Cerebellum and social development

Many of these observations come from the following paper: Olson et al. 2023

• End of the first trimester: deep cerebellar nuclei form (Amore et al. 2021)
• During second trimester: the granular layers and the vermis form (Bromley et al. 1994)
• During the third trimester: cerebellum volume begins to increase exponentially and axonal connections are formed with the rest of the CNS (Pierson and Al Sufiani, 2016)
• Rapid cerebellar growth presents a five-fold increase in volume - 3rd trimester is therefore a critical period in cerebellum development (Limperopoulos et al. 2005A; 2005B; Volpe, 2009b)
• Once the cerebellum is fully formed, it has approximately five times more neurons than the cerebrum (Herculano-Houzel, 2009).
• Cerebellar injury and volume loss is observed in about 20% of infants born before 32 weeks, with incidence increasing in those born before 28 weeks (steggerda et al. 2009)
• Cerebellar underdevelopment at this point in life is associated with a spectrum of severity, with the most severely affected children exhibiting cerebral palsy, epilepsy, intellectual disabilities, and ASD.
• Premature children with damage to the vermis accounted for majority of those with social challenges (Limperopoulos et al. 2007) 70% of all brain tumors in children are posterior fossa tumors. After resection, approximately 25% develop posterior fossa syndrome which is defined as temporary mutism lasting no more than 6 months as well as extreme emotional lability and changes in social behavior (see Riva and Giorgi 2000 paper for case studies of 6 children who underwent surgical ablation of the right vermis to treat posterior fossa tumors).
• Was previously believed that posterior fossa syndrome was caused by damage to the vermis - this view has now been supplanted by the idea that the pathophysiology is due to the cerebello-thalamo-cortical white matter tract.
• While this view would predict that damage anywhere along the pathway would result in core symptoms of posterior fossa syndrome, in practice, the constellation of deficits observed in posterior fossa syndrome are most common after damage to regions encompassing the start point of the CTC tract: dentate nucleus of the cerebellum or cerebellar peduncles.
• Schreiber et al., (2017) tested the 5-year cognitive outcomes of children who had posterior fossa syndrome compared to children with similar tumor resections that did not result in the same disorder. They found that the posterior fossa group exhibited IQ, working memory, speed of processing, and general attention functions that were more than 1 standard deviation below the mean and that there was almost no recovery of function over the 5-years post-surgery.
• Why are changes in social behavior mild during adulthood?
  • CCAS in adults: deficits in four key areas of cognition - spatial processing, executive functioning, linguistic abilities, personality changes - social consequences of CCAS arise after damage to the posterior lobe, especially when the vermis is damaged (Schmahmann and Sherman, 1998).
  • Disorder remains controversial because because it is only rarely observed in the clinic. Consequences of cerebellar damage on observable social behavior in adults are described as rare (Branch & Coslett, 2022), transient (Schmahmann & Sherman, 1998) or mild (Wang et al. 2014) - especially when contrasted to the changes in social compartment observed after lesions to orbitofrontal cortex (Schneider and Koenigs, 2017).
  • The point: adult-onset cerebellar damage does not cause adult-onset ASD
  • But somewhat consistent are deficits on sequencing tasks (van overwalle work) but mild to no deficits on ToM tasks (Beuriat, Cohen-Zimermann et al. 2022).
• Explanations for developmental differences between children and adult deficits:
  • Lesions in children could be larger and more likely to impinge on Crus I/II, thereby affecting social behavior to a larger degree
  • Lesions in children could affect deep nuclei and white matter tracts linking the cerebellum to the cerebrum to a larger degree.
  • Possible that the tasks used to assess social cognition in adults do not have sufficient variance and/or do not capture the nature of cerebellar social deficits.
  • Causes of cerebellar damage in early life are different than in adulthood.
• Explaining the age gradient:
  • Forward internal model explanation - cerebellum receives a command signal from the cerebrum, compares that command to sensory feedback, and then creates a prediction error signal that fine tunes the command based on what the desired outcome is and sends it back to the cerebrum (Ito 2008). This is in contrast to the inverse internal model in which the cerebellum receives a desired outcome from the cerebrum and produces the action that reaches that outcome.
  • Both are supervised learning models which rely on large amounts of data where the action to outcome pairings are known, the inverse model is optimal when extensive training has occurred.
  • Proposal is that the cerebellum builds and deploys mental models that shift from one dominant model type to another model-type over the course of development.
  • As a child, the cerebellum’s forward internal model mechanism helps create social mental models of the world that offer predictions of outcomes that are constantly being tested and retested to refine the model. Prediction errors allow the model to be adaptive when encountering new or uncertain social situations (Sokolov et al. 2017). These models would be stored in portions of the cerebral cortex referred to as the “social brain”. Frosch et al. (2022): if for some reason the cerebellum was not able to build social mental models or was not able to access them (because of damage to structural connections), then individuals would find it hard to predict how others might act or how their words or actions might be received (a la developmental diaschisis idea from wang et al. 2014: the idea being that the cerebellum drives the maturation of functional circuits in the evolutionarily newer and more functionally plastic association cortex of the cerebrum to which it is connected - cerebellar damage early in life causes downstream dysfunction in the cerebrum because the cerebellum cannot create forward models that functionally tune the frontal lobe.
• What is happening between childhood and adulthood?
  • By adulthood, the cerebellum has already built up a repetoire of highly predictive social mental models in social thoughts or behavior. Therefore, the forward model ceases to be important for social behavior, and there is a shift in the dominant model executed by cerebellar computations.
  • The dominant model now becomes the inverse internal model of the cerebellum, which executes automated thoughts and behaviors. Therefore, social deficits following cerebellar damage in adulthood would likely take the form of slowness or difficulty initiating an otherwise automated response.
  • Interpreting existing fMRI studies in adults through the lens of this model can be difficult. If the task requires new social rules or behaviors with error-driven feedback, the activations likely reflect the deployment of the forward model. Maybe it’s also possible that the cerebellum receives the input and concludes via low prediction errors, that no adjustments need to be made to what the cerebellum is computing.
• Ideas for cerebellum learning study
  • Cerebellar learning study: Crus I/II will be activated when learning the new body language and activations will decrease more quickly in individuals who learn more quickly. Social-activated regions of Crus I/II will be functionally synchronized ith socially sensitive regions of the cerebrum.
  • Adults with cerebellar damage should be able to learn alien social norms but they’ll do so extremely slowly and using explict, language-based learning mechanisms.