Study sheds light on the brain’s “internal clock”

The timekeeper within: New discovery on how the brain judges time.

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The basal ganglia are believed to play a role in decision-making and motor control. The striatum, which serves as these processes’ primary input structure, can be used to derive temporal information on the neural populations’ developing state. It is unclear, nevertheless, whether striatal activity governs the kinematics of overt movement or latent, dynamic decision processes.

The “internal clock” of the brain has been revealed by a group of neuroscientists at the Champalimaud Foundation using temperature manipulation of a particular brain area. This research paves the path for a greater comprehension of how our brains analyze and coordinate actions in addition to time perception.

In recent research from Champalimaud Research’s Learning Lab, which was published in the journal Nature Neuroscience, researchers deliberately sped up or slowed down patterns of neural activity in rats, distorting their perception of time and offering the strongest causal support yet for how the brain’s internal clockwork regulates behavior.

Whether you’re sitting at a stop light or serving a tennis ball, the study specifically focused on this seconds-to-minute timescale at which much of our behavior develops.

Our brains maintain a decentralized and flexible sense of time instead of the precise ticking of a computer’s central clock, which is assumed to be modified by the dynamics of neural networks distributed throughout the brain. According to the “population clock” theory, our brains keep time by depending on regular patterns of activity that develop in neural clusters as we behave.

The study’s senior author Joe Paton likens this to dropping a stone into a pond. “Each time a stone is dropped, it creates ripples that radiate outward on the surface in a repeatable pattern. By examining the patterns and positions of these ripples, one can deduce when and where the stone was dropped into the water”.

“Just as the speed at which the ripples move can vary, the pace at which these activity patterns progress in neural populations can also shift. Our lab was one of the first to demonstrate a tight correlation between how fast or slow these neural ‘ripples’ evolve and time-dependent decisions”.

The researchers trained rats to recognize various time intervals. They discovered that activity in the striatum, a deep brain region, changes in predictable patterns and at varying rates depending on how long an interval of time is reported by an animal. When an interval is said to be shorter, the activity evolves more slowly.

Scientists noted, “However, correlation does not imply causation. We wanted to test whether variability in the speed of striatal population dynamics merely correlates with or directly regulates timing behavior. We needed a way to manipulate these dynamics as animals reported timing judgments experimentally.”

Tiago Monteiro, one of the study’s lead authors, said, “Never throw away old tools. To establish causation, we turned to an old-school technique in the neuroscientist’s toolbox: temperature. The temperature has been used in previous studies to manipulate the temporal dynamics of behaviors, such as bird songs.”

“Cooling a specific brain region slows the song, while warming speeds it up without altering its structure. It’s akin to changing the tempo of a musical piece without affecting the notes themselves. We thought temperature would be ideal as it would allow us to change the speed of neural dynamics without disrupting its pattern.”

They created a special thermoelectric device to focally warm or cool the striatum while recording brain activity to test this technology in rats. Because the rats were anesthetized for these tests, the researchers used optogenetics. This method employs light to trigger particular cells to produce waves of activity in the otherwise dormant striatum, similar to dropping a stone into a pond.

Co-lead author Margarida Pexirra said, “We were careful not to cool the area too much, as it would shut down activity, or warm it too much, risking irreversible damage. We found that indeed cooling dilated the pattern of activity, while warming contracted it, without perturbing the pattern itself.”

Filipe Rodrigues, another lead author in the study, said, “Temperature then gave us a knob with which to stretch or contract neural activity in time, so we applied this manipulation in the context of behavior. We trained animals to report whether the interval between two tones was shorter or longer than 1.5 seconds. When we cooled the striatum, they were likelier to say a given interval was short. When we warmed it, they were likelier to say it was long.”

Surprisingly, although the striatum coordinates motor control, altering its activity patterns doesn’t affect the animals’ movements in the task in a way that corresponds to those changes. Due to this, we began to consider the nature of behavior control more carefully. Even the most basic creatures must overcome two fundamental difficulties when managing mobility.

They must decide between various possible courses of action, such as moving ahead or backward. To ensure that an activity is carried out successfully, they must be able to continuously change and regulate it once they have made their decision. These fundamental issues affect all living things, including people and worms.

The team’s findings show that the striatum is essential for deciding “what” to do and “when.” In contrast, other brain areas handle the second issue, controlling the continuing movement. The team is currently investigating the cerebellum, which contains more than half of the brain’s neurons and is connected to the continuous, moment-by-moment execution of human activities, in a separate study.

The data shows that applying temperature manipulations to the cerebellum, unlike the striatum, does affect continuous movement control.

Paton points out, “You can see this division of labor between the two brain systems in movement disorders like Parkinson’s and cerebellar ataxia.”

The team’s findings may aid in developing novel therapeutic targets for debilitating diseases like Parkinson’s and Huntington’s, which have time-related symptoms and compromised striatum. These diseases include Parkinson’s and Huntington’s. Additionally, the findings may impact algorithmic frameworks used in robotics and learning by emphasizing the striatum’s distinct function in discrete motor control instead of continuous motor control.

Monteiro said, “Ironically, this study was years in the making for a paper about time. But there’s plenty more mystery to unravel. What brain circuits create these timekeeping ripples of activity in the first place? What computations, other than keeping time, might such ripples perform? How do they help us adapt and respond intelligently to our environment? To answer these questions, we will need more of something we’ve been studying…time.”

Journal Reference:

  1. Monteiro, T., Rodrigues, F.S., Pexirra, M. et al. Using temperature to analyze the neural basis of a time-based decision. Nat Neurosci (2023). DOI: 10.1038/s41593-023-01378-5
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