Functional imaging reveals movement preparatory activity in the vegetative state

Abstract

The vegetative state (VS) is characterized by the absence of awareness of self or the environment and preserved autonomic functions. The diagnosis relies critically on the lack of consistent signs of purposeful behavior in response to external stimulation. Yet, given that patients with disorders of consciousness often exhibit fragmented movement patterns, voluntary actions may go unnoticed. Here we designed a simple motor paradigm that could potentially detect signs of purposeful behavior in VS patients with mild to severe brain damage by examining the neural correlates of motor preparation in response to verbal commands. Twenty-four patients who met the diagnostic criteria for VS were recruited for this study. Eleven of these patients showing preserved auditory evoked potentials underwent functional magnetic resonance imaging (fMRI) to test for basic speech processing. Five of these patients, who showed word related activity, were included in a second fMRI study aimed at detecting functional changes in premotor cortex elicited by specific verbal instructions to move either their left or their right hand. Despite the lack of overt muscle activity, two patients out of five activated the dorsal premotor cortex contralateral to the instructed hand, consistent with movement preparation. Our results may reflect residual voluntary processing in these two patients. We believe that the identification of positive results with fMRI using this simple task, may complement the clinical assessment by helping attain a more precise diagnosis in patients with disorders of consciousness.

Keywords: consciousness; functional imaging; intention; movement preparation; vegetative state.

Figure 1

Flow chart of patient selection in each step of the study.

Figure 2

Regions of interest for premotor cortex drawn based on Picard and Strick's (2001) functional distinction. Shown are the ROIs drawn on the MNI-152 T1 template for right (dark blue) and left (light blue) PMd, right (yellow) and left (blue) pre-PMd, SMA proper (red) and pre-SMA (dark-red).

Figure 3

Functional results from the whole-brain fixed-effect univariate analysis. Activation of temporal (red squares) and premotor cortex (green circles) is shown for patients VS1 through VS5 (top to bottom) when comparing right-hand commands vs. rest. All BOLD activity maps are superimposed on each individual's structural image. Statistical threshold level was set at p < 0.003 for illustrative purposes.

Figure 4

Functional results from whole-brain fixed-effect univariate analysis. Activation for patients VS1 and VS2 when comparing right vs. left-hand commands. All BOLD activity maps are superimposed on each individual's structural image. Statistical threshold level is set at p < 0.003 for illustrative purposes.

Figure 5

Time course of ROI activity for left premotor cortex for VS1 and VS2. The gray horizontal bar shows when the commands were delivered. The solid black line corresponds to the “right hand vs. left hand” contrast, whereas the dashed line corresponds to the “left hand vs. right hand “contrast. Standard errors are shown for each contrast.” The gray line corresponds to the model's HRF.

Figure A1

Command induced activity in premotor cortex in healthy volunteers. Activity (in brown) corresponds to the results for the right vs. left-hand command contrast for each of the three control subjects (single subject fixed effects). t Maps are superimposed on the ROI map depicted in Figure 1 and overlaid on axial slices of the 152-MNI T1 template. See Table A1 for details on the contribution of each subject to this spatial pattern.

Figure A2

Results of the right vs. left movement contrast (red) superimposed on the original SPM masks for VS1 (A) and VS2 (B).

Figure A3

Results of the right vs. rest movement contrast (red) superimposed on the original SPM masks for VS3 (A), VS4 (B), and VS5 (C).