Here, we investigate the effect of functional occupational therapy combined with assisted active or passive motion on the upper limb function of patients with right hemisphere damage and explore the effect of functional near-infrared spectroscopy on brain function remodeling.
To investigate the effects of functional occupational therapy (FOT) combined with different types of exercise on upper limb motor function recovery and brain function remodeling in patients with right hemisphere damage (RHD) by analyzing functional near-infrared spectroscopy (fNIRS). Patients (n = 32) with RHD at Beijing Bo’ai Hospital were recruited and randomly allocated to receive either FOT combined with passive motion (N=16) or FOT combined with assisted active movement (N=16). The passive motion group (FOT-PM) received functional occupational therapy for 20 min and passive exercise for 10 min in each session, while the assisted active movement group (FOT-AAM) received functional occupational therapy for 20 min and assisted active exercise for 10 min. Both groups received conventional drug therapy and other rehabilitation therapy. Treatment was performed once a day, 5 times a week for 4 weeks. The recovery of motor function and activities of daily living (ADL) was assessed using Fugl-Meyer Assessment upper extremity (FMA-UE) and modified Barthel index (MBI) before and after treatment, and brain activation of the bilateral motor area was analyzed with fNIRS. The findings suggested that FOT combined with AAM was more effective than FOT combined with PM in improving the motor function of RHD patients’ upper limbs and fingers, improving their ability to perform activities of daily living, and facilitating brain function remodeling of the motor area.
Cerebral hemispheric damage can lead to sensory and motor dysfunction of the contralateral limbs1,2,3, negatively affecting patients' motor control, mobility, and functional learning to various degrees4 and therefore imposing heavy burdens on families and society5. For patients with right hemisphere damage (RHD), the speed of recovery is less than satisfactory. However, in most RHD cases, the affected left limbs, being on the non-dominant side of the body, have received insufficient attention from the patient and the caregivers. Given that dysfunction of the upper limbs and hands seriously affects the ability to perform daily activities and quality of life, a more suitable method to improve the rehabilitation effect of upper limb function in RHD patients is needed6,7,8,9,10.
Exercise therapy is an important method to help patients recover their limb function. For the early rehabilitation of patients with brain injury, passive movement (PM) and assisted active movement (AAM) training methods are usually used. AAM entails the activity of specific joints completed through a combination of their own muscle strength and outside assistance11. The key is for the patient to actively participate in assisted rehabilitation. The readiness of the human brain to activate can help stimulate and integrate the motor system in the cycle of motor control. Many studies have shown that AAM can induce neuroplastic changes, thereby leading to increased functional recovery in patients12,13.
Functional near-infrared spectroscopy (fNIRS) is an imaging technique based on optical principles. According to the correlation between the attenuation of light in the tissue and the different concentrations of light-absorbing substances, fNIRS can quantitatively analyze concentration changes in oxygenated hemoglobin and deoxygenated hemoglobin in brain tissue, thereby monitoring the functional activity of the cerebral cortex14. Many studies have shown that fNIRS is an important means of monitoring brain oxygenation and energy metabolism after cerebral hemisphere injury15,16,17. Therefore, fNIRS might be a suitable monitoring method for studying cerebral cortex changes related to upper limb motor function recovery after cerebral hemisphere injury.
The motor signals produced by different sensory input methods and the adjustment states of the sensory cortex are different18,19. The sensory stimuli produced by passive and active movements are closely related to the stability of perception and the ability to build accurate representations of one's environment, which then guide one's behavior20. This study was designed to explore the effects of different modes of exercise on early upper limb rehabilitation and brain activation in patients with cerebral hemispheric injuries by analyzing fNIRS data and to provide scientific strategies for the comprehensive rehabilitation of patients in the future.
The purpose of this study was to investigate the effects of FOT combined with different types of exercise on upper limb function and brain remodeling in RHD patients. We hypothesized that FOT-AAM is more effective than FOT-PM in improving upper limb function and brain activation in RHD patients.
This study was a single-blind randomized controlled trial and was approved by the Ethics Committee of the China Rehabilitation Research Center (CRRC-IEC-RF-SC-005-01) and registered with the Chinese Clinical Trials Registry (MR-11-23-023832).
1. Participants
2. Randomization and allocation
3. Intervention
4. Assessment
5. Statistics
Baseline
From October 2021 to June 2023, we recruited 35 patients, 32 of whom ultimately completed the study; no patients experienced any adverse events during the trial.
Regarding the clinical symptoms of the two groups of patients (Table 1), the average ages of the EG and the CG were 53.19 ± 10.72 and 55.88 ± 12.32 years (P = 0.515), respectively. There were no significant differences in gender, disease type, FMA-UL scores, or MBI scores (P > 0.05). Before the intervention, the FMA-WH scores of all patients in both groups were 0 points.
FMA-UL has high clinical significance and can effectively and reliably assess upper limb involvement in patients with brain injury. The FMA-UL has a total of 33 upper limb assessment items, and each unidirectional score is assigned as 2 points for full completion, 1 point for partial completion, and 0 points for no completion. The total possible upper limb movement score is 66 points. As a subcategory of the FMA-UL, the wrist-hand scale (FMA-WH) has 12 items, with a total possible score of 24 points.
The results of repeated measures analysis of variance showed that the main effect of the group on FMA-UL score was significant, F = 5.564, p = 0.030, ɳ2p = 0.214; the main effect of time was significant, F = 34.716, p < 0.001, ɳ2p = 0.831; the interaction effect of group and time was significant, F = 5.554, p = 0.030, ɳ2p = 0.256. (Table 2)
The main effect of the group on the FMA-WH score was significant, F = 8.817, p = 0.006, ɳ2p = 0.227; the main effect of time was significant, F =13.357, p = 0.001, ɳ2p = 0.308; The interaction effect between time and group was significant, F = 8.817, p = 0.006, ɳ2p = 0.227. (Table 2).
The modified Barthel index is widely used to assess the ability to perform daily activities and measures a person's ability to perform ten such basic activities. The total possible score on the Barthel index is 100 points, and the higher the score is, the stronger the patient's ability to perform activities of daily living.
The main effect of the group on the MBI score was significant, F = 8.512, p = 0.007, ɳ2p = 0.221; the main effect of time was significant, F = 588.559, p < 0.001, ɳ2p = 0.952; the interaction effect between group and time was significant, F = 10.425, p = 0.003, ɳ2p = 0.258. (Table 2).
The integral value is the integral of the blood oxygen signal during the execution of the task and reflects the magnitude of the hemodynamic response during the task. The centroid value is the time (s) shown by the vertical line of the center of the blood oxygen signal change area during the entire task period and is an indicator of time-course changes throughout the task, representing the speed of the hemodynamic response27.
There was no significant difference in the integral or centroid values between the two groups before (Figure 5A) the intervention (P > 0.05). After the intervention, the integral value of the right hemisphere of the subjects in the CG was 0.20 ± 0.32, the integral value of the right hemisphere of the subjects in the EG was -0.06 ± 0.24, and there was a significant difference in the overall means of the two groups (t=-2.489, d=0.92, P = 0.020, P < 0.025 is considered statistically significant) (Table 3). After the intervention, the integral value of the left hemisphere of the subjects in the CG was 0.18 ± 0.32, the integral value of the left hemisphere of the subjects in the EG group was -0.04±0.26, and there was no significant difference in the overall means of the two groups (t=-1.975, P=0.059, d=0.75). There were no significant differences in the centroid values between the two groups after the intervention (P > 0.025) (Figure 5B).
Figure 1: Recruitment flow chart. A total of 35 subjects were recruited, of which 2 subjects did not meet the requirements and 1 subject dropped out due to the epidemic, and 32 subjects were finally included. Please click here to view a larger version of this figure.
Figure 2: Upper limb rehabilitation training with different movement modes. (A,B) EG performing active hand rehabilitation training. (C) CG performing passive hand rehabilitation training. Please click here to view a larger version of this figure.
Figure 3: Arrangement and location of light beams. A red circle represents a light source, a blue circle represents a detector, and the path of the beam is shown between them. Please click here to view a larger version of this figure.
Figure 4: Task paradigm. A rest (15 s)-task (30 s)-rest (15 s) was used as a test unit and repeated 5 times in total. Please click here to view a larger version of this figure.
Figure 5: Scatter plots showing the distributions of the centroid values and integral values of the right hemisphere in the two groups of patients. (A) Before the intervention. (B) After the intervention. Please click here to view a larger version of this figure.
Variable | PM (n = 16) | AAM (n = 16) | p value |
Gender (male/female) | 9/7 | 8/8 | 1 |
Age in years (mean ± SD) | 53.19 ± 10.72 | 55.88 ± 12.32 | 0.515 |
Type (hemorrhagic/ischemic) | 9/7 | 6/10 | 0.479 |
Table 1: Subject characteristics. FMA: Fugl-Meyer Assessment; MBI: Modified Barthel Index; PM: passive motion; AAM: assisted active movement; FOT: functional occupational therapy.
Assessment Indicators | Main Effect (Group) | Main Effect (Time) | Interaction Effect (Group x Time) | ||||||
F | P-values | η²p | F | P-values | η²p | F | P-values | η²p | |
FMA-UL | 5.564 | 0.03 | 0.214 | 34.716 | <0.001 | 0.831 | 5.554 | 0.03 | 0.256 |
FMA-WH | 8.817 | 0.006 | 0.227 | 13.357 | 0.001 | 0.308 | 8.817 | 0.006 | 0.227 |
MBI | 8.512 | 0.007 | 0.221 | 588.559 | <0.001 | 0.952 | 10.425 | 0.003 | 0.258 |
Table 2: Results of analysis of repeated two-way ANOVA conducted on GROUP, TIME, and interaction effect on FMA-UL, FMA-WH, and MBI.
Assisted Active Movement Group | Passive Movement Group | |||||
mean ± SD | mean ± SD | t value | P value | Cohen’s d | ||
Integral value | Left | -0.04 ± 0.26 | 0.18 ± 0.32 | -1.975 | 0.059 | 0.75 |
Right | -0.06 ± 0.24 | 0.20 ± 0.32 | -2.489 | 0.02 | 0.92 | |
Centoid value | Left | 13.03 ± 10.45 | 11.54 ± 9.13 | 0.396 | 0.695 | 0.15 |
Right | 11.04 ± 12.00 | 12.58 ± 10.98 | -0.351 | 0.728 | 0.13 |
Table 3: Comparison of fNIRS data between the two groups after the intervention.
In this study, by using near-infrared spectroscopy, we explored the effect of FOT combined with upper limb functional training in different exercise modes on the early rehabilitation of RHD patients. FOT helps the patient passively move the stiff upper limbs to facilitate subsequent training. The key is that the healthy hand leads the affected hand to perform purposeful, important, and practical functional tasks, use real-life objects, and simulate real scenarios as much as possible28. This can stimulate the patient's enthusiasm for treatment and maximize the patient's active movement. The most crucial point of AAM is that the patient's movement is driven by the unaffected limb and hand, while the affected limb and hand make a spontaneous active attempt, which is the most important feature that distinguishes it from passive movement. The rehabilitation devices give patients real-time visual and tactile feedback and complete a closed loop between the central nervous system and the periphery in rehabilitation training29.
There are no complex techniques involved in training for the rehabilitation task, but there are numerous caveats to consider when evaluating patients with fNIRS. To ensure a good fNIRS signal and prevent motion artifacts from interfering with test results, we usually place a head holder on the table in front of the subject. We adjust the height of the table so that the subject's chin rests on the head holder without causing discomfort. This helps to reduce head sway during movement. In addition, skin oil on the scalp will affect the optical signal; accordingly, we wipe the oil from the patient's head with oil-absorbing paper before the experiment to ensure the signal quality. Based on previous experience, we have also found that reducing the influence of natural light and sound improves the collection of fNIRS signals; therefore, we collect all data in a dark and quiet environment30.
Previous studies have shown that MT can effectively improve finger flexibility after stroke 31, especially for the upper limb rehabilitation of subacute patients32, and therefore shows great promise in restoring motor function and improving the ability to perform daily activities after cerebral hemisphere damage33,34,35,36. When a patient moves their unaffected arm, an optical illusion formed by a mirror is considered by the patient to be the movement of their affected hand, which increases the activity of their visual and somatosensory cortical areas, thereby enhancing the patient's attention and reducing the possibility of unilateral neglect37,38. In this way, the patient can consciously choose to use the affected limbs more often39. On the basis of traditional MT, we directly provide somatosensory stimulation and visual feedback to the affected limb through the AAM device, which reduces the unpleasant feeling caused by the asynchrony of proprioception of the affected hand and vision40, thus demonstrating broader therapeutic potential than conventional MT. Our training equipment has a simple operating procedure and a strong safety profile, with the option to stop the training immediately by clicking the close button to avoid emergency situations that may occur during the test. In addition, some studies have demonstrated that MT can promote the normalization of hemisphere balance after stroke by regulating the excitability of M1. In follow-up studies, we will use fNIRS to evaluate the resting-state functional connectivity of the cerebral cortex to verify the cerebral hemisphere changes in RHD patients further after treatment41.
This study has several limitations. First, the task paradigm chosen for the near-infrared spectroscopy test is passive, whereas brain activation may occur more in active movements. Thus, the task paradigm of active attempts may be more suitable than passive movement. Second, we monitored only the M1 area, but MT also increases neural activity in areas involved in attention allocation and cognitive control, which can promote the recovery of motor function by increasing the cognitive role in motor control42; therefore, monitoring prefrontal hemodynamics may also be necessary. In addition, due to the large number of treatment plans for the inpatients, only 10 min of hand rehabilitation training was performed every day. In the future, the training time should be extended to better explore the rehabilitative effect. Follow-up studies are needed to observe the long-term effect of this training. In the future, large-sample multicenter studies are expected to provide the most suitable rehabilitation strategies for early RHD patients.
The authors have nothing to disclose.
This study was supported by the Fundamental Research Funds for Central Public Welfare Research Institutes (2019CZ-11) and the Project of China Rehabilitation Research Center (number: 2021zx-Q5).
Hand Active Passive Rehabilitation Trainer | Soft Robot Technology Co., Ltd. | H1000 | FOT-AAM group training/FOT-PM group training |
Near-Infrared Brain Functional Imaging System | Shimadzu (China) Co.,Ltd. | LIGHTNIRS | Assessment |