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Articles, Behavioral/Cognitive

Placebo-Induced Changes in Excitatory and Inhibitory Corticospinal Circuits during Motor Performance

Mirta Fiorio, Mehran Emadi Andani, Angela Marotta, Joseph Classen and Michele Tinazzi
Journal of Neuroscience 12 March 2014, 34 (11) 3993-4005; DOI: https://doi.org/10.1523/JNEUROSCI.3931-13.2014
Mirta Fiorio
1Department of Neurological and Movement Sciences, University of Verona, 37131 Verona, Italy,
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Mehran Emadi Andani
1Department of Neurological and Movement Sciences, University of Verona, 37131 Verona, Italy,
2Department of Biomedical Engineering, University of Isfahan, 81746-73441 Isfahan, Iran, and
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Angela Marotta
1Department of Neurological and Movement Sciences, University of Verona, 37131 Verona, Italy,
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Joseph Classen
3Department of Neurology, University of Leipzig, 04103 Leipzig, Germany
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Michele Tinazzi
1Department of Neurological and Movement Sciences, University of Verona, 37131 Verona, Italy,
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    Figure 1.

    A, Schematic representation of the experimental setup. The subject sat comfortably at a table in front of a PC monitor displaying a starting line (black line), a target zone (colored lines), and a cursor (green dot). The lowest line of the target zone (green) represented 80% of the subject's MVF, whereas the highest line (light blue) represented 140% of MVF, as measured for each participant in the calibration phase at the beginning of the experiment. The task was to press a piston with the right index finger as strongly as possible to reach the higher lines of the target zone. The pressures against the piston were recorded by a force transducer and converted in vertical displacements of the cursor by a DAQ board. Right, Magnified view of the hand constraint. A holder was used to keep the hand static during the performance of the motor task and to allow only movements with the index finger. B, Illustration of a trial of the motor task. When the cue START appeared on the PC monitor, the subjects could start the trial by pressing the mouse key with the left hand. The trial started with the appearance of the black line at the bottom of the monitor, the yellow cursor, and the lines of the target zone. As soon as the subject pressed the piston, the cursor moved toward the target zone; when entering the target zone, it changed from yellow to green. Subjects had to maintain the cursor in the highest position they could achieve until the end of the trial. Each trial lasted 1100 ms. C, Timeline of the experimental protocol with a representation of the sessions sequence (baseline, manipulation, and final) and TENS application. The dashed arrows indicate the moment at which the subjective scales were administered. As schematically shown in the picture, the controlTENS group and the two experimental groups (expverbal+conditioning and expverbal) received different verbal information about the effects of TENS. Moreover, in the manipulation session, the groups underwent different procedures: the expverbal+conditioning group performed the motor task with a surreptitious amplification of the cursor's excursion range (conditioning procedure), whereas the expverbal group and the controlTENS group performed the motor task without any amplification. Crucial for our interest was the comparison of performance before and after manipulation (i.e., in the baseline and final sessions). An additional control group performed the motor task in the same three sessions, but without TENS application (controlnoTENS). D, Illustration of a trial of the TMS task. When the cue START appeared on the PC monitor, the subjects could start the trial by pressing the mouse key with the left hand. The trial started with the appearance of the black line at the bottom of the monitor, the yellow cursor, the lines of the target zone, and a red line. The red line represented the 30% of MVF as measured in the calibration phase. Subjects had to maintain the cursor on the red line until the end of the trial; because the task was not to achieve the highest lines, the lines of the target zone were dimmed compared with the motor task. Each trial lasted 5000 ms. Right, Magnified schematic view of the TMS pulse delivery is presented. If the cursor remained stable on the red line, for at least 500 ms (i.e., when the subject exerted a stable pressure of 30% MVF), the TMS pulse was triggered. The pulse was delivered randomly in a time window ranging from 500 to 1300 ms from the onset of the 30% MVF stable pressure. The TMS task was performed after the motor task, in the baseline, manipulation and final sessions. During TENS application, the electrodes for EMG recording were removed from the FDI muscle to apply the TENS electrodes. Afterward, the EMG electrodes were positioned again over the FDI muscle.

  • Figure 2.
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    Figure 2.

    Illustration of the behavioral and subjective data. A, Force profile obtained from the average of the 50 trials of the baseline (dashed lines) and final (continuous lines) sessions in one subject of the expverbal+conditioning group (red lines), one subject of the expverbal group (magenta lines), one subject of the controlTENS group (green lines), and one subject of the controlnoTENS group (blue lines). B, Mean values (±SE) of Forcepeak normalized to MVF. The expverbal+conditioning group (red line) increased the level of force in the final session compared with the baseline, and a tendency was observed in the expverbal group, whereas the controlTENS and controlnoTENS groups (green and blue lines) showed an opposite pattern, with a reduction of force. C, Percentage (±SE) of strong pressures. The expverbal+conditioning group pressed the piston more often with strong pressures in the final session compared with the baseline, whereas the two control groups showed the opposite pattern. A significant difference between groups was found in the final session. D, Mean scores (±SE) given at the expectation scale. The question related to this scale was as follows: “Do you expect that your performance will change compared with the very first session? If yes, how?” Subjects could answer on a 7 point NRS, in which positive scores indicate that they expected a benefit in force production after TENS. The expverbal+conditioning group and the expverbal group expected a positive change of performance before starting the final session. E, Mean scores (±SE) related to the efficacy of the treatment. The question related to this scale was as follows: “Was the treatment really effective in changing your performance? If yes, how much?” Subjects could answer this question on a VAS scale. Scores are reported only for the groups in which TENS was applied. As shown in the figure, the two experimental groups reported that the treatment was more effective compared with the controlTENS group. F, Mean (±SE) subjective perception of force. Perception of force was higher in the final compared with the baseline session in the two experimental groups. G, Mean scores of the sense of effort (given on the Borg scale; Borg, 1970). The four groups did not change the perception of effort from baseline to final session. **p < 0.01. *p < 0.05. ∼p < 0.059.

  • Figure 3.
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    Figure 3.

    Illustration of the mean (±SE) neurophysiological data obtained from the four groups of participants at the TMS task in the baseline and final sessions. A, Mean MEP amplitude (in millivolts) recorded form the FDI muscle. The expverbal+conditioning (red line) and the expverbal (magenta lines) groups showed an increase in amplitude from the baseline to the final session, whereas the controlnoTENS group showed a decrease. B, Mean MEP amplitude recorded from the ADM muscle. No difference has been found between the groups and the sessions, suggesting that the effect is specific for the FDI. C, Mean duration of the CSP (in milliseconds). A significant shortening of the CSP can be observed in the expverbal+conditioning group from baseline to final session and in respect to the two control groups in the final session. **p < 0.001. *p < 0.05. ∼p < 0.059.

  • Figure 4.
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    Figure 4.

    Representative neurophysiological traces recorded from the FDI muscle in one subject of the expverbal+conditioning group (red traces), one subject of the expverbal+conditioning group (magenta traces), one subject of the controlTENS group (green traces), and one subject of the controlnoTENS group (blue traces). The traces represent the average of the 16 trials of the TMS task in the baseline session (top) and in the final session (bottom). TMS pulse was delivered at 0 ms. MEP amplitude is reported in millivolts and CSP duration is shown in milliseconds. As illustrated in the figure, MEP amplitude was higher in the subjects of the experimental groups at the final session compared with baseline, whereas it was lower in the two subjects of the control groups. CSP duration was shorter in the final than in the baseline session in the subject of the expverbal+conditioning group.

  • Figure 5.
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    Figure 5.

    A, Illustration of the mean (±SE) force level (N) of the four groups of participants in the TMS task. This task was performed after the main motor task in the baseline and final sessions. The TMS pulse was delivered when participants kept the cursor on the red line (30% MVF). Mean force level was computed from the onset of the trial until the delivery of the TMS pulse because TMS caused perturbation of the index finger pressure. As shown in the figure, the four groups exerted the same amount of force in this task, both in the baseline and final sessions. This suggests that the MEP amplitudes recorded during this task were not influenced by bottom-up factors, such as the amount of impressed force. B, Mean (±SE) EMG background activity (in microvolts) recorded from the FDI muscle before the TMS pulse. As shown in the figure, the four groups of participants had the same amount of EMG activation before MEP onset, both in the baseline and final sessions, suggesting that the MEP amplitude was not influence by the preceding EMG activity. C, Mean (±SE) EMG background activity (in microvolts) recorded from the ADM muscle before the TMS pulse. This muscle was not involved in the task; and, as shown in the figure, the amount of EMG activation was very low and comparable in the four groups of participants. D, Mean (±SE) MEP amplitude (millivolts) recorded at rest from the FDI muscle. As shown in the figure, the four groups of participants display the same amplitude both in the baseline (before starting the experiment) and final session (after completing the experiment). This suggests that the change in corticospinal excitability does not generalize at the rest condition. E, Mean (±SE) MEP amplitude (millivolts) recorded at rest from the ADM muscle. Results were the same as obtained from the FDI muscle.

  • Figure 6.
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    Figure 6.

    Input–output curves of the FDI (A) and ADM (B) muscles measured in the expverbal group before and after the experimental procedure. Mean (±SE) MEP amplitude of the two muscles are represented for different intensities of stimulation (in percentage of SI). As shown, MEP amplitudes progressively increase with higher stimulus intensities, but no change has been found between the baseline and final sessions. Right small panels, Mean (±SE) slope values are represented for the FDI and ADM muscles in the baseline and final sessions. Again, no difference was found across sessions.

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The Journal of Neuroscience: 34 (11)
Journal of Neuroscience
Vol. 34, Issue 11
12 Mar 2014
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Placebo-Induced Changes in Excitatory and Inhibitory Corticospinal Circuits during Motor Performance
Mirta Fiorio, Mehran Emadi Andani, Angela Marotta, Joseph Classen, Michele Tinazzi
Journal of Neuroscience 12 March 2014, 34 (11) 3993-4005; DOI: 10.1523/JNEUROSCI.3931-13.2014

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Placebo-Induced Changes in Excitatory and Inhibitory Corticospinal Circuits during Motor Performance
Mirta Fiorio, Mehran Emadi Andani, Angela Marotta, Joseph Classen, Michele Tinazzi
Journal of Neuroscience 12 March 2014, 34 (11) 3993-4005; DOI: 10.1523/JNEUROSCI.3931-13.2014
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Keywords

  • corticospinal excitability
  • expectation
  • motor system
  • placebo effect
  • TMS

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