Stuart McAfee Lab

Surgical removal of tumors in the cerebellum can inadvertently cause damage with neurological impact, not only from the physical removal of the tumor and damage to the surrounding margins, but also indirectly through disrupted synaptic connections. Downstream neurological effects can occur as the brain evolves to function after undergoing a surgically induced structural change. 

Alongside colleagues in the Sitaram lab, we have taken a neuroscience approach to studying PFS and localized surgical injuries to specific regions in the brain. Comparative analysis of magnetic resonance images (MRI) of the cerebellum and brainstem of children with PFS versus a non-PFS medulloblastoma control group allowed us to identify regions of the brain and brain circuits related to the symptoms of PFS, which can be heterogeneous in nature. We also conducted connectivity analyses to measure how consistently co-active specific areas of the brain were, which identified PFS-related alterations in brain function. 

My work has also shifted the field’s understanding of mutism in PFS as I provided support for PFS-related impact on two branches of the speech motor system: one for planning language and articulating sound and another for creating vocal sounds. Analysis of functional MRIs showed a desynchronization between these two branches in patients with PFS-related mutism, highlighting a potentially unique and undiscovered role of the cerebellum in this syndrome.

We have also found evidence that periaqueductal grey (PAG) dysfunction plays a role in transient post-operative speech disruption in patients with PFS. Analysis of imaging data gathered before and after speech recovery allowed us to pinpoint the functional consequences of PAG dysfunction and, furthermore, to see the restoration of functional connectivity of the PAG once patients regained the ability to speak. These results helped us to understand the role of PAG in speech impairment and potentially identify novel pathways involved in speech recovery. 

As we look for ways to improve quality of life for pediatric cancer survivors, understanding PFS and how to ameliorate the risk is of the utmost importance. Due to the rarity of pediatric tumors in the posterior fossa, many care teams who come across these tumors are not well versed in the existence or treatment of PFS. I work with the Posterior Fossa Society to educate healthcare providers about the existence and impact of PFS on patients. 

I am also developing a risk-assessment tool that would use data from preoperative MRIs to generate a risk score for PFS. Preemptively identifying those at high-risk of developing PFS will provide valuable information to surgeons as they would be able to tailor their surgical treatment strategy to decrease the risk for PFS.