Abstracts

Rationale: Neuroanatomical, neuroimaging and clinical evidence have broadened our understanding of the cerebellum to include roles beyond sensorimotor function. Posterolateral cerebellum, primarily lobules VI and VII are activated during cognitive tasks. Right cerebellar activation is reported in functional imaging language paradigms in subjects with left cortical language dominance. We studied functional topography and laterality of activation in the cerebellum to investigate crossed cerebro-cerebellar circuits in healthy controls and patients with epilepsy.Methods: 110 patients (57 males; mean age 23.1 12.3 yrs, range 4.5-57 yrs) with left hemisphere focal epilepsy (mean onset age 12.1 8.3 yrs, range 0.1-38 yrs; mean duration 11.5 11.2 yrs, range 0-55 yrs) underwent 3T EPI BOLD fMRI with an auditory description decision task. 88 patients had temporal lobe and 22 had frontal lobe foci. We also studied 53 healthy controls with left hemisphere language dominance (26 males; mean age 26.9 7.6 yrs). Data were analyzed in SPM8. We calculated regional laterality indices [LI=(L-R)/(L+R)] for cerebellum (CBL), inferior frontal gyrus (IFG), middle frontal gyrus (MFG) and Wernicke s area (WA) using a bootstrap method, and defined 28 cerebellar lobules using Wake Forrest Pick Atlas. Patients had atypical language when either WA or IFG was right dominant (LI<-0.20) or both regions bilateral (LI<|0.20|).Results: Both controls and patients had activation in right cerebellum and traditional language networks in left fronto-temporal regions (FWE corrected p<0.05, >20 voxels per cluster). CBL LI correlated with LI in IFG, MFG & WA (p?0.001). CBL LI did not differ between patients (mean CBL LI= -0.38 0.54) and controls (mean CBL LI= -0.53 0.52) (p>0.05). However, mean CBL LI was more right lateralized in patients with left language dominance (n=92; mean CBL LI= -0.50 0.47) compared to patients with atypical language dominance (n=18; mean CBL LI=0.20 0.52) (p<0.001). CBL LI did not vary with age, age of onset, epilepsy duration, gender, handedness, or lobe of focus. Healthy controls had clusters of activation in right lobule VI (72 voxels, T=6.48), Crus I (531 vox, T=7.79), and Crus II (76 vox, T=8.46); and a small cluster in left lobule III-V (31 vox, T=6.82). Patients with typical language had clusters in right Crus I (263 vox, T=6.84) and lobule IX (106 vox, T=7.20), and more activation than controls in left lobule III-V (185 vox, T=8.90). Patients with atypical language had activation in left Crus II (85 vox, T=6.51), and none on the right.Conclusions: Although laterality in the cerebellum is comparable in healthy controls and patients with left focal epilepsy, functional topography of activation differs during a language task, suggesting functional malleability of cerebellar networks. Compared to controls, patients with left language dominance had increased activation in lobule IX and decreased activation in right VI and Crus II. Patients with atypical language showed a more left lateralized pattern of cerebellar activation, supporting the idea of crossed cerebro-cerebellar networks.