Written by Brett Weiss
February 2019
Until recently, neuroscientists have always talked about motor function and coordination of the body when describing the roles of the cerebellum in human physiology. New studies, though, have revealed potential roles of the cerebellum in learning, socialization, speech fluency, timing, and theory of mind. Moreover, research on therapies for diseases such as epilepsy, autism spectrum disorder, Parkinson’s disease, and schizophrenia have revealed possible methods whereby stimulation of the cerebellum may alleviate symptoms related to cognition and behavior. With 69 billion neurons (compared to the 16 billion neurons of the cerebral cortex), scientists have begun to pose new questions about the function of this brain structure (Vandervert, 2016). Exciting, paradigm-shifting discoveries about this region of the brain lay on the not-too-distant horizon. Some of the discoveries have already begun to take form.
The nervous system makes predictions and validates those predictions against information from the senses, a key function of the nervous system. Growing evidence shows that the nervous system relies on prediction errors, differences in predicted and actual information, in making behavioral judgments. Researchers have viewed the cerebellum in predicting upcoming movements and processing feedback from motor errors. Motor learning experiments, though, have shown that cognition (thought processes outside the motor domain) contributes to motor adaptation that involves the cerebellum (Popa and Ebner, 2018). To what extent does cognition play a role in cerebellar processing?
Some researchers have postulated that cerebellar processing and cognition not only operate in the motor domain but operate in social domains as well. Clausi et al (2018) has made claims that the cerebellum is involved in generating theory of mind, attributing mental states like emotion, intentions, and beliefs to others. The group studied patients with degenerative cerebellar atrophy to find out how the patients performed in tests measuring ability to form theory of mind computations along with other social cognitive tasks compared to healthy neurotypicals. The social cognition tasks that the group used in the study measured immediate responses to emotional stimuli (i.e. perceived feelings when looking at a crying, laughing, or fearful face) and more reflective and thoughtful mental representations based on context and perspective taking (i.e. understanding why a person is crying, laughing, or fearful) for prediction of future social behavior. In both of these domains, patients with degenerative cerebellar atrophy displayed alterations compared to healthy neurotypicals. For instance, researchers found impairments in patients for social “faux pas” stories. In these stories, the patients had to judge when an actor made an inappropriate remark or behaved inappropriately and also had to judge the consequences of the actor’s behavior. In contrast, when patterns of the stories needed only minor prediction levels and error monitoring, the patients showed good performance (Clausi et al., 2018). This study demonstrates that abnormalities in cerebellar function may affect thought processes in social contexts, thought processes seemingly unrelated to motor behavior.
Studies have also indicated that the cerebellum forms connections in the brain with non-motor areas of the frontal cortex, a region toward the front of the brain. Patients with schizophrenia exhibit symptoms associated with frontal cortex dysfunction, including abnormalities in memory for past events, working memory (recent memories held online in the brain), attention, reasoning, and timing. Stimulation with theta frequency bursts to the cerebellum has shown to relieve cognitive symptoms associated with the frontal cortex in treatment-resistant schizophrenia patients (Parker et al., 2014). Parker et al. (2017) showed that stimulation of the cerebellum with delta-frequency (1-4 Hz or 1-4 cycles per second) in rats rescues timing performance and frontal cortex activity. The study went on to propose the use of delta frequency transcranial magnetic stimulation or optogenetics as possible therapeutic strategies for alleviating thought and behavior impairments in patients with schizophrenia (Parker et al, 2018). Transcranial magnetic stimulation is a non-invasive treatment option but would be non-specific in activating neurons that do not connect to the frontal cortex. Optogenetics would activate specific sets of neurons, but a light-activated receptor, channelrhodopsin, would have to be incorporated into neurons in a human. A light that could activate the channelrhodopsin would also have to be surgically implanted into the brain for cerebellar activation.
In patients with schizophrenia, abnormal levels of dopamine persist in the frontal cortex. Low levels of dopamine are thought to facilitate negative symptoms– lack of volition and motivation, emotional blunting, and lack of enjoyment of activities. Higher levels of dopamine are thought to facilitate positive symptoms– delusions and hallucinations. Delta frequency stimulation of the cerebellum may normalize dopamine levels in the frontal cortex through direct or indirect connections between the cerebellum and the frontal cortex (Parker et al., 2017).
Recent research provides evidence that the cerebellum plays roles in brain processes far more extensive than traditional views propose. From predicting through social and motor interactions to generating theory of mind of other actors, it seems highly unlikely that one may restrict roles of the cerebellum to motor behavior. The connections of the cerebellum to other regions of the brain like the frontal cortex may give physicians ways to stimulate the cerebellum for therapeutic treatments of patients with different diseases, including schizophrenia.
References
1. Clausi S, Olivito G, Lupo M, Siciliano L, Bozzali M, and Leggio M (2019). “The Cerebellar Predictions for Social Interactions: Theory of Mind Abilities in Patients with Degenerative Cerebellar Atrophy.” Front Cell Neurosci. 12(510): 1-16.
2. Parker KL, Kim Y, Nessler AJ, Chen K-H, Muller-Ewald VA, Andreasen NC, and Narayanan NS (2017). “Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction.” Mol Psychiatry. 22(5): 647-655.
3. Parker KL, Narayanan NS, and Andreasen NC (2014). “The therapeutic potential of the cerebellum in schizophrenia.” Front Mol Neurosci. 8(163): 1-11.
4. Popa LS and Ebner TJ (2019). “Cerebellum, Predictions and Errors.” Front Cell Neurosci. 12(524): 1-13.
5. Vandervert L (2016). “The prominent role of the cerebellum in the learning, origin and advancement of culture.” Cerebellum and Ataxias. 3(10): 1-13.