Cerebellar lobules and dentate nuclei mirror cortical force-related-BOLD responses: Beyond all (linear) expectations

Abstract

The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum-optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non-linear associations between cerebellar activations and forces. We showed extensive non-linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD-force relationship that is region-dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp 38:2566-2579, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: FMRI; SUIT; cerebellum; dentate-nuclei; force; non-linearity; power grip.

Figure 1

A flowchart summarizing the cerebellar analysis performed using SUIT as described in the steps 1–11 above. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Anatomical identification of cerebellar regions (A); effects of the 0th order form (B); effects of forcerelated forms (C). All effects are projected onto the SUIT flattened map. In the map, right is right (ipsilateral) and the threshold for (normalized) effect sizes were set at t‐value > 3, for display purposes only (significant results are discussed in the text at a corrected level of t‐value > 3.92. These are shown as white contours in the figure). Note, that the map was thresholded across all force related effects by the largest effect size. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Example of BOLD responses (Z axis) based on fitted polynomial functions of GF (Y axis) over poststimulus time (PST) (X axis). In other words, these graphs show the estimated changes in the haemodynamic (BOLD) response signal per unit change of the regressor coefficient. Importantly, this figure shows the relationships between GF and BOLD response based on all components of the polynomial expansion. This figure shows examples from voxels in different lobules (A. VI, B. V, C. VIII, D. VII) based on the group results (i.e., polynomial coefficients and canonical HRF). [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Activations projected onto the dentate nuclei showing examples of the main effect of gripping (i.e., 0th order) using a threshold of T‐value ≥ 2, for illustration purposes (significant results are indicated using white arrows in the figure). In these effect maps, right is right (ipsilateral) and all activations are projected on axial sections (white numbers indicate z‐coordinate). R: rostral; C: caudal; V: ventral; D: dorsal. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Activations projected onto the dentate nuclei showing examples of force related effects surviving a threshold of T‐value ≥ 2, for illustration purposes (significant results are indicated using white arrows in the figure). In the effect maps, right is right (ipsilateral) and all activations are projected on axial sections (white numbers indicate z‐coordinate). R: rostral; C: caudal; V: ventral; D: dorsal. [Color figure can be viewed at http://wileyonlinelibrary.com]