How our brain measures time

sense of time

How do the rat and human brains measure time intervals? © Champalimaud Center for the Unknown

Depending on how we fill our time, we perceive it differently: sometimes hours fly by, sometimes minutes feel like hours. But if we consciously focus on it, we can estimate small timescales in the range of seconds to minutes quite accurately. How does our brain do it? A study on rats now provides an indication: If the researchers manipulated the neuronal activity in the striatum, a region of the cerebrum, the rodents' perception of time shifted. The speed of their movements, on the other hand, remained unchanged. The findings could also contribute to the understanding of diseases such as Parkinson's.

Our brain measures time on different scales. The best known of our internal clocks controls our daily rhythm and determines when we get tired, when we wake up and how our metabolism adapts to the time of day. Less research is how our brain estimates smaller time scales from seconds to minutes. One hypothesis is that it relies on regular activity patterns of certain groups of nerve cells, like a clock ticking. But unlike a clock, such nerve cells could sometimes "tick" faster and sometimes slower and thus shift the perception of time. So far, however, it has been difficult to test this hypothesis experimentally.

Neural waves for timekeeping

Now, a team led by Tiago Monteiro from the Champalimaud Foundation in Lisbon has shown in rats that the brain actually relies on neuronal activity in a brain region called the striatum when estimating small time scales. Monteiro's colleague Joseph Paton compares the pattern of this neural activity to a stone falling into water: "The stone creates waves that spread out on the surface in a repeatable pattern. By examining the patterns and positions of these waves, you can deduce when and where the stone fell into the water,” he explains. "Just as the speed at which the waves move can vary, so can the pace at which these patterns of activity progress in neuronal populations."

To prove that the speed of these neural "waves" is actually related to time-dependent decisions, the researchers trained rats to distinguish between different time intervals. If the thirsty rats waited a set time after a signal, they were rewarded with a drop of water. Depending on the signal, they had to estimate whether a period of time was longer or shorter than 1.5 seconds. Meanwhile, the researchers measured activity in the animals' striatum, a part of the basal ganglia in the cerebrum involved in motor control that has previously been linked to time-dependent decisions.

When the internal clock ticks faster or slower

And indeed: If the rats estimated a certain time interval longer, faster neuronal activity was observed in the striatum, if they estimated it shorter, slower activity. Next, the team tested whether this correlation is based on a causal connection. "To do this, we needed a way to experimentally manipulate these dynamics while the animals were making time estimates," explains Monteiro. "We used temperature to change the rate of neuronal dynamics without disturbing the pattern." The team implanted a small thermoelectric device into the trained rats that heated or cooled the striatum at the push of a button.

First measurements on the still anesthetized rats showed that the speed of the neuronal waves actually increased when heated and slowed down when cooled. "The temperature thus gave us a switch with which we could stretch or compress the neuronal activity over time," says Monteiro's colleague Filipe Rodrigues. "We used this manipulation together with the behavioral experiment." The result: "When we cooled the striatum, the rats estimated a time interval to be shorter. If we warmed it, they kept it longer.” The faster activity in the warmed striatum acted like a clock hand ticking faster, suggesting that more time had passed.

Initiate and control movements

While the animals' estimation of time varied, the speed of their movements remained constant. "This got us thinking about the nature of behavioral control in general," says Paton. “Even the simplest organisms face two fundamental challenges in controlling movement. First, they have to choose between different possible actions - for example, in which direction they want to move. Second, once they've decided on an action, they need to be able to continuously adjust and control it to ensure it's being carried out effectively.” The striatum is only involved in the first part, the results suggest—the decision what and when to do. The ongoing control of movement, on the other hand, is left to other brain structures.

In another experiment, the team therefore manipulated the temperature of the cerebellum, which is also involved in controlling movement. Here, the temperature changes ensured that the speed of movement also changed. "This division of labor between the two brain systems is relevant in movement disorders such as Parkinson's," says Paton. In Parkinson's disease, the ability to initiate movements is impaired, but not to execute them. The results of our inner timekeeper could also help to better understand such diseases. In future studies, the team also wants to find out how the circuits in the brain generate the timekeeping waves and how they help us respond to our environment.

Source: Tiago Monteiro (Champalimaud Foundation, Lisbon, Portugal) et al., Nature Neuroscience, doi: 10.1038/s41593-023-01378-5

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