Cerebellar mutism is linked to midbrain volatility and desynchronization from speech cortices

Area of Science:

• Neuroscience
• Neuroimaging
• Speech Pathology

Background:

• Cerebellar mutism syndrome (CMS) is a complex disorder affecting speech, movement, and affect post-posterior fossa tumor removal.
• The pathogenesis of CMS is not fully understood, though projections from the fastigial nuclei to the periaqueductal gray area are implicated.
• Functional consequences of damage to these cerebellar projections remain poorly understood, particularly concerning the motor system for speech.

Purpose of the Study:

• To investigate functional changes in speech motor system brain areas using functional MRI (fMRI) in patients with medulloblastoma.
• To identify functional deficits associated with the acute phase of cerebellar mutism syndrome.
• To analyze the temporal evolution of functional connectivity during recovery from CMS.

Main Methods:

• Analysis of fMRI data from 124 participants with medulloblastoma (45 with CMS, 11 with other severe deficits, 68 asymptomatic).
• Data-driven parcellation to define functional nodes within speech motor control regions.
• Estimation of functional connectivity between nodes in acute and recovery phases; measurement of signal dispersion in the periaqueductal gray and red nuclei.

Main Results:

• Evidence of periaqueductal gray (PAG) dysfunction in acute CMS, characterized by abnormal volatility and desynchronization with neocortical language nodes.
• PAG functional connectivity normalized post-speech recovery, showing increased connectivity with the left dorsolateral prefrontal cortex.
• Amygdalae showed broad hyperconnectivity with neocortical nodes in the acute phase; stable, widespread cerebral connectivity differences were observed between groups.

Conclusions:

• Systemic changes in the speech motor system, centered on limbic areas controlling phonation, are evident in patients with CMS.
• PAG dysfunction following cerebellar injury contributes to the transient non-verbal episodes in CMS.
• Intact cerebellocortical projections may play a role in the chronic features of the disorder.