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INTRODUCTION
Parkinson’s Disease (PD) is a chronic neurological and progressive disease resulting in the death of dopaminergic cells in the substantia nigra1. The basal ganglia (BG) are responsible for motor sequencing, motor skills, complex actions, modulation of higher-order cognitive functions, and mood regulation, and dopamine plays an important role in preserving these functions2. The principal manifestations of PD are motor dysfunctions such as bradykinesia, resting tremors, rigidity, and postural instability3. During the progression of the disease, non-motor symptoms may develop, such as cognitive and psychological decline, speech difficulties, sleep disorders, constipation, and erectile and urinary dysfunctions4. Even though treatments with pharmaceutical therapies can ease PD-related symptoms, in later stages of the disease these medications are prescribed in higher dosages, leading to unwanted side effects5 and postural instability, however, the therapeutic effects are still unclear6. Non-pharmaceutical therapeutic interventions, such as rehabilitation can also help to maintain or improve motor symptoms, balance, gait, and functionality7. The main objective of rehabilitation for these individuals is to minimize the primary and secondary motor symptoms of the disease, which consequently helps the patient maintain independence, enhances the performance of daily living activities, and improves quality of life8.
It is well-established that rehabilitation has a positive role in maintaining motor performance in people with PD9-12. The introduction of Physical Therapy (PT) showed benefits in strength13, functional mobility14, gait-related mobility, such as speed and step size15,16, and balance17,18.
Among the various rehabilitation possibilities, Virtual Reality (VR) is currently used as a tool to improve both the motor and cognitive functions of people with PD19-21. It is important to emphasize that VR can also enable the individual to learn new complex functional tasks that may involve planning, including daily activities such as riding public transport, shopping in the market, and driving22. Enhanced engagement, motivation, and attention are among the important potential benefits of VR and can contribute to increasing the interest of individuals in rehabilitation and increasing the intensity of practice23,24. Although there are some benefits from using VR alone in people with PD, recent studies have encouraged combining interventions and technologies as a promising rehabilitation option25,26.
Non-invasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS), are neuromodulatory interventions. Considering combined interventions, these techniques are currently being used to treat PD symptoms27-29 and can be combined with VR practices25. tDCS is a NIBS with low-frequency electrical stimulation, that can alter neuronal activity depending on the polarity of the stimulation, using electrodes placed on the scalp30. The electrodes used in the tDCS stimulation have anode and cathode polarities which change the resting state of the membrane cells of the surrounding region, which can modulate and potentially stimulate brain networks, depending on the target area and the polarity of the stimulation26,31. tDCS has already been used as a treatment to control motor symptoms of Parkinson’s Disease and other movement disorders, such as dystonia32, Parkinson’s Plus33, and Cerebellar Ataxia34.
A large number of studies that involved healthy individuals and people with other neurological pathologies showed better and longer-lasting improvement in motor performance when tDCS was applied combined with other types of rehabilitation tools, such as treadmill training, working memory training, physical exercises, and intensive speech therapy, among others35-38.However, despite the potential for combining interventions, no studies have investigated the combined effects of tDCS and VR to promote motor performance in individuals with PD.
It was organized a protocol using tDCS and VR to identify the possible benefits of this combined therapy. Hence, we evaluated individuals with PD who were divided into 2 groups (one group performed a VR task with active tDCS (Active Group) and the other group used the same VR task, but with sham tDCS (Sham Group). Both groups performed a coincident timing task using software on a computer.
In this trial, we hypothesized that all participants with PD would present improved performance after practicing the coincident timing task in a non-immersive VR using upper and lower limbs and that individuals with tDCS stimulation would present greater improvement when compared with the sham tDCS. Moreover, we expected that all participants would enjoy practicing the VR task, identified using an enjoyment scale. If these hypotheses were confirmed, the results of the present study would be relevant for the treatment of people with PD.
METHODS
The trial was carried out according to CONSORT guidelines for Pilot and Feasibility Studies https://www.equator-network.org/reporting-guidelines/consort-2010-statement-extension-to-randomised-crossover-trials/.
Design
This is a randomized, placebo-controlled, and triple-blind study conducted from May 2019 to February 2020. Participants who met the eligibility criteria were randomly assigned to 2 groups: Active tDCS + VR and Sham tDCS + VR.
Ethics committee and regulatory approval
This research was approved by the Ethics Committee of the University of São Paulo, with registration number CAAE: 02908218.0.0000.5390. Resolution 466/2012 of the National Health Council of 10/10/1996, which regulates research involving human beings, and the Declaration of Helsinki (1996) were respected. Data were stored electronically in databases with restricted and secure access. Any severe side effects during the study were reported to the emergency services in the area.
Randomization and Blinding
Randomization was performed through a blinded electronic security file used to assign individuals to the groups. The investigator TDS was responsible for the computer-generated random assignment list, arranging patients in Groups (1 and 2). The participants, researchers who performed the intervention, and statisticians were blinded to the participants’ group until the end of the data analysis. To ensure adequate blinding, participants were given codes and separated for the allocation process by a different investigator. Before each stimulation session, the researcher responsible for the stimulation received a code that programs the tDCS device to deliver 20 min of active or sham stimulation.
Participant Recruitment
Fifty-four individuals with PD, previously diagnosed by a neurologist, participated in this study. They were recruited through social media, such as Facebook, Instagram, and WhatsApp groups. The researchers responsible for the study sent flyers through social media to advertise the study, and potential participants contacted them to establish a day to apply the intervention.
Inclusion Criteria
Participants were included if they: (a) had a previous diagnosis of PD confirmed by a specialist; (b) agreed to participate in the study with a term signed by themselves; (c) did not use a wheelchair; (d) was able to stand without any type of aid (such as canes and crutches) (Modified Hoehn & Yahr Scale from 1 to 4); (e) had good visual and auditory acuity; (f) presented no other pathology of neurological, orthopedic, or cognitive origin (observed by the Mini Mental State Examination MMS Escale); and (g) did not use Deep Brain Stimulation (DBS) or have any contraindications to tDCS.
Exclusion Criteria
Patients were excluded from the study if they: (a) were unable to understand the proposed VR task –assessed after 2 minutes of practice, or (b) dropped out of the protocol during practice due to fatigue or major imbalance.
Primary outcome (Absolute and Variable Error)
The MoveHero game verifies two important movement errors: 1) absolute error (AE), which demonstrates the accuracy of the movement, and 2) variable error (VE), which identifies the precision of the movement39. The specifications of the instrument will be examined below.
Instruments
MoveHero
In the current study, we used a platform called MoveHero, available for free use in Portuguese https://movehero.com.br/ and English https://movehero.com.br/en/. The patient was required to access the Internet to create their account, insert their name and email, and create a password (all data were collected in the software system and only the principal investigator had access). The platform presents different levels of difficulty, so after the participants had connected to the platform, the researcher directed them to the protocol developed for this research, which will be described below.
Presented by Martins et al.40, MoveHero is considered a coincident timing task and presents several spheres falling down the computer screen, with a musical rhythm to increase engagement. The participant is positioned in front of a computer and when the game starts the webcam captures their movements, which are represented on the computer screen by an avatar. The goal of the game is to intercept all falling spheres, using upper or lower limbs, at the exact moment the spheres reach their specific target at the bottom of the computer screen. When the player uses the lower limbs they execute an abduction of the hips to reach the targets and when they use the upper limbs they execute a wave movement of the arms. The game presents four columns with fixed parallel targets allocated at two height levels (e.g., two on the left - targets A and B; two on the right – targets C and D). The game also provides sensory feedback (visual – hit and miss feedback; auditory – anticipatory and delay error) – If the individual intercepts the sphere correctly, the game presents feedback by the sphere changing the color of the target to blue, with little stars around it (hit information). On the other hand, if the participant does not intercept the sphere correctly, the sphere changes color to red and the letter X appears inside the target (missing information) together with a sound indicating an error.
Software Score
During the game, the participant can follow their score, determined by the number of spheres hit (i.e., the information from each sphere hit appears in the bottom left side of the screen at all times) and at the end of each game, the participant receives feedback with their total score (when the game is finished a total score appears in the middle of the computer screen).
Intervention with tDCS
Active tDCS and Sham tDCS were performed in a single session combined with the VR task. The frequency used was 2mA and the stimulation intensity was programmed to 100%. The electrode corresponding to the positive side (anode) was positioned in the M1 cortical area (primary motor cortex) in the dominant hemisphere, and the negative electrode (cathode) was positioned in the contralateral supraorbital area. For the sham stimulation, the electrodes were placed in the same position and an active current was initiated with ramping up and down for 30 seconds to simulate the real stimulation. A saline-soaked 35 cm2 (5×7cm) sponge with electrodes was placed on the patient’s scalp and secured with adjustable rubber straps. The sponge placement follows the 10–20 EEG system. All the patients were aware of the side effects every day, according to international safety guidelines41. The device used was NeuroConn’s DS-Stimulator, which allows blinding of individuals and researchers.
Procedures
The patients were contacted by telephone and asked if they were interested in participating in the study. If they agreed, they received the Free and Informed Consent Form to fill out, and the inclusion criteria were checked. The researcher applied a brief anamnesis to collect personal and sociodemographic data. After the anamnesis, the researcher applied the scales, and then the tDCS equipment was prepared. First, the circumference of the skull it was measured with a tape measure, and then the researcher asked the patient to indicate their dominant cerebral hemisphere (for correct positioning on the skull). The tDCS was administered by an experienced professional and according to pre-established methods of management in the adult population41. Positioning was the same for the active and sham tDCS, and two square sponges soaked in saline were placed on the skull and fixed with a plastic band. The active (anodic) tDCS was performed with electrodes of 25-35cm2, an intensity of 2mA, a rise and fall ramp of 30 seconds, and a density of 0.057mA/cm2. The anodic electrode was positioned in the M1 area in the dominant hemisphere, which was previously observed by Fregni et al.42 who reported that it could be an important target for brain stimulation in individuals with PD. Lang et al.43showed that anodic tDCS in the primary motor cortex induces an increase in basal ganglia activity. The cathode electrode was positioned in the contralateral supraorbital area. The sham tDCS had the same procedures as the active, but the current was interrupted after 30 seconds of stimulation. This configuration ensured that the stimulus would be stopped after generating a considerable stimulus, while the other features of the intervention were maintained.
After correct positioning of the tDCS equipment, a protocol-blind researcher configured the equipment according to a code (previously provided by a 3rd researcher, who established the codes that would be active and sham) and induced the initial stimulus of 5 minutes (at rest, while the patient was sitting). Meanwhile, another blind researcher placed the notebook (14 inches) on a table (the participant was 1.5 m away from the screen) adjusted according to the patient’s height (the taller the individual, the higher the placement of the computer), and set the game to launch. Immediately after the setup, the researcher explained the game to the patient. It is important to emphasize that the participants had no previous contact with the MoveHero game. The researcher started the MoveHero game and remained behind the patient to avoid any imbalance.
The VR task was performed in 2 attempts (4 minutes each) totaling 8 minutes of practice. In the first 4 minutes, the participants used the upper limbs to intercept the spheres (4 targets) (Figure 1). In the final 4 minutes, the participants used the lower limbs (for the 2 most proximal targets - the distal targets were too far away to be reached with leg abduction) (figure 2). To play with the lower limbs, the researcher angled the computer screen so the camera could focus only on the patient’s lower limbs. The players’ heart rate was monitored throughout the protocol and if they were unable to perform the VR task for the whole 8 minutes of practice (due to fatigue or severe postural instability), the game was interrupted, and the patient rested for a few minutes. They were then asked if they were willing to continue playing; if not, the patient was excluded from the study, and if so, the researcher continued the game from the moment they had previously stopped.
After 8 minutes of tDCS + VR, participants received 5 minutes of final resting stimulus, totaling 18 minutes of stimulation (approximately 20 minutes), which is the time used in studies with anodic tDCS in people with PD by Schoellmann et al.29 and Doruk et al.44 After the end of the session, participants were asked about the presence of adverse effects and assigned a score for the game ranging from 0 to 4, with 0 indicating a “Very Boring” game, 1 “Boring”, 2 “Somewhat Fun”, 3 “Fun”, and 4 “Great Fun”.
Data Analysis
We considered the Absolute Error (AE) and Variable Error (VE) as dependent variables. The MoveHero game performs the measurements in milliseconds to demonstrate the movement accuracy and identify the precision of the movement, respectively. The hit attempts of the targets in the game MoveHero were transformed into 3 blocks of attempts, by dividing the total of 4 minutes into 3 (1.3 minutes in each Block) to evaluate if there was an improvement from the first Block (B1) to the second Block (B2) and the third Block (B3). In this way, we were able to evaluate whether the first attempts were better than the later ones. Multivariate Analysis of Variables (MANOVA) was applied to compare active and sham tDCS, with repetitive measures for “Blocks’’ and “Limbs” (Upper Limbs and Lower Limbs). Values were considered significant with p<0.05. The data in the graphics are represented as mean and standard error. Partial Eta squared (η2) was reported to measure the effect size and interpreted as a small (effect size >0.01) medium (effect size >0.06) or large effect (effect size >0.14). The statistical package used was SPSS (IBM Corporation, Armonk, NY, United States) version 20.0.
RESULTS
Table 1 presents the mean values for age, weight, height, Mini BESTest, BBS, Mini-Mental Test, and MDS-UPDRS, as well as the dispersion values. The inferential analysis showed that the groups were homogeneous in these variables. There were differences between the total value of the MDS-UPDRS scale, in the Upper Limbs section of the UPDRS, which consists of the separate analysis of items 20 to 25 of the scale45 and subsections of the UPDRS (Part III, IV A, and VI C) (Table 1).
Initially, 68 participants agreed to participate in the study and underwent detailed screening using the eligibility criteria. A total of 54 individuals (20 women and 34 men) participated in the study, 25 in the active tDCS (mean age = 62.2 ± 11.1 years) and 28 in the sham tDCS (mean age = 66.3 ± 7.2 years). On the Hoehn & Yahr scale, 2% of patients were in stage 0 (1 patient in the sham tDCS), 31 patients in stage 1 (57%) (18 - active tDCS 69%; 13 - sham tDCS 46 %), 11 patients in stage 2 (20%) (4 - active tDCS 15%; 7 - sham tDCS 25%), 8 patients in stage 3 (15%) (3 - active tDCS 12%; 5 - sham tDCS 18%), and 3 patients in stage 4 (6%) (1 - active tDCS 4%; 2 - sham tDCS 7%).
Anti-Parkinsonism Medication
Table 2 presents the anti-parkinsonian drugs that the patients used. The medications observed were Levodopa (L-dopa), COMT Inhibitors, Anticholinergics, Cannabidiol Oil, MAO-B Inhibitors, Dopamine Agonists, Amantadine, and Antidepressants. A total of 50 of the 54 patients were taking Levodopa (L-Dopa) medication (93%) (25 - active tDCS 96%; 25 - sham tDCS 89%).
MANOVA analysis showed significant effects for Groups [Wilk’s lambda: 0.773; F2, 50= 7.34; p= 0.002, ηp2= 0.23, op= 0.92], Limbs [Wilk’s lambda: 0.663; F2, 50= 12.7; p< 0.001, ηp2= 0.34, op= 0.99], and Blocks [Wilk’s lambda: 0.523; F4, 48= 11; p< 0.001, ηp2= 0.48, op= 1.0]. There were no significant effects for the Positions factor or significant interactions between factors. Separate ANOVAs are presented below.
Motor Performance
Absolute Error - AE
Significant main effects were found between Groups [F1, 51 = 4,43; p = 0.040, ηp2 = 0.08, op = 0.54], Limbs [F1, 51 = 17.72; p <0.001, ηp2 = 0.26, op = 0.98] and Blocks [F2, 102 = 9.0; p <0.001, ηp2 = 0.15, op = 0.96]. This result indicates that all groups presented improved performance with practice, verified through the improvement in the absolute errors between blocks. The active tDCS significantly improved the absolute error from Block 1 (m = 544 ms) to Block 3 (m = 450 ms; p = 0.006), and from Block 2 (m = 518 ms) to Block 3 (m= 450 ms p = 0.006). The sham tDCS significantly improved the absolute error from Block 1 (m = 650 ms) to Block 2 (m = 571 ms; p = 0.015) and from Block 1 to Block 3 (m = 565 ms; p = 0.009). Moreover, the active tDCS had a lower overall absolute error (m = 505 ms) than the sham tDCS (m = 596 ms) and this difference was more evident in the lower limb (i.e., the active tDCS showed a lower absolute error with the Lower Limbs when compared to the sham tDCS (p = 0.05), but not with the Upper Limbs.
Variable Error - EV
Significant main effects were found in the Groups [F1, 51 = 11,80; p = 0.001, ηp2 = 0.18 op = 0,92], Limbs [F1, 51 = 23,3; p <0.001, ηp2 = 0.31, op = 0.99], and Blocks [F2, 51 = 21; p <0.001, ηp2 = 0.29, op = 1.0]. This result indicates that the active tDCS presented a lower overall variable error (453 ms) when compared to the sham tDCS (576 ms), with a significant interaction between Limbs and Blocks [F2, 51 = 3.2; p = 0.047, ηp2 = 0.60, op = 0.60]. The active tDCS showed a lower variable error with Upper Limbs (p = 0.010) and Lower Limbs (p = 0.003) when compared to the sham tDCS. Regarding the Blocks, the active tDCS significantly improved the variable error from Block 1 (m = 501 ms) to Block 3 (m = 389 ms; p <0.001) and from Block 2 (m = 470 ms) to Block 3 (p = 0.003). The sham tDCS significantly improved the variable error from Block 1 (m = 652 ms) to Block 3 (m = 534 ms; p <0.001) and from Block 1 to Block 2 (m = 543 ms; p< 0.001).
Enjoyment
The chi-square test did not present significant results for the Enjoyment score when comparing groups. Most participants within the two groups classified the game as “fun” or “great fun” (94.4%). Only 5.6% of the sample rated the game as “somewhat fun” and no patients rated the game as “boring” or “very boring”.
DISCUSSION
This randomized clinical trial assessed the effectiveness of a single tDCS session on the performance of a VR task in people with PD and our results partially confirmed our hypothesis. All participants (active and sham tDCS groups) with PD presented improved performance with practice using the upper and lower limbs in a VR task and the active tDCS presented better improvement when compared with the sham tDCS, as hypothesized. However, this difference was more evident in the practice with the lower limbs. Moreover, all participants enjoyed practicing the VR task, rating the game as “fun” or “great fun”. These results will be and more fully examined below.
Performance during Virtual Reality
In the present study, both groups showed improvement in performance in the timing coincident task. The active and sham tDCS demonstrated significant differences, with improvement in performance between Blocks for the AE (accuracy) and for the VE (precision), indicating positive use of the VR task among individuals with PD. Several studies have used VR as an alternative for rehabilitation, finding positive results for motor function46,47, balance and coordination48,49, cognitive function, mental health50-52 and increased UPDRS scores51.
The performance improvement may probably be directly related to the various benefits that VR provides, such as the offer of continuous feedback throughout the practice of the game, grading of training intensity, increasing visual, sensory, and auditory feedback, and the possibility of stimulating motor and cognitive aspects with a motivational and engaging environment53.
VR can be an effective tool for the rehabilitation of patients with neurological diseases, by promoting experiences and challenges in a personalized way, since they perform the tasks repeatedly, with continuous feedback and motivation54,55. Thus, we agree with Dias et al.38 that Repetition, Feedback, and Motivation could be the three main factors in improving performance using a VR task. The VR game provided positive feedback and motivational tasks (using music and colored objects). Considering feedback, the participant hits the target, promoting an engaging environment, and maintaining player motivation and participation, which may have contributed to the progressive improvement in game performance56. According to Villiger et al.57, several sensorimotor neuronal circuits can be increased when an individual performs a task with high motivation and engagement, and due to dopaminergic denervation in PD, any potential aspects that cause demotivation, such as negative feedback, should be avoided, which may reduce the adherence of players to the task58. Recent studies of functional brain connectivity show that learning in PD can benefit from a reward-based approach59.
In the secondary analyses, our results showed that in both groups the majority of the enjoyment scores remained in the “fun” and “great fun” levels on all the intervention days. Although there was no difference between the sequences, we can speculate that having fun while playing and performing a VR task enhanced the possibility of the individual becoming more committed to rehabilitation through individualized training, and also to becoming more involved by allowing themselves to experience different types of environments through sensors and receiving feedback, especially on their audio-visual senses60.
We can speculate that the music played in the background, and the colored spheres could be also motivational factors that contribute to improved performance and transform the therapy into a playful environment61. The same musical rhythm was offered to all participants in the present study. Playing music in the background may have contributed to the improvement in performance during the proposed task, as listening to music improves neuronal connectivity in specific regions of the brain of healthy participants, and musical activities promote neural plasticity and induce gray and white matter alterations in various regions of the brain, especially in areas of the frontal and temporal lobes62-64.
According to the meta-analysis by Triegaardt et al.21, the exact mechanisms by which VR improves the motor performance of individuals with PD are not yet fully understood. Nevertheless, studies have shown that patients can learn motor skills in virtual environments and that these are easily implemented in real life65.
Combined Intervention
Considering the use of VR and tDCS, our results demonstrated that the individuals in the active tDCS presented significantly greater improvement than the sham tDCS. This indicates that performing the task while receiving tDCS therapy could help patients progressively improve during the game practice. During the timing coincident task used, 8 minutes, the patients improved from one block to the next, despite this being their first contact with the game.
There are still many uncertainties surrounding the neurophysiological mechanism of tDCS66. Nevertheless, a meta-analysis by Chase et al.67, reveals growing confidence in this method, describing the impact on neural activity and behavior, including motor thresholds, prefrontal cortex-related cognition, and depression. According to this recent meta-analysis, available data from animal and human studies suggest that the parameters used in humans currently modulate neural activity through changes in electrical fields and neural oscillations, rather than triggering neuronal spikes. tDCS can increase ventral posterolateral thalamic nucleus activity and can influence basal ganglia function67. Furthermore, anodic tDCS over the motor cortex alters the resting membrane potentials of underlying neurons, leading to increased cortical excitability, with immediate and long-term effects that have been proposed to help improve motor skills68.
As tDCS has a modulating role in neural activity and with the various studies in the field that have been growing exponentially69, a meta-analysis identified that tDCS is more effective when the goal of therapy is for the individual to learn a new task, rather than to improve performance in a previously learned task70.
People with PD face difficulties in consolidating new motor skills, and electrostimulation techniques can optimize neuronal circuits, and even increase compensatory mechanisms of cortical excitability, thus facilitating the acquisition of new motor skills71,72 Evidence suggests that the use of combination therapies can bring greater and longer-lasting benefits in motor functions than therapies performed in isolation in healthy people73. A systematic review carried out by Massetti et al.25 noted that overall, combined tDCS + VR therapies show positive effects in diverse populations (cerebral palsy, healthy people, and individuals who have had a stroke) and evidence regarding the frequency and duration of therapies is still uncertain as well as specific targeting for each pathology.
Techniques such as tDCS have shown some success when combined with VR therapies, as in the study by Ang et al.74 who used this approach with people affected by a cerebrovascular accident (CVA) to facilitate motor imagination, obtaining positive results. Currently, models and protocols for determining tDCS assemblies are not yet fully elucidated, so investigations of the functioning of brain activity during the performance of a cognitive or motor task in a VR task still need to be elaborated in more depth to better define the pattern of cortical excitation induced by tDCS75.
The application of tDCS and the contact of individuals with the proposed task was carried out on only one day. The neurophysiological effects of tDCS, such as promoting synaptic plasticity and inducing lasting changes in excitability in the central nervous system, could not be thoroughly evaluated in just one day of application, even though positive effects were found42. In summary, there are still many open questions about the effects of tDCS applications on brain oscillations and the relationships that these effects may have on human brain functioning. To our knowledge, the first test to promote improvement in the patient’s motor function with PD using the combination of tDCS + VR was conducted by Harris et al.76. Therefore, the use of combined tDCS + VR therapy is still very recent. This study will contribute to observing the behavior the motor performance of individuals with PD when submitted to this combined therapy and support further longer-term trials.
Improvement in upper and lower limbs
Individuals with PD deal with difficulty in the control of movements, such as reaching and grasping due to motor disorders in the upper limbs related to the disease, which leads to slow execution of tasks that require a complex pattern of movements77. On the other hand, people with PD face other symptoms of the lower limbs, such as postural instability, balance problems, and gait disorders, which trigger falls and injuries, leading to difficulty performing daily life activities3. In this protocol, the task proposed had a high demand for both limbs and the fact that both groups presented improved scores for the two types of demand can predict that this task is effective for symptoms related to PD in both upper and lower limbs. However, we observed that this was more evident in the practice with the lower limbs considering the absolute error (i.e. our results showed improvement in the variable error for both upper and lower limbs, but for the absolute error we only observed improvement in the lower limbs).
We can only speculate that the fact that in the upper limb task (performed first) the player needed to always be in a standing position and move in different directions, this postural demand could facilitate the subsequent lower limb practice and influence the participant’s performance. It is well known that due to the basal ganglia dysfunction in PD, dysregulation of the anticipatory and feed-forward precision mechanism affects motor performance78. The studies of Jansen et al.79 presented a positive influence on the upper limb task when PD individuals practiced previous lower limb activities. The authors proposed that this could be influenced by exercises such as cycling and can modify the connectivity and function of the interaction between basal ganglia and cortical motor areas, by facilitating the function of these structures, which results in more coordinated and efficient bimanual movements80. We propose that the opposite should also be considered.
Thus, practicing an upper limb task in a standing position could positively influence the performance of the task performed with the lower limbs. Considering this supposition, the order of practice could be considered a first limitation of our study, but also an indication that future studies should be performed comparing the order of practice (upper or lower limbs) and its influence on motor performance.
Limitations and Future Studies
There are limitations to this study. (1) The protocol was for only one day, and it is important to observe if this progressive improvement in performance remains in the long term. Because this is a one-day protocol, we can speculate that a long period of practice (more days practicing the same VR task) would be positive for learning how to use the feedback given by the game and could cause greater automation of movement, with a more evident improvement in performance, which is actually what happens with VR games; if an individual practice a certain task, performance tends to improve progressively38; (2) The analysis performed in the present study focused mainly on motor skills, but it would be interesting to psychologically analyze the participants to observe possible changes in mood and behavior after the game; (3) In our protocol, the music played during the game was pre-selected by the researcher. Sihvonen et al.61 in a systematic review noted that most studies do not use music selected by the patient, however, due to the strong emotional factors involved in music, perhaps allowing the patient to choose their music during therapy would bring more benefits, as the music chosen by the patient could have some effect; and (4) Our findings support that a VR task designed for individuals with neurological disorders can be beneficial to motor performance in people with PD, but we did not compare this with a conventional and commercial game. Future studies should compare games available commercially with VR tasks projected for people with disabilities.
More details on the efficacy, safety, feasibility, and adherence of VR rehabilitation should be obtained and examined through more randomized controlled trials, directly specifying the goals to be achieved with a given type of intervention, game, or VR activity. The current evidence indicates that training protocols with VR are similar to non-VR-based training for people with PD, it is up to the therapist to precisely analyze the advantages and disadvantages of this approach and prescribe the intervention accordingly. There is also a great need to identify the profile of the specific individuals with PD who would benefit from this practice54.
Chuang et al.81 suggested in a recent meta-analysis that future studies should elaborate specific VR tasks for people with PD since some types of technology available commercially can be too complex for this population. The present study used a VR game designed especially for people with neurological diseases, the MoveHero game, which has been used in other studies, with different populations, and showed improvement in motor performance38,82.
Further studies should be carried out to investigate whether the effects of tDCS remain in subjects in the long term. The current study served as the basis for this future hypothesis, that the performance of subjects would continue to improve if they were exposed again to the combined application of tDCS and VR.
CONCLUSION
The active tDCS group performed better during the proposed task when compared to the sham tDCS, but both groups showed improved performance during the proposed task, both for accuracy (AE) and precision (VE). VR seems to be the future of rehabilitation for people with PD and its association with tDCS appears to be beneficial even after only one application. Studies with larger samples and with a prolonged period of treatment should be performed to establish whether these effects are maintained in the long term.
