Excitability of the Ipsilateral Motor and Premotor Cortices during Unilateral Finger Movements: A Combined fMRI and TMS Study
Corresponding author: Dr. Woo-Kyoung Yoo, Dep. of Physical Medicine and Rehabilitation, 896, Hallym University Sacred Heart Hospital, Pyeoung-chon dong, Dongan-gu, Anyang, Gyeonggi-do 430-070, Republic of Korea, Tel: +82-31-380-3860; Email: firstname.lastname@example.org, email@example.com
The previous functional imaging studies have demonstrated that ipsilateral motor cortex activation occurred during complex motor tasks [1,2] and upon non-dominant hand movement in healthy volunteers [3,4]. While the functional role of ipsilateral activation is still a matter of debate, [2,3] Verstynen et al . described that the ipsilateral activation is not necessarily related to the execution of complex movements but is rather related to higher level of controls associated with action retrieval, preparation, and/or selection of the ipsilateral motor cortex. This view is in line with the results that were shown in patients with lesions of the central motor systems . A controversial issue that needs to be addressed here is the location of the ipsilateral activity. Many studies demonstrated ipsilateral motor cortex activation shifted to lateral and ventral area compared to contralateral activation during voluntary finger movements, and suggested the possibility of activation of the ipsilateral dorsal premotor cortex (PMd) rather than ipsilateral primary motor cortex (M1) in functional magnetic resonance imaging (fMRI) [7,8].
On the other hand, cortical excitability that was measured by transcranial magnetic stimulation (TMS) in the ipsilateral hemisphere while performing unilateral finger movements has been discussed mostly based on assumption of changing the excitability in the M1 as TMS stimulate the primary motor cortex [9-12]. It also reported strong facilitation likewise in imaging studies, while performing complex finger movements . Beyond the presumed changes in ipsilateral M1, interhemispheric interaction between bilateral M1 has been generally accepted to be induced by inhibition of contralateral M1 through transcallosal inhibition via corpus callosum .
SubjectsSeven healthy right-handed volunteers (five males and two females) between the ages of 19 and 24 (mean age: 21 years) participated in this study. The subjects’ handedness was assessed using the Edinburgh Handedness Inventory  and all subjects were deemed right-handed. We received the approval of the local ethics committee for the experimental procedures, and a written informed consent was obtained from all subjects.
The subjects were comfortably seated in a reclining armchair with both hands pronated on a pillow, and they were instructed to keep their hand and forearm muscles as relaxed as possible. During stimulation, surface electromyography (EMG) was recorded and monitored continuously on-line (Neuroscreen Plus, Erich Jaeger, Germany) using Ag-AgCl electrodes. Active electrodes were attached to the skin overlying the abductor pollicis brevis (APB) muscle. Reference electrodes were placed over the metacarpophalangeal joint. The EMG signals were filtered (10-2000 Hz), amplified, displayed and stored for offline analysis.
Transcranial magnetic stimulation. A MagStim 200® magnetic stimulator (MagStim Company, UK) with a maximum output intensity of 2.0 T was used for the TMS of the motor cortex, along with a 70-mm figure-of-eight coil. Specifically, the figure of eight coil was positioned tangentially to the scalp at an angle of 45° from the mid-sagittal line such that the electromagnetic current flow perpendicular to the central sulcus. The coil was systematically moved in 1 cm steps at constant supra-threshold stimulus intensity to detect the optimal scalp location (“the hot spot”) for eliciting stable MEPs in the APB muscle. Once the hot spot had been identified then marked with a pen to ensure the constant positioning of the coil throughout the experiment. The resting motor threshold (RMT) was determined as the minimum TMS intensity that produced at least five MEPs of ≥50 μV peak-to-peak amplitude out of 10 consecutive trials delivered at a rate of 4-5 s interstimulus interval . The test stimulus intensity was determined to be 130% of the resting motor threshold. The subjects were asked to remain silent each time stimulation was delivered to avoid speech-induced modulation of cortical excitability. The subjects were also monitored for drowsiness and asked to keep their eyes open throughout the experiment.
Prior to the experimental procedure, all subjects were trained task by using a metronome set at 1 Hz. Three different conditioning tasks were used for the experiment. The subjects kept their hands at rest for the control task (task 1). For the task 2, they performed 1-Hz opposition movements of the 3rd finger to the thumb (the simple movement). The task 3 was composed of alternating thumb opposition movements to the other fingers repeatedly in the following order: 5th, 3rd, 4th and 2nd finger, (the complex movement). The tasks were performed on both hands, and the sequence of which hand was used and
the task was randomized and counterbalanced (Figure 1).
Figure 1. Experimental design for transcranial magnetic stimulation (TMS). Single pulse TMS were applied over the primary motor cortex (M1) that was ipsilateral to the moving hand and the motor evoked potentials (MEPs) were obtained from the Abductor Pollicis Brevis muscle of the opposite hand.
A 1.5 T Intera 9.0 Philips MRI system was used for this study. A T1 weighted anatomical scan was acquired from each subject [MPRAGE 3D, TR (repetition time) = 25 ms, TE (echo time) = 4.6 ms, Flip angle = 30o, FOV (field of view) = 230.0 and matrix = 256 x 256]. For the functional scan, the task were presented on the screen using SuperlabPro 2.0 software (Cedrus Co., Phoenix, AZ) and a 5 min echo-planar imaging that consists of alternating 15 sec blocks of rest and movement was performed (20 x 5 mm axial slices, TE = 30 MS, TR = 3000 ms, FOV = 230 and matrix = 128 x 128). The simple or complex movements for the right or the left hand were randomly arranged in the separate blocks.
As a first step, the MEP amplitude data for each of the tasks were transformed to a log scale after testing for normality (Kolmogorov–Smirnov tests). To test the statistical significance of the MEP amplitude changes according to the movement complexity and the dominance of the hand, we conducted multivariate analysis (a mixed model), the movement complexity (rest, simple and complex) and the dominance of the hand (dominant and non-dominant) as factors. As a second step, in order to test the relationship between the changes of the MEP amplitude and the relative hemodynamic changes that were noted for each brain area, i.e., the ipsilateral PMd and the ipsilateral M1, we also conducted multivariate analysis applying a mixed model for continuous dependent variables (ie, the changes of the MEP amplitude and the relative hemodynamic changes) by using the complexity of the movements and the dominance of the hand as independent variables. We analyzed this relationship by setting the relative hemodynamic changes of the ipsilateral PMd and the ipsilateral M1 as the independent variables, and the relationship could be expressed as a linear equation.
For all the subjects, the mean baseline cortical excitability threshold was 65 ± 10 (mean ± SD%). The mean baseline MEP amplitude was 1.37 ± 0.55 mV. The average MEP amplitude for the simple movements of the dominant hand was 0.78 ± 0.21 mV, and that of the non-dominant hand was 1.07 ± 0.33 mV. In addition, for the complex finger movements, the MEP amplitude for the dominant hand movement was 1.56 ± 0.79 mV, and that of the non-dominant hand was 1.96 ± 0.95 mV. The MEP amplitude obtained from the ipsilateral hand movements showed bigger changes for the movements of the non-dominant hand than that of the dominant hand (F(1,6) = 45.41, p = 0.0005), and also for the complex movements than that of the simple movements (F(2,12) = 89.21, p < 0.0001) (Figure 2).
Figure 2. The figure shows the differences in the amplitudes of motor evoked potentials (MEPs) that were obtained by magnetic stimulation of the ipsilateral primary motor cortex (M1) during resting, and simple and complex finger movements of the unilateral hand. Error bars indicate the standard deviation. *P<0.01, ** P<0.001.
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A2012562).
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