Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum

Abstract

Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data.

Major findings: (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

Keywords: Force; MVC; Power grip; Visuomotor task; fMRI.

Fig. 1

A diagram describing the steps that each subject followed. a The rubber flexible compatible MRI sqeezeball; b instructions for measuring each subject’s MVC prior to scanning; c–g the anonymous GF levels starting from 20 % with a step of 10–60 % of MVC. h–j Examples of a cued trial where h is the cue starting with an instructed sentence “Squeeze AND HOLD”, i is an example indicating that the response has not reached the required GF level while j shows that the response exceeds the required GF level and a red bar warns subjects. Lastly, k shows a cross sign indicating a rest time

Fig. 2

Grip performances. a Means of MVC ± standard deviation. (SD). Averaged MVC (±SD) was: for all trials: 39 (13), 20 %: 22 (2), 30 %: 30 (2), 40 %: 40 (2), 50 %: 47 (2), 60 %: 58 (2). b Means of grip duration (s) ±SD. Averaged duration (±SD) was: for all trials: 2.83 (0.32), 20 %: 2.65 (0.59), 30 %: 2.85 (0.11), 40 %: 2.78 (0.26), 50 %: 2.9 (0.09), 60 %: 2.99 (0.08)

Fig. 3

Example of BOLD responses (Z axis) of the fitted polynomial orders of GF responses (Y axis) at the defined post-stimulus time (PST) (X axis) at the subject level (fixed effect analysis). The figure shows different ROIs (a left BA 4a; b left BA 7; c right BA 6; d right BA 6) created based on the group results

Fig. 4

Brain activations (T values) at the group level corresponding to fitting polynomials of different orders to the BOLD signal response. The estimated shape of the fitted orthogonalized polynomial function is shown for each order next to the corresponding image displaying significant clusters. In the images, clusters are corrected at p < 0.05 after using an initial height threshold of 0.001 (for display purposes); right is right and left is left. A T value colour bar is shown below the images

Fig. 5

a Clusters of force-related effects were thresholded (using a voxel height of 0.001 and corrected (FWE) clusters) and the maximum t values at each voxel among all the force related orders are shown (hot colours are positive order responses and cold colours are negative responses). This is done at the group level for the purpose of illustration. In the map, right is right. b The 0th order activations, shown in light blue, and all force related orders, shown in yellow, are overlaid; overlapping areas are shown in dark red. The dark red areas represent the areas that are activated as a main effect of movement as well as modulated by GF levels. Note that it is not necessarily to observe a force related area that is also seen at the 0th order (e.g. yellow areas). In the map, right is right

Fig. 6

The TSNR map for the whole brain with the force-related activation areas outlined on top of the map (red traces). The average TSNR values for the whole brain and within the responded activations per order are shown in the bar graph. In the map, right is right