Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity

Abstract

The cerebellum processes information from functionally diverse regions of the cerebral cortex. Cerebellar input and output nuclei have connections with prefrontal, parietal, and sensory cortex as well as motor and premotor cortex. However, the topography of the connections between the cerebellar and cerebral cortices remains largely unmapped, as it is relatively unamenable to anatomical methods. We used resting-state functional magnetic resonance imaging to define subregions within the cerebellar cortex based on their functional connectivity with the cerebral cortex. We mapped resting-state functional connectivity voxel-wise across the cerebellar cortex, for cerebral-cortical masks covering prefrontal, motor, somatosensory, posterior parietal, visual, and auditory cortices. We found that the cerebellum can be divided into at least 2 zones: 1) a primary sensorimotor zone (Lobules V, VI, and VIII), which contains overlapping functional connectivity maps for domain-specific motor, somatosensory, visual, and auditory cortices; and 2) a supramodal zone (Lobules VIIa, Crus I, and II), which contains overlapping functional connectivity maps for prefrontal and posterior-parietal cortex. The cortical connectivity of the supramodal zone was driven by regions of frontal and parietal cortex which are not directly involved in sensory or motor processing, including dorsolateral prefrontal cortex and the frontal pole, and the inferior parietal lobule.

Figure 1.

Correlation maps for motor and prefrontal cortex. Top panel: the cortical masks in standard (MNI) space. (Left 2 columns a–h) Correlation maps for the bilateral cortical masks in standard space, showing the voxel-wise significance (Z-score) of the correlation with prefrontal and motor regions in the cerebral cortex. Maps are thresholded at Z > 1.6 (equivalent of P < 0.05 uncorrected) and presented with the left cerebellar hemisphere to the left of the image. Note the clear division of the cerebellar cortex into prefrontal and motor zones. Right 2 columns show the lobular structure of the cerebellum, after Schmahmann (2000), for the slices shown to the left. Note the correspondence between Lobules IV–VI and VIII (red and green) with the motor zone, and Lobule VII (blue) with the prefrontal cortex. Abbreviations: crI, Lobule VIIa Crus I; crII, Lobule VIIa crus II; V, VI, VIII, Lobules V, VI, and VIII.

Figure 2.

Lateralization of correlation maps for motor and prefrontal targets. Correlation maps for unilateral cortical masks in standard (MNI) space showing the voxel-wise significance (Z-score) of the correlation with prefrontal (blue) and motor/premotor (red) masks. Maps are thresholded at Z > 1.6 (equivalent of P < 0.05 uncorrected) and presented with the left hemisphere to the left of the image. Top row: Maps corresponding to the masks in the right cerebral hemisphere. Bottom row: Maps corresponding to the masks in the left cerebral hemisphere. The corresponding cortical masks are shown to the right of the figure. Note the relative strength of functional connectivity in the cerebellar hemisphere contralateral to the cortical mask. Maps represent only lateralized correlations, as correlations shared between cortical masks were partialled out (see Methods). Z-score scales are as in Figure 1.

Figure 3.

Correlation maps for 6 cortical regions. Presented in panels (a–f) are group correlation maps in standard (MNI) space, showing the voxel-wise significance (Z-score) of the correlation with each of 6 cortical masks in the cerebral cortex—from top to bottom, (a) visual area MT, (b) superior temporal cortex, (c) somatosensory cortex, (d) motor and premotor cortex, (e) posterior-parietal cortex, and (f) prefrontal cortex. Maps are thresholded at Z > 1.6 (equivalent of P < 0.05 uncorrected) and presented with the left cerebellar hemisphere to the left of the image. Each row corresponds to one cortical mask; the mask is shown to the right of the row. The set of cortical masks are shown together in the top panel. Note that the correlation maps fall into 2 patterns, shown in blue and red colorways above: the correlation maps for visual, auditory, somatosensory, and motor cortices were highly similar, and different from the correlation maps for prefrontal and posterior-parietal cortex, which in turn were similar to each other.

Figure 4.

Prefrontal and posterior-parietal subregions contributing to resting state connectivity with the posterior cerebellum. These connectivity maps were generated by taking the first Eigen time series from the cerebellar supramodal zone, and identifying voxels in the prefrontal and posterior-parietal cortex which correlated with it. Hence, they indicate which voxels within the cerebral–cortical regions contribute to the resting state correlation with the posterior cerebellum. Green tinted regions show the extent of the cortical regions. Blue statistic maps indicate group Z-scores thresholded at Z > 1.6 (equivalent of P < 0.05 uncorrected). Note that even at this low threshold, the parietal correlation map is limited to the inferior parietal lobule and medial parietal cortex—there is a clear boundary between significant and nonsignificant correlation at the intraparietal sulcus (especially clear on axial view). The prefrontal correlation map does not extend into the inferior frontal gyrus; a boundary at the inferior frontal sulcus is clearly visible in the coronal views. MFS, medial frontal sulcus; IPS, intraparietal sulcus.