Throughout history, humanity has been fascinated by the concept of time, from Aristotle’s contemplations to Einstein’s theory of relativity. Time is not just a constant entity; it can bend and flex, as observed in the phenomenon of time dilation proposed by the theory of relativity. Interestingly, our perception of time can also be influenced by our neural circuits, causing our subjective experience of time to stretch or compress.
Einstein humorously illustrated this notion by comparing the perceived duration of different experiences. For instance, a minute of pain can feel like an eternity, while an hour spent with a loved one can pass by in an instant.
A recent groundbreaking study conducted by Champalimaud Research’s Learning Lab and published in the journal Nature Neuroscience explored this aspect of time perception. Researchers artificially manipulated patterns of neural activity in rats, leading to altered judgments of time duration. This provided compelling evidence of the brain’s inner clockwork influencing behavior.
Unlike the well-known circadian clocks that regulate our 24-hour biological rhythms and affect our daily lives, the mechanisms behind measuring time on the scale of seconds to minutes remain less understood. The study focused precisely on this time range, which is crucial for much of our everyday behavior, whether it’s waiting at a traffic light or playing a game of tennis.
The population clock hypothesis
Unlike a computer’s precise centralized clock, our brains operate with a decentralized and adaptable sense of time, influenced by dynamic neuronal networks scattered throughout the brain. The “population clock” hypothesis suggests that our brains measure time by observing consistent activity patterns evolving within groups of neurons during various behaviors.
Drawing an analogy, Joe Paton, the study’s senior author, compares this process to dropping a stone into a pond, creating ripples that spread outward in a predictable pattern. Similarly, the brain examines the patterns and positions of neuronal activity to deduce when and where an event occurred.
Just as the speed of ripples in water can vary, the pace at which activity patterns progress in neural populations can also shift. Paton’s team established a strong link between the speed of these neural “ripples” and time-dependent decisions, showcasing a tight correlation.
To delve deeper into the causative relationship, the researchers trained rats to differentiate between different time intervals. They observed that activity in the striatum, a deep brain region, followed predictable patterns that changed at varying speeds. Interestingly, when the animals perceived a given time interval as longer, the neural activity evolved faster, and when they perceived it as shorter, the activity unfolded more slowly.
Nonetheless, establishing a correlation does not prove causation. To address this, the researchers needed to experimentally manipulate the dynamics of the striatal population’s speed while the animals made timing judgments.
Unraveling time with temperature
“With a grin, Tiago Monteiro, one of the study’s lead authors, emphasized the value of retaining old tools. To establish causation, the team turned to a classic technique in the neuroscientist’s arsenal: temperature manipulation.
In previous studies, researchers had successfully used temperature to alter the temporal dynamics of behaviors, like bird song. By cooling a specific brain region, the song’s speed slowed down, while warming it up accelerated the tempo, all without affecting the song’s fundamental structure. Analogously, it’s like changing the tempo of a musical piece without altering the notes themselves. The team believed temperature could be the perfect tool, potentially allowing them to adjust the speed of neural dynamics without disrupting its pattern.
To put this notion to the test in rats, the researchers designed a custom thermoelectric device capable of focal warming or cooling of the striatum while simultaneously recording neural activity. Since the experiments involved anesthetized rats, the researchers used optogenetics, a technique utilizing light to stimulate specific cells, creating waves of activity in the otherwise dormant striatum, akin to dropping a stone into a pond.
Margarida Pexirra, co-lead author, noted their cautious approach to temperature manipulation: avoiding excessive cooling that could shut down activity or excessive warming that might lead to irreversible damage. Their efforts paid off, as cooling dilated the pattern of neural activity, while warming contracted it, all without disturbing the pattern itself.
“Temperature provided us with a knob to stretch or compress neural activity in time, so we decided to apply this manipulation in the context of behavior,” explained Filipe Rodrigues, another lead author.
The researchers trained the rats to determine whether the interval between two tones was shorter or longer than 1.5 seconds. When the striatum was cooled, the rats were more likely to perceive a given interval as short, and when it was warmed, they tended to perceive it as long. For instance, heating up the striatum accelerated striatal population dynamics, resembling the faster movement of a clock’s hands, leading the rats to judge a particular time interval as longer than its actual duration.
Two brain systems for motor control
Paton added a surprising observation that altering the patterns of activity in the striatum, a brain region involved in motor control, did not lead to corresponding changes in the animals’ movements during the task. This raised intriguing questions about the broader nature of behavior control. He highlighted two fundamental challenges faced by even the simplest organisms when it comes to controlling movement.
Firstly, organisms must choose from various potential actions, such as moving forward or backward. Secondly, once an action is selected, they need to continuously adjust and control it to ensure effective execution. These challenges apply across different species, from worms to humans.
The study’s findings suggest that the striatum plays a crucial role in resolving the first challenge—determining “what” to do and “when” to do it—while the second challenge of “how” to control ongoing movement is handled by other brain structures.
The team is now conducting a separate study to investigate the cerebellum, which houses a significant portion of the brain’s neurons and is associated with continuous, moment-to-moment execution of actions. Preliminary data indicates that temperature manipulations in the cerebellum do affect continuous movement control, unlike in the striatum.
Paton points out that this division of labor between the two brain systems is evident in movement disorders like Parkinson’s and cerebellar ataxia. In Parkinson’s, which affects the striatum, patients may struggle with self-initiating motor plans, like walking, but providing sensory cues can facilitate movement. These cues likely engage other brain regions, such as the intact cerebellum and cortex, which can effectively manage continuous movement. On the other hand, individuals with cerebellar damage face challenges in executing smooth and coordinated movements, but their initiation or transition between movements might not be as severely affected.
Implications and future directions
The team’s groundbreaking findings, shedding light on the causal relationship between neural activity and timing function, hold great promise for the development of innovative therapeutic targets to address debilitating diseases like Parkinson’s and Huntington’s. These conditions involve time-related symptoms and a compromised striatum. With a deeper understanding of how neural activity influences timing, researchers may devise more effective treatments for these conditions.
Moreover, the study’s insights into the specific role of the striatum in discrete motor control, as opposed to continuous control, could have implications beyond medical applications. It may impact algorithmic frameworks used in robotics and learning, enhancing our understanding of how machines and artificial intelligence can be programmed to execute tasks with better precision and timing.
Despite the years of effort invested in this study, there remain fascinating mysteries to unravel. The researchers are eager to explore the brain circuits responsible for generating these timekeeping ripples of activity. They also seek to understand the additional computations, beyond timekeeping, that these neural ripples might perform. Furthermore, investigating how these mechanisms enable us to adapt and intelligently respond to our environment poses an exciting avenue for future research. As Tiago Monteiro humorously points out, for a study centered on time, it seems that they will need more time to answer these intriguing questions.
Source: Champalimaud Centre for the Unknown