Scientists Discover How to Manipulate the Brain’s Perception of Time
The Learning Lab at the Champalimaud Institute has discovered a way to manipulate the brain’s perception of time by controlling neural activity in rats. The research, which could potentially be applied to the treatment of diseases such as Parkinson’s and Huntington’s disease, could also have implications for the fields of robotics and learning algorithms.
From Aristotle’s musings on the nature of time to Einstein’s theory of relativity, humanity has long pondered how to perceive and understand time. The theory of relativity postulates that time can stretch or shrink. Just as the universe warps time, our neural circuits can stretch and contract our subjective experience of time. As Einstein famously said, “If you put your hand on a hot stove for a minute, it feels like an hour. If you sit with a pretty girl for an hour, it feels like a minute.”
In a new study from the Learning Lab at the Champalimaud Institute, published in Nature Neuroscience, scientists artificially slowed or sped up patterns of neural activity in rats.
Little is known about how the body measures time in seconds to minutes, as opposed to the more familiar circadian clock that governs our 24-hour biological rhythms and shapes our daily lives, from sleep-wake cycles to metabolism. This study focused precisely on this seconds-to-minutes timescale in which many of our actions unfold, whether we are waiting at a traffic light or serving a tennis ball.
Unlike the computer’s centralized clock that precisely ticks, our brains maintain a distributed and flexible sense of time. In this “collective clock” hypothesis, our brains rely on consistent patterns of activity evolving in groups of neurons during behavior to keep time.
Joe Paton, the senior author of the study, compares this to dropping a stone into a pond. Each time a stone is dropped, ripples form and radiate across the surface of the pond. By studying the pattern and location of these ripples, we can deduce when and where the stone was dropped.”
Scientists Discover How to Manipulate the Brain’s Perception of Time
“Just as the speed at which ripples move can vary, the pace at which these patterns of activity in neural populations progress can also vary. Our laboratory was one of the first to demonstrate a close correlation between the speed or slowness of the progress of this neural “ripple” and time-dependent judgments.”
The researchers trained rats to distinguish between different time intervals. They found that activity in the striatum, a deep brain region, follows predictable patterns that vary at different rates. If an animal reports a longer time interval, activity evolves more quickly; if it reports a shorter interval, activity evolves more slowly.
However, correlation does not imply causation. We wanted to test whether “variations in the speed of striatal population dynamics simply correlate with timing behavior, or whether they directly control timing behavior. To do so, we needed a way to experimentally manipulate these dynamics as animals report their timing decisions.”
Unraveling Time with Temperature
Tiago Monteiro, one of the lead authors of the study, smiles, “Never throw away an old tool. To uncover causality, the team turned to an old-fashioned method in the neuroscientist’s toolbox: temperature. Temperature has been used in previous studies to manipulate the temporal dynamics of behaviors like birdsong. Cooling certain areas of the brain slows down the chirping and warming them up speeds up the chirping. This is like changing the tempo of a piece of music without affecting the notes themselves. We thought temperature was ideal because it could potentially change that speed without disrupting the pattern of neural dynamics,” he said.
To test this tool in rats, they developed a custom thermoelectric device to locally warm or cool the striatum while simultaneously recording neural activity. In this experiment, the rats were anesthetized, so the researchers used optogenetics (a technique that uses light to stimulate specific cells) to generate waves of activity in the dormant striatum, like dropping a stone in a pond. Co-author Margarida Peixilla says, “We were careful not to cool the area too much, because if you cool it too much, it stops working, and if you warm it too much, you risk irreversible damage. As a result, we found that cooling the area caused the activity pattern to expand and warming it caused it to contract.
So we applied this manipulation to behavior,” says Filipe Rodriguez, the study’s other lead author. We trained the animals to report whether the interval between two tones was shorter or longer than one. 5 seconds. When the striatum was cooled, there was a stronger tendency to respond that an interval was short. When warmed, they were more likely to respond that it was long. For example, warming the striatum accelerated the collective dynamics of the striatum, similar to the acceleration of the movement of the hands of a clock, causing the rats to judge a given time interval to be longer than it actually was.
Two Brain Systems for Motor Control
Paton added, “Surprisingly, even though the striatum is responsible for motor control, slowing or speeding up the striatal activity pattern does not slow or speed up the animal’s movements in the task.” This leads us to think more deeply about the nature of behavioral control. Even the simplest organisms face two fundamental challenges in controlling movement. First, one must choose among different potential behaviors. Second, once a behavior is selected, it must be able to be continuously adjusted and controlled so that it is effectively executed. These basic problems apply to all kinds of organisms, from worms to humans.”
The team’s findings show that while the striatum is critical to the first task – determining “what” to do and “when” to do it – the second task – “how” to control continuous movement – is left to other brain structures. In another study, the team is now investigating the cerebellum, which houses more than half of the brain’s neurons and is associated with the continuous and instantaneous execution of our actions. Paton reveals, “Interestingly, our preliminary data show that, unlike the striatum, temperature manipulation of the cerebellum affects continuous motor control.”
As Paton points out, “In movement disorders such as Parkinson’s disease and cerebellar ataxia, we see this division of labor between the two brain systems.”
Parkinson’s disease, which involves the striatum, often interferes with a patient’s ability to plan his or her own locomotion, such as walking. However, giving sensory cues, such as lines of tape on the ground, can facilitate walking. Such cues are likely to involve other brain regions, such as the cerebellum and cerebral cortex, which are still intact and can effectively manage continuous movement. In contrast, patients with cerebellar damage may struggle to perform smooth, coordinated movements, but not necessarily to initiate or switch movements. By gaining new insights into the causal relationship between neural activity and timing function, the research team may advance the development of new therapeutic targets for debilitating diseases such as Parkinson’s disease and Huntington’s disease, which involve time-related symptoms and striatal dysfunction. In addition, the identification of the striatum’s specific role in discrete, as opposed to continuous, motor control may also influence the algorithmic framework used in robotics and learning.
Says Monteiro, “Ironically, for a paper on time, this research has been going on for years.” But there are still many mysteries. To begin with, what kind of brain circuitry produces these ripples of activity? What calculations do these ripples perform besides keeping time? How do they help us adapt and respond intelligently to our environment? To answer these questions, we will need more of what we have been studying: time.”
Source: Scientists Discover How to Manipulate the Brain’s Perception of Time
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