Weight-specific anticipatory coding of grip force in human dorsal premotor cortex

Abstract

The dorsal premotor cortex (PMd) uses prior sensory information for motor preparation. Here, we used a conditioning-and-map approach in 11 healthy male humans (mean age 27 years) to further clarify the role of PMd in anticipatory motor control. We transiently disrupted neuronal processing in PMd, using either continuous theta burst stimulation (cTBS) at 80% (inhibitory cTBS) or 30% (sham cTBS) of active motor threshold. The conditioning effects of cTBS on preparatory brain activity were assessed with functional MRI, while participants lifted a light or heavy weight in response to a go-cue (S2). An additional pre-cue (S1) correctly predicted the weight in 75% of the trials. Participants were asked to use this prior information to prepare for the lift. In the sham condition, grip force showed a consistent undershoot, if the S1 incorrectly prompted the preparation of a light lift. Likewise, an S1 that falsely announced a heavy weight produced a consistent overshoot in grip force. In trials with incorrect S1, preparatory activity in left PMd during the S1-S2 delay period predicted grip force undershoot but not overshoot. Real cTBS selectively abolished this undershoot in grip force. Furthermore, preparatory S1-S2 activity in left PMd no longer predicted the individual undershoot after real cTBS. Our results provide converging evidence for a causal involvement of PMd in anticipatory downscaling but not upscaling of grip force, suggesting an inhibitory role of PMd in anticipatory grip force control during object lifting.

Figure 1.

Experimental design. A, Time line of the experimental procedures. See Materials and Methods for further details. TMS/MEP = Measurements of MEP with single-pulse TMS of left primary motor hand area. B, Visually guided grip-and-lift force task. During fMRI, subjects were presented with a S1 pre-cue (red color) and a S2 go-cue (green color) with a variable delay between S1 and S2. The cues were projected on the screen for 1 s, thereafter an orange or gray cross was projected during a jittered period of 2–8 s. The shape of the stimulus indicated the weight to be lifted. A circle or a square predicted a light (100 g) or a heavy (250 g) weight. In 75% of the trials, the preparatory S1-cue correctly predicted the S2 cue. Depending on the combination of S1 and S2 cues, there were two trial types with correct pre-cue (HH, LL) and two trial types with incorrect pre-cue (LH, HL).

Figure 2.

Conditioning effects of cTBS to left PMd on corticospinal excitability in left M1_HAND. Group data of relative changes in mean peak-to-peak amplitude of the MEPs normalized to the mean amplitude before the intervention. The filled squares give the MEP amplitudes after real cTBS_80% of left PMd. The open diamonds represent the MEP amplitudes after sham cTBS_30% of left PMd. The first post-cTBS measurement was performed 5 min after the end of cTBS before fMRI. The second post-cTBS measurement was performed after the end of the fMRI session (i.e., ∼55 min after the end of cTBS).

Figure 3.

Impact of the validity of the pre-cue on the grip force curves. Mean GF, GF rate, LF, and LF rate for the four different trial types of a representative subject are shown. Normal lines indicate the correctly pre-cued trials; the dotted lines represent the mean data of the incorrectly pre-cued trials. A depicts the mean data of trials requiring subjects to lift a heavy weight, while B shows the mean data of trials requiring a light lift. Trial types according to S1–S2 sequence: HH, LL, LH, HL.

Figure 4.

Effect of the validity of the pre-cue on grip and lift force. The white columns give the mean overshoot in force production caused by an incorrect S1 pre-cue indicating a heavy weight. The overshoot corresponds to the ratio between HL and HH trials. The black columns give the mean undershoot in force production caused by an incorrect S1 pre-cue indicating a light weight. The undershoot corresponds to the ratio between LH and LL trials. Trial types according to S1–S2 sequence: HH, LL, LH, HL. Error bars indicate SD. Paired t test, *p < 0.001.

Figure 5.

Effect of real cTBS_80% of left PMd on maximal grip force. The white columns give the mean overshoot in force production (i.e., the ratio between HL and HH trials) caused by an incorrect S1 pre-cue indicating a heavy weight. The black columns give the mean undershoot in force production (i.e., the ratio between LH and LL trials) caused by an incorrect S1 pre-cue indicating a light weight. Compared with sham cTBS_30%, real cTBS_80% abolished the undershoot in maximal grip force caused by an incorrect lightweight cue. The asterisk denotes a significant difference of the pairwise comparison at p < 0.05. Error bars indicate SD.

Figure 6.

Regional increases in BOLD signal during preparation (S1–S2 interval). A, Main effect of preparation regardless of the weight indicated by the S1 pre-cue. The sagittal, coronal, and axial slices show the regions that showed an increase in BOLD signal during the preparation of a lift (heavy and light). B, Relative increases in BOLD signal during the preparation for lifting a heavy weight relative to preparing for lifting a light weight. The statistical parametric maps are based on the fMRI data recorded after sham cTBS_30% of left PMd.

Figure 7.

Linear relationship between regional activation during motor preparation and the relative undershoot in maximal grip force in trails where an incorrect S1 pre-cue announced a light weight after sham cTBS_30% (A) or real cTBS_80% (B) of left PMd. A, In the control session without effective cTBS, preparatory activity during the S1–S2 period predicted the individual undershoot in maximal grip force. The higher the preparatory activity in the left PMd, the larger was the undershoot in trials with an incorrect S1 pre-cue indicating a light weight. B, This linear relationship was abolished after real cTBS_80% of left PMd. The left panels show axial slices of the statistical parametric map for the linear relationship between preparatory activity and force undershoot. The corresponding scatter plots for the peak voxel in left PMd are presented on the right (x, y, z = −30, −3, 54). The parameter estimates of preparatory BOLD signal changes are plotted along the y-axis. The maximal grip force ratios (LH/LL trials) are displayed along the x-axis. The gray color marks the area with negative LH/HH force ratio (i.e., undershoot). The regression line gives the estimated linear relation.

Figure 8.

Relationship between cTBS-induced change in force undershoot and weight-specific preparatory activity in left rostral SMA. Subjects in whom fMRI revealed a relative increase in preparatory S1–S2 activity for light lifts (relative to heavy lifts) after real cTBS_80%, showed no or little change in grip force undershoot (LH/HH ratio) after real cTBS_80%. Conversely, real cTBS_80% induced a clear reduction in grip force undershoot in those subjects who showed an increase in preparatory S1–S2 activity for light lifts (relative to heavy lifts) after real cTBS_80%. The axial slice (top) illustrates the cluster in left rostral SMA showing a linear relation between cTBS-induced change in force undershoot and weight-specific preparatory activity. The corresponding scatter plot for the peak voxel in left rostral SMA is illustrated in the bottom (x, y, z = −6, 18, 54). The regression line gives the estimated linear relation.