each time the neural noise crossed a threshold it signified a decision to move. They found that when they ran the model numerous times and looked at the pattern of the neural noise that led up to the decision it looked like a readiness potential.

Next, the team repeated Libet’s experiment, but this time if, while waiting to act spontaneously, the volunteers heard a click they had to act immediately. The researchers predicted that the fastest response to the click would be seen in those in whom the accumulation of neural noise had neared the threshold – something that would show up in their EEG as a readiness potential.

This is exactly what the team found. In those with slower responses to the click, the readiness potential was absent in the EEG recordings.

Spontaneous brain activity

"Libet argued that our brain has already decided to move well before we have a conscious intention to move," says Schurger. "We argue that what looks like a pre-conscious decision process may not in fact reflect a decision at all. It only looks that way because of the nature of spontaneous brain activity."

So what does this say about free will? “If we are correct, then the Libet experiment does not count as evidence against the possibility of conscious will,” says Schurger.

Cognitive neuroscientist Anil Seth of the University of Sussex in Brighton, UK, is impressed by the work, but also circumspect about what it says about free will. “It’s a more satisfying mechanistic explanation of the readiness potential. But it doesn’t bounce conscious free will suddenly back into the picture,” he says. “Showing that one aspect of the Libet experiment can be open to interpretation does not mean that all arguments against conscious free will need to be ejected.”

According to Seth, when the volunteers in Libet’s experiment said they felt an urge to act, that urge is an experience, similar to an experience of smell or taste. The new model is “opening the door towards a richer understanding of the neural basis of the conscious experience of volition”, he says.

Source: NewScientist

The researchers say understanding this process of chemical signaling may shed light on how the brain reacts to its environment and how current antidepressants work, because in animals these drugs have been shown to increase the number of brain cells. The findings are reported July 29 in the advance online publication of Nature.

“What we learned is that brain stem cells don’t communicate in the official way that neurons do, through synapses or by directly signaling each other,” says Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine’s Institute for Cell Engineering’s Stem Cell Program. “Synapses, like cell phones, allow nerve cells to talk with each other. Stem cells don’t have synapses, but our experiments show they indirectly hear the neurons talking to each other; it’s like listening to someone near you talking on a phone.”

The “indirect talk” that the stem cells detect is comprised of chemical messaging fueled by the output of neurotransmitters that leak from neuronal synapses, the structures at the ends of brain cells that facilitate communication. These neurotransmitters, released from one neuron and detected by a another one, trigger receiving neurons to change their electrical charges, which either causes the neuron to fire off an electrical pulse propagating communication or to settle down, squelching further messages.

To find out which neurotransmitter brain stem cells can detect, the researchers took mouse brain tissue, attached electrodes to the stem cells and measured any change in electrical charge after the addition of certain neurotransmitters. When they treated the stem cells with the neurotransmitter GABA – a known signal-inhibiting product the stem cells’ electrical charges changed, suggesting that the stem cells can detect GABA messages.

To find out what message GABA imparts to brain stem cells, the scientists used a genetic trick to remove the gene for the GABA receptor — the protein on the surface of the cell that detects GABA — only from the brain stem cells. Microscopic observation of brain stem cells lacking the GABA receptor over five days showed these cells replicated themselves, or produced glial cells — support cells for the neurons in the brain. Brain stem cells with their GABA receptors intact appeared to stay the same, not making more cells.

Next, the team treated normal mice with valium, often used as an anti-anxiety drug and known to act like GABA by activating GABA receptors when it comes in contact with them. The scientists checked the mice on the second and seventh day of valium use and counted the number of brain stem cells in untreated mice and mice treated with the GABA activator. They found the treated mice had many more dormant stem cells than the untreated mice.

“Traditionally GABA tells neurons to shut down and not continue to propagate a message to other neurons,” says Song. “In this case the neurotransmitter also shuts off the stem cells and keeps them dormant.”

The brain stem cell population in mice (and other mammals, including humans) is surrounded by as many as 10 different kinds of intermingled neurons, says Song, and any number of these may be keeping stem cells dormant. To find out which neurons control the stem cells, the researchers inserted special light-activating proteins into the neurons that trigger the cells to send an electrical pulse, as well as to release neurotransmitter, when light shines on them. By shining light to activate a specific type of neuron and monitoring the stem cells with an electrode, Song’s team showed that one of the three types of neurons tested transmitted a signal to the stem cells causing a change in electrical charge in the stem cells. The neurons messaging the stem cells are parvalbumin-expressing interneurons.

Finally, to see if this stem cell control mechanism aligns with what an animal may be experiencing, the scientists created stress for normal mice by socially isolating them, and did the same in mice lacking GABA receptors in their brain stem cells. After a week, socially isolated normal mice had an increase in the number of stem cells and glial cells. But the socially isolated mice without GABA receptors did not show increases.

“GABA communication clearly conveys information about what brain cells experience of the outside world, and, in this case, keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up,” says Song.

Source: Johns Hopkins Medicine