We know that the cerebellum plays an important role in motor control. Scientists have long thought that this was its sole function. In the mid-1980s, it began to be suspected that the cerebellum also contributed to certain higher cognitive functions. Several anatomical and clinical studies have since confirmed this hypothesis, but these contributions remained unclear. A study recently published in Nature Communications sheds light on the role of the cerebellum in non-motor learning.
The cerebellum is a brain region located at the back of the skull, below the cerebral hemispheres. It plays a major role in the control of motor function. Indeed, it is essential for balance, coordination and precision of movements. But its function does not stop there. “ Anatomical tracing studies have shown that the cerebellum sends signals not only to motor areas, but also to non-motor areas of the cerebral cortex », Note the authors of the study. Neuroimaging data has confirmed that the cerebellum is also involved in various cognitive processes, including executive function, working memory, language, emotions, and more. However, its contributions to non-motor functions remain poorly understood. Neuroscientists from the University of Pittsburgh and Columbia University conducted a series of experiments on monkeys to try to elucidate these brain mechanisms.
A brain region that uses error-related information
The cerebellum represents approximately 10% of the brain mass. However, it contains almost 80% of the brain’s neurons! Two types of neurons play a predominant role: Purkinje cells (or P cells) and granule cells. P cells are among the largest neurons in the human brain. They effectively control and coordinate the body’s motor movements by releasing a neurotransmitter that inhibits certain neurons.
The cerebellum is essential to the learning process that allows sensory cues to be associated with specific actions. It relies on these sensory cues to refine motor activity. To do this, it constantly “monitors” our environment, as well as the results of the movements we make. This allows us, for example, to fill a glass correctly, to lift an object with the necessary force, etc.
The cerebellum essentially learns from our mistakes. It uses information about these errors to adjust the strength of brain connections. So, over time, our behavioral responses are increasingly adapted to the signals we perceive. Thus, our motor actions are shaped by our past experiences.
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“ As the cerebellum uses error information to gradually refine movement, another hypothesis has been that it likely contributes to cognitive functions in the same way », Explains Professor Andreea Bostan, co-author of the study.
To test this hypothesis, Bostan and his colleagues trained monkeys to move their left or right hand depending on the image they saw on a screen. If they acted correctly, they were rewarded with a sip of liquid. The goal was for them to associate specific visual cues with the appropriate movement to obtain the reward.
An undeniable role in the learning of visuomotor associations
In previous research, part of the team showed that in the posterior lateral region of the cerebellum, P cell activity changes to reflect the process of learning visuomotor associations depending on reward outcomes.
In this study, two monkeys learned to associate a visual symbol with a movement of the left hand, then another symbol with a movement of the right hand. The researchers reported that P cells collectively retained memory of the most recent decision for the duration of the trial. As the monkeys learned the association, the magnitude of the reward-related error signal approached zero. The posterolateral cerebellum therefore seemed to participate in the learning of new visuomotor associations.
a) Diagram of the experimental setup. b) Representative session, with approximately 30 trials of the overtraining task (left) and 100 trials of the learning task (right). Credits: Sendhilnathan et al., Nature Communications (2024)
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The new study aimed to test whether or not this brain region contributes to learning. The team used a library of 16 pairs of symbols with varying levels of complexity and different levels of similarity between the symbols in each pair. During each session, after the monkeys had completed approximately 30 trials with familiar symbols (overtraining), the researchers presented them with a new pair of symbols randomly chosen from the library.
Before performing these tasks, the monkeys received either a placebo or a drug that temporarily blocked activity in the posterior lateral cerebellum. When presented with a symbol that they had already learned to associate with a certain movement, the primates performed the task correctly. Those who received the placebo were able to learn a new visuomotor association after 50 to 70 trials. In contrast, the monkeys on the blocking agent had difficulty learning even the association that presented the least difficulty in acquisition.
An explanation for the symptoms observed in cerebellar disorders
“ LWhen you inactivate this cerebellar region, you hinder them new learning. It’s much slower, it happens on many more tries, and the performance doesn’t reach the same level », Summarizes Professor Bostan. She adds that this is a concrete example of the cerebellum using reward information to shape cognitive function in primates.
f) Performances monkeys for each session during a news learning task inif they receive the placebo product. g) Same as f, but after injection of muscimol, causing theinactivation of cerebellum posterolateral. Credits: Sendhilnathan et al., Nature Communications (2024)
Inactivation of the posterolateral cerebellum, however, did not prevent the monkeys from successfully making the associations acquired during overtraining. “ This implies that although the posterolateral cerebellar cortex is essential for learning, consolidation lies elsewhere », note the researchers. It also did not affect the overall motor kinematics of the hand movement. The monkeys performed the task with “well-stereotyped” hand movements, both during overtraining and during learning.
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It remained to be verified whether the effect of inactivation was specific to the posterolateral cerebellum. The researchers therefore deactivated more anterior parts of the monkeys’ cerebellum in the same way. This had no effect on their ability to learn new visuomotor associations.
These results suggest that cerebellar circuits may implement functionally distinct computations to enable flexible cognitive learning and behavior. “ Our research provides clear evidence that the cerebellum is not only important for learning to perform skillful actions, but also for knowing which actions are most useful in certain situations. This helps explain some non-motor difficulties observed in people with cerebellar disorders », concludes the neuroscientist.
