Motor cortex activation during motor imagery of the upper limbs in stroke patients

Li Wang; Jingna Zhang; Ye Zhang; Linqiong Sang; Rubing Yan; Chen Liu; Mingguo Qiu

doi:10.4103/2226-8561.189523

ORIGINAL ARTICLE

Year : 2016 | Volume : 2 | Issue : 2 | Page : 72-79

Motor cortex activation during motor imagery of the upper limbs in stroke patients

Li Wang¹, Jingna Zhang¹, Ye Zhang¹, Linqiong Sang¹, Rubing Yan², Chen Liu³, Mingguo Qiu¹
¹ Department of Medical Image, College of Biomedical Engineering, Third Military Medical University, Chongqing, China
² Department of Rehabilitation, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
³ Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Date of Web Publication

30-Aug-2016

Correspondence Address:
Mingguo Qiu
Department of Medical Image, College of Biomedical Engineering, Third Military Medical University, Chongqing 400038
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2226-8561.189523

Abstract

Objective: The objective of this study was to analyze the functional brain activation in acute stroke patients during motor execution (ME) and motor imagery (MI) and to discuss the association between damaged brain structure and impaired brain function in stroke patients. Methods: The functional magnetic resonance imaging technique was used to observe activation of the brain during ME/MI of the upper limbs in 12 acute stroke patients (with the left brain damage) and 12 healthy controls. Results: During ME, the stroke patients appeared to be activated more strongly than the healthy controls in the ipsilateral primary motor areas. The MI of the affected hand in the stroke patients was not significantly different from that of the healthy hand. The nonmotor areas, the angular gyrus, and the fusiform gyrus were also activated during ME/MI. Conclusion: Structural damage in the brain is associated with the activation of brain function in acute stroke patients. Ipsilateral inhibition is reduced in stroke patients during ME and the damaged brain needs to recruit more brain areas to complete the desired action due to motion difficulties resulting from brain damage. The participation of nonmotor brain areas in ME/MI indicates that cortical reorganization may contribute to the restoration of motor function following stroke. MI can be used to improve injured brain areas, helping with the rehabilitation of stroke patients.

Keywords: Functional magnetic resonance imaging, motor execution, motor imagery, stroke

How to cite this article:
Wang L, Zhang J, Zhang Y, Sang L, Yan R, Liu C, Qiu M. Motor cortex activation during motor imagery of the upper limbs in stroke patients. Digit Med 2016;2:72-9

How to cite this URL:
Wang L, Zhang J, Zhang Y, Sang L, Yan R, Liu C, Qiu M. Motor cortex activation during motor imagery of the upper limbs in stroke patients. Digit Med [serial online] 2016 [cited 2023 Jun 8];2:72-9. Available from: http://www.digitmedicine.com/text.asp?2016/2/2/72/189523

Introduction

Motor deficits are one of the main and often most debilitating deficits after brain damage. Stroke is a major cause of morbidity and invalidity in the modern society. ^[1] Patients who survive a stroke usually recover some of the functionalities that is compromised by the stroke within 3 months. Physical therapy is often used to treat these stroke-related motor deficits. The theory of cortical plasticity postulates that ^[2] continuous training can recover the lost motor function when part of the brain cortex is damaged and motor dysfunction occurs. In recent years, motion imaging technology has been considered an important new procedure in the rehabilitation of this disorder. ^[3]

Motor imagery (MI) can be defined as the internal reactivation of a first-person motor program which is governed by the principles of central motor control without any overt motor output. ^[4],[5] MI activates the sensorimotor system without obvious movement and has the same neural mechanisms with motor execution (ME). ^{[6],[7],[8],[9],[10]} An increasing number of clinical studies have shown that MI rehabilitation is suitable for stroke patients, especially for those who have a great difficulty in moving their bodies. ^{[5],[11],[12],[13]}

Despite many studies have investigated the use of MI in rehabilitation, the neural mechanisms of exercise in the treatment of stroke patients are not very clear. These mechanisms could have important implications for treating stroke patients who have been treated with MI. We have previously explored the relationship between activated brain areas and age during simple finger ME/MI by the functional magnetic resonance imaging (fMRI). ^[14] However, the results are simply for the healthy controls, and the brain activation mechanisms during the ME/MI of the upper limbs in stroke patients are unclear. Therefore, this study continues to use fMRI to explore the activated brain network during ME/MI in healthy human controls and patients recovered from stroke (stroke within 3 months).

Methods

Subjects

Twelve patients (7 males; a mean age of 53.17 years [Supplementary Table 1]) with first-ever subcortical stroke were prospectively recruited. The criteria for selecting patients included initial disease occurrence and obvious hemiplegia due to cerebral infarction or cerebral hemorrhage. The specific inclusion criteria included the duration of motor dysfunction ≥1 month; the extension of the ipsilateral wrist >10; the extension between the thumb, the metacarpophalangeal joint, and the interphalangeal joint of at least two fingers >10; and that extension can be repeated three times/min. Exclusion criteria included a persistent language deficit, significant renal or liver disease, carotid artery stenosis/occlusion, neglect/inattention, treatment with selective serotonin reuptake inhibitors or benzodiazepines, a large area of infarction or massive bleeding, and bilateral hemisphere damage. Twelve age-matched controls (6 males; a mean age of 56.67 years [Supplementary Table 2]) were recruited through a local advertisement. The controls had no history of medical disorders and were not taking regular medication. All the controls were right-handed. Written consent was obtained from each participant, and the protocol was approved by the Ethics Committee of the Third Military Medical University. For each participant, mental status was assessed by the Mini-Mental State Examination, MI performance was evaluated by the Movement Imagery Questionnaire-Revised, Second Edition, and those controls who were unable to adequately perform MI were excluded from the study.

Experimental design

All the controls experienced four sequential runs in this order: Unaffected left-hand ME; left-hand MI; affected right-hand ME; and then right-hand MI. The ME procedure was to press the thumb and index finger together at a frequency of 1 Hz. As the patient group had finger movement problems in the affected hand, they were asked to try their best to pinch between the thumb and index finger, and the actual pinching frequency was below 1 Hz. The MI procedure was to imagine the same movements without actually performing them. A diagram of an idealized experiment is illustrated in [Figure 1]. Each run included 5 blocks, each lasting for 1 min. Within each block, a 10 s instruction period preceded a 30 s resting baseline period, followed by a 30 s ME (MI) period. During the ME run, the screen presented a picture of the corresponding finger movement at a frequency of 1 Hz. During the MI session, the screen presented an arrowhead; the left arrow directed the participant's attention to the left hand, while the right arrow directed the participant to the right hand. During the rest period, black cross picture on the center of the screen reminded the participants to place their hands on the sides of their bodies and breathe quietly. The stimulus presentation and behavior recordings were conducted with E-prime software (company and location). A Data Glove (5DT) was used to monitor the participants' behavior during the whole process of the experiment. If the participants did not perform in accordance with the requirements during ME or they had obvious finger movement during MI, the experiment would be stopped. Before the fMRI experiment, the participants received task training twice, for 1 h each time.

Figure 1: Example diagram of the experiment (a) motor execution (b) motor imagery. Each participant underwent four 5-min runs. Each run included five identical 60-s blocks, and the 60-s blocks comprised a 30-s rest period and 30 s of motor execution (or motor imagery). (c and d) image showing how to perform motor execution with the right hand (c) and the left hand (d)

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Data acquisition

The data were collected on a 3.0T MRI scanner (Trio, Siemens Medical Erlangen, Germany). All fMRI scans were performed using a T2*-weighted gradient echo sequence, a standard birdcage radio-frequency coil, and the following parameters: Repetition time (T_R ) = 2000 ms, echo time (T_E ) = 30 ms, flip angle = 90°, 64 × 64 voxel matrix, field of view (FoV) = 220 mm, 27 contiguous axial slices acquired in interleaved order, and thickness = 4.0 mm. High-resolution T1-weighted structural images were also obtained, using the three-dimensional gradient-echo technique pulse sequence, under these parameters: T_R = 1900 ms, T_E = 2.52 ms, TI = 1100 ms, flip angle = 15, 256 × 256 voxel matrix, FoV = 240 mm, 176 contiguous axial slices, and thickness = 1.0 mm. During the scan, the participants were asked to lie on the scanner and keep quiet and still.

Data preprocessing

The SPM8 software (http://fil.ion.ucl.ac.uk.spm/) was used to analyze the data. All the original images were reoriented and realigned, and those whose head motion was >0.5 mm or rotation was >0.5° were excluded from the following analysis. All functional volumes were realigned to the first functional volume, and then all realigned images were normalized into a standard stereotaxic space using an echo planar imaging template delivered with SPM and spatially smoothed using a Gaussian kernel with an FWHM of 6 mm.

Statistical analysis

After conducting the data preprocessing, the modeling analysis of the individual data showed the specific activation of brain function during ME/MI. The SPM-8 analysis software separately performed the single-sample t-test for the two groups' brain function results during the ME/MI. To detect the differences in brain activation between ME/MI and the rest period, we also performed a one-sample t-test-group analysis. In addition, we used gender and motion imagination score as covariates to perform the covariance statistical analysis. The SPM(t)s were thresholded at P < 0.01 (false discovery rate correction), voxels ≥20.

Interestingly, the BOLD signal was different between the young and old groups while they were performing the same task. As a result, we conducted a two-sample t-test (P < 0.001, uncorrected) to (1) compare the left- and right-hand ME between the old group and the young group and (2) compare the left- and right-hand MI between the old group and the young group.

Results

Motor execution between the control and patient groups

The activation pattern was found to be extremely similar during ME under the visual guidance between the groups. The main activated brain areas comprised the bilateral premotor cortex (PMC) and the supplementary motor area (SMA), the primary motor cortex (M1), the cerebellum, the thalamus, the superior and inferior parietal lobe, the fusiform lobe, the superior frontal lobe, the putamen, and the superior temporal lobe [Figure 2]a, b, e, f, and [Table 1], [Table 2].

Figure 2: The activation of brain function in the control and patient groups under different conditions: (a) control left-hand motor execution; (b) control right-hand motor execution; (c) control left-hand motor imaging; (d) control right-hand motor imaging (e) patient left-hand motor execution; (f) patient right-hand motor execution; (g) patient left-hand motor imaging; and (h) patient right-hand motor imaging. All the voxels were significant at P < 0.01, corrected for false discovery rate of the whole brain

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Table 1: The activated brain areas during motor execution and motor imagery of both hands in the control group

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Table 2: The activated brain areas during motor execution and motor imagery of both hands in the patient group

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The two-sample group analysis [Figure 3]a, b and [Table 3] indicated that there were differences in the activated brain areas during ME between the two groups, despite their similarities. Due to ME with the affected hand or the unaffected hand, the stroke patients had a stronger activation in the brain than the control group, mainly in the ipsilateral precentral gyrus, the postcentral gyrus, the SMA, the frontal gyrus, the parietal gyrus, and the angular gyrus. In addition to the ipsilateral activated brain areas, we observed brain activation in contralateral motor areas such as the precentral gyrus, the SMA, and the parietal gyrus, which was stronger than that of the control group during motor execution in the patients' affected hands. The ME in the unaffected hands of stroke patients demonstrated no difference in brain activation in relation to the control group.

Figure 3: The two-sample t-test group results of the differential contrasts between the healthy control and patient groups (a) left-hand motor execution; (b) right-hand motor execution; (c) left-hand motor imagery; and (d) right-hand motor imagery. Stronger activation for the control group versus the patient group is shown in red and for the patient group versus the control group in blue

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Table 3: Areas differentially activated during motor execution in the control versus the patient group

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Motor imagery between the control and patient groups

For a whole-brain analysis examining the BOLD response to the MI, brain regions were found to be similarly activated in both the two groups [Figure 2]c, d, g, h and [Table 1], [Table 2]. As shown in [Figure 2]c and d, increased activation was found in M1, the SMA and PMC, the cerebellum, the frontal lobe, the parietal gyrus, and the parietal gyrus.

In our study, we mainly focused on the difference in MI between the two groups, which is shown in two-sample t-test group results [Figure 3]c, d and [Table 4]. During the movement imagination of the y hand (left hand), the ipsilateral brain activation in the patient group was significantly lower than that in the healthy group, particularly in the left precentral gyrus, the postcentral gyrus, the frontal gyrus, and the parietal gyrus. The contralateral, uninjured, and right parietal gyrus in the patient group showed a stronger activation. During the MI of the affected hand, the activation in the patient group was significantly weaker than that in the healthy group, including the uninjured, ipsilateral areas of the brain such as the postcentral gyrus, the frontal gyrus, the SMA, and the cerebellum. On the contralateral side, the activation in the parietal gyrus and frontal gyrus was also weaker than that in the healthy controls.

Table 4: Areas differentially activated during motor imagery in the control versus the patient group

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Discussion

The present study used fMRI to investigate the neural mechanisms underlying ME and MI in stroke patients. First, we found that brain activation in the ipsilateral primary motor areas of the stroke patient group appeared to be greater than that in the control group during ME, particularly in the precentral gyrus, the postcentral gyrus, the SMA, and the cerebellum. This finding indicates that ipsilateral inhibition is reduced in stroke patients during ME. Second, regardless of whether the MI was of the affected hand or the unaffected hand, the ipsilateral brain activation of the patient group was weaker than that of the healthy group, while the contralateral activation was greater than that of the healthy group. This suggests that despite the disease in the patient group, the brain activation pattern is better than the control group during MI, the contralateral brain is more easily activated, and the ipsilateral brain regions are more easily inhibited. In addition, the MI of the affected hand in the stroke patients was not significantly different from that of the unaffected hand, which implies that MI may be used to improve injured brain areas, activate brain areas, and help with the rehabilitation of stroke patients. Third, these results indicate that the damage to brain structure is related to the brain function activation in stroke patients.

Motor execution

During ME, the main motor brain regions had a stronger activation in the patient group than in the controls, which was consistent with the other findings. ^[15],[16] In patients, the attempt to overtly move the left (paretic) wrist recruited the same areas plus a number of additional regions. These included, in particular, the anterior premotor and prefrontal cortices and the extended parietal cortices. In general, activation was more bilateral in patients, including activation of the ipsilateral pre- and primary-motor cortices. ^[16],[17] In this study, the ME of the unaffected hand in the patient group showed no significant difference in activation from the control group. In contrast, contralateral brain areas such as the precentral gyrus, the SMA, and the parietal gyrus presented a stronger activation in the patient group than in the control group during ME of the affected hand. These results demonstrate that the attempt to move the fingers activates the motor system of the brain, even just minimal movement. This finding verifies that practice-related improvements in movement performance provide a model for the rehabilitation of patients following stroke. This is similar to the results of other studies. In the unaffected hemisphere, sensorimotor cortex activation was found to be increased in stroke patients when compared with the controls. In partially recovered stroke patients, an intriguing finding related to the movement of the affected hand is the enhanced activation of the contralesional motor network, including the primary sensorimotor cortex. ^{[16],[17],[18]}

During ME of the unaffected hand or affected hand, ipsilateral brain areas showed a stronger activation in the patient group versus the control group. This indicates that ipsilateral inhibition was reduced, which was consistent with the laterality. In the major motor areas, the laterality index in the healthy controls was significantly higher than that in the patient group. This is also consistent with the result of Sharma et al. ^[19] that the hemispheric balance of BA4 activation was significantly less lateralized in stroke patients than in controls.

Motor imagery

In this study, the ME and MI brain activation in both groups were very similar, with large overlapping regions, such as M1, the PMC, and the SMA, which is consistent with the other findings. Previous studies have reported that the same neural networks are activated when movements are mentally practiced, such as during physical practice of the same skills. ^{[20],[21],[22]} MI in our study activated a network of cortical areas [Table 4], which is highly consistent with the previous reports that the lateral and medial premotor cortices and the inferior and superior parietal cortices were activated during MI of simple movements. ^{[23],[24],[25],[26]}

In this study, during MI, the ipsilateral brain activation in the patient group was weaker than that in the healthy group, while the contralateral activation was stronger in the patient group than in the healthy group, regardless of whether the unaffected hand or the affected hand was imagined. This suggests that despite their disease, the brain activation patterns in the patient group during MI were better than those in the healthy controls, and it is thus more likely to activate the contralateral brain and inhibit the ipsilateral brain regions. In addition, there was no significant difference in brain activation in the patient group during MI of the unaffected hand versus the affected hand. Hence, we can conclude that during ME, there is a difference between the unaffected hand and affected hand of the stroke patients, but there is no difference in the brain areas activated by MI. Thus, MI can be used for rehabilitation of stroke patients and may be particularly suitable for stroke patients with early dyskinesia or passive treatment problems. It has been suggested that stroke patients with mental practice can improve motor function in the affected upper limb. ^[27]

It has been reported that a stroke patient can improve the ability to mentally imagine finger movements, taking advantage of the previously idle ventral visual processing stream to imagine finger movements. In particular, the recovery of motor function after a stroke is accompanied by a redistribution of activity within a network of parallel-acting cortical motor areas ^[28] and a reinforcement of the spared area adjacent to the lesion. ^[29] Our results also confirm that nonprimary motor areas, the lingual and fusiform gyri, are active during MI and ME in the patient group and thus play a role in remodeling brain function.

This study indicates that MI can activate brain regions associated with actual ME; thus, MI is expected to enhance neurorehabilitation following stroke. Our data further demonstrate that MI therapy may be beneficial at all stages after stroke. However, our study has some limitations. First, the patient groups are early stroke patients. Second, although we used fMRI technology and discovered that MI can stimulate the brain network, the elasticity function of the brain can remodel the brain function of stroke patients, restoring some motor function, and we did not trace the rehabilitation effect of MI in treating stroke patients. Our next study will expand the research sample size and longitudinally track the additional therapeutic effect of new MI with the traditional treatment methods to further study the neural mechanisms underlying MI for the rehabilitation of stroke patients and help their clinical treatment.

Conclusion

During ME of the unaffected hand, contralateral activation shows no significant difference between the two groups; during ME of the affected hand, the contralateral activation is greater in the patient group than in the control group, and many nonmotor brain areas are activated. This finding indicates that the damaged brain needs to recruit more brain areas to complete the desired action due to motion difficulties resulting from brain damage, confirming the previous view of remodeling brain function. During MI, brain areas show relatively greater activation in the patient group than in the control group, which verifies our previous hypotheses that to achieve the same level as healthy patients, stroke patients may need more and stronger brain activation on the affected side. Because of the remodeling function of the brain, nonmotor brain regions may be involved in the process of MI or ME in stroke patients and play a remodeling role.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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