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bioRxiv · 10.1101/2024.10.31.621398

Bias-accounting meta-analyses overcome cerebellar neglect to refine the cerebellar behavioral topography

Magielse, N.·Manoli, A.·Eickhoff, S. B.·Fox, P. T.·Saberi, A.·Valk, S. L.
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Abstract

The cerebellum plays important roles in motor, cognitive, and emotional behaviors. Previous cerebellar coordinate-based meta-analyses (CBMAs) have complemented precision-mapping and parcellation approaches by finding generalizable cerebellar activations across the largest possible set of behaviors. However, cerebellar CBMAs face challenges due to inherent methodological limitations exacerbated by historical cerebellar neglect in neuroimaging. Here, we show overrepresentation of superior activations, rendering the null hypothesis of standard activation likelihood estimation (ALE) unsuitable. Our new method, cerebellum-specific ALE (C-SALE), finds behavioral convergence beyond baseline activation rates. It does this by testing experimental activations versus null models sampled from a data-driven probability distribution of finding activations at any cerebellar location. Task-specific mappings in the BrainMap meta-analytic database illustrated improved specificity of the new method. Multiple (sub)domains reached convergence in specific cerebellar subregions, supporting dual motor representations and placing cognition in posterior-lateral regions. We show our method and findings were replicable within NeuroSynth. Across both databases, 54/138 task domains or behavioral terms, including sustained attention, somesthesis, inference, anticipation and rhythm, reached convergence in specific cerebellar subgregions. Maps largely corresponded with cerebellar atlases but also showed many complementary mappings. Repeated subsampling showed that motor behaviors, and to a lesser extent language and working memory, mapped to especially consistent cerebellar subregions. Lastly, we found that cerebellar clusters were parts of brain-wide coactivation networks with cortical and subcortical regions implied in these behaviors. Together, our method further complements and expands understanding of cerebellar involvement in human behavior, highlighting regions for future investigation in both basic and clinical applications. Highlights[bullet] Biases in reported cerebellar activations strongly favors superior regions. [bullet]A new method of meta-analysis increases cerebellar mapping specificity and accuracy. [bullet]Large-scale meta-analyses support cerebellar roles in cognitive, affective, and motor behaviors. [bullet]54 task domains/ terms converged, including sustained attention, somesthesis, inference, anticipation and rhythm. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/621398v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@716ea0org.highwire.dtl.DTLVardef@11601fforg.highwire.dtl.DTLVardef@1dd1208org.highwire.dtl.DTLVardef@caf535_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

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Magielse, N., Manoli, A., Eickhoff, S. B., Fox, P. T., Saberi, A., Valk, S. L.. 2024-11-01. Bias-accounting meta-analyses overcome cerebellar neglect to refine the cerebellar behavioral topography. https://doi.org/10.1101/2024.10.31.621398

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