Virtual reality-based treatment for regaining upper extremity function induces cortex grey matter changes in persons with acquired brain injury

Jiří Keller, Ivana Štětkářová, Vince Macri, Simone Kühn, Jakub Pětioký, Stefano Gualeni, С Douglas Simmons, Sajay Arthanat, Paul Zilber, Jiří Keller, Ivana Štětkářová, Vince Macri, Simone Kühn, Jakub Pětioký, Stefano Gualeni, С Douglas Simmons, Sajay Arthanat, Paul Zilber

Abstract

Background: Individuals with acquired brain injuries (ABI) are in need of neurorehabilitation and neurorepair. Virtual anatomical interactivity (VAI) presents a digital game-like format in which ABI survivors with upper limb paresis use an unaffected limb to control a standard input device and a commonplace computer mouse to control virtual limb movements and tasks in a virtual world.

Methods: In a prospective cohort study, 35 ambulatory survivors of ABI (25/71% stroke, 10/29% traumatic brain injury) were enrolled. The subjects were divided into three groups: group A received VAI therapy only, group B received VAI and physical/occupational therapy (P/OT), and group C received P/OT only. Motor skills were evaluated by muscle strength (hand key pinch strength, grasp, and three-jaw chuck pinch) and active range of motion (AROM) of the shoulder, elbow, and wrist. Changes were analyzed by ANOVA, ANCOVA, and one-tailed Pearson correlation analysis. MRI data was acquired for group A, and volumetric changes in grey matter were analyzed using voxel-based morphometry (VBM) and correlated with quantified motor skills.

Results: AROM of the shoulder, elbow, and wrist improved in all three groups. VBM revealed grey matter increases in five brain areas: the tail of the hippocampus, the left caudate, the rostral cingulate zone, the depth of the central sulcus, and the visual cortex. A positive correlation between the grey matter volumes in three cortical regions (motor and premotor and supplementary motor areas) and motor test results (power and AROM) was detected.

Conclusions: Our findings suggest that the VAI rehabilitation program significantly improved motor function and skills in the affected upper extremities of subjects with acquired brain injuries. Significant increases in grey matter volume in the motor and premotor regions of affected hemisphere and correlations of motor skills and volume in nonaffected brain regions were present, suggesting marked changes in structural brain plasticity.

Trial registration: The trial "Limitations of motor brain activity - use of virtual reality for simulation of therapeutic interventions" has been registered under reference number ISRCTN11757651 .

Keywords: Acquired brain injury (ABI); Brain plasticity; Magnetic resonance imaging (MRI); Rehabilitation; Stroke; Therapeutic games; Traumatic brain injury (TBI); Video-observation-feedback therapy; Virtual anatomical interactivity (VAI); Virtual world.

Conflict of interest statement

In the present study, 3DPreMotorSkill Technologies, LLC contributed financial support to nearly all of the study components, including stipends to survivor-participants in group A and charges for MRI services. 3DPreMotorSkill Technologies, LLC is a research and development (R&D) company. It has never sold anything and it has never earned revenue from any source other than R&D grants. Significant contributions of financial support was given by the military endowment fund REGIBASE and the Kladruby Rehabilitation Center to Jakub Pětioký. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Examples of VAI games: multi-finger actions to pick up a spoon and drop it into a cup, tapping actions using the index and middle fingers on a remote control, removing a light bulb and reinserting it into another fixture designated by a letter of the alphabet, choosing letters of the alphabet to form words and phrases. All actions are performed by clicking and draging mouse on the appropriate body part
Fig. 2
Fig. 2
Motor achievements: a grip strengths before and after intervention. In parts bd, estimated marginal means of gains are presented for b grip strengths, c shoulder abduction, and d shoulder flexion. In graphs b, c, and d the covariates appearing in the model are evaluated at the following values: therapy hours = 152.2466
Fig. 3
Fig. 3
Results of voxel-based morphometry, nonstationary smoothness corrected p < 0.005, cluster size > 200. Neurological convention (left side of the brain is on the left side of the picture). Grey matter (GM) volume increased in the left postcentral gyrus (a), tail of the left hippocampus (b), left visual cortex and left prefrontal areas 8 and 32 (c), and left caudate (d)

References

    1. Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the global burden of Disease study 2015. Lancet Neurol. 2017;16(11):877–897. doi: 10.1016/S1474-4422(17)30299-5.
    1. Writing Group Members. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et al. Heart Disease and Stroke Statistics—2012 Update: A Report From the American Heart Association. Circulation. 2012;125(1):e2–e220. doi: 10.1161/CIR.0b013e318245fac5.
    1. Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global burden of diseases, injuries, risk factors study 2010 (GBD 2010); GBD stroke experts group. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the global burden of Disease study 2010. Lancet Glob Health. 2013;1(5):e259–e281. doi: 10.1016/S2214-109X(13)70089-5.
    1. Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79(17):1781–1787. doi: 10.1212/WNL.0b013e318270401d.
    1. Kwakkel G, Kollen BJ, van der Grond J, Prevo AJH. Probability of regaining dexterity in the flaccid upper limb: impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34(9):2181–2186. doi: 10.1161/.
    1. Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8(8):741–754. doi: 10.1016/S1474-4422(09)70150-4.
    1. Morris JH, van Wijck F, Joice S, Donaghy M. Predicting health related quality of life 6 months after stroke: the role of anxiety and upper limb dysfunction. Disabil Rehabil. 2013;35(4):291–299. doi: 10.3109/09638288.2012.691942.
    1. Coleman ER, Moudgal R, Lang K, Hyacinth HI, Awosika OO, Kissela BM, et al. Early rehabilitation after stroke: a narrative review. Curr Atheroscler Rep. 2017;19(12):59. doi: 10.1007/s11883-017-0686-6.
    1. Nijboer T, van de Port I, Schepers V, Post M, Visser-Meily A. Predicting functional outcome after stroke: the influence of neglect on basic activities in daily living. Front Hum Neurosci. 2013;7:182. doi: 10.3389/fnhum.2013.00182.
    1. Rasova K, Prochazkova M, Tintera J, Ibrahim I, Zimova D, Stetkarova I. Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study. Int J Rehabil Res Int Z Rehabil Rev Int Rech Readaptation. 2015;38(1):49–54.
    1. Proffitt R, Lange B. Feasibility of a customized, in-home, game-based stroke exercise program using the Microsoft Kinect® sensor. Int J Telerehabilitation. 2015;7(2):23–34. doi: 10.5195/IJT.2015.6177.
    1. Wille D, Eng K, Holper L, Chevrier E, Hauser Y, Kiper D, et al. Virtual reality-based paediatric interactive therapy system (PITS) for improvement of arm and hand function in children with motor impairment--a pilot study. Dev Neurorehabilitation. 2009;12(1):44–52. doi: 10.1080/17518420902773117.
    1. Kühn S, Gleich T, Lorenz RC, Lindenberger U, Gallinat J. Playing super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game. Mol Psychiatry. 2014;19(2):265–271. doi: 10.1038/mp.2013.120.
    1. Kühn S, Gallinat J. Amount of lifetime video gaming is positively associated with entorhinal, hippocampal and occipital volume. Mol Psychiatry. 2014;19(7):842–847. doi: 10.1038/mp.2013.100.
    1. Gualeni S. Virtual worlds as philosophical tools: how to philosophize with a digital hammer. New York: Palgrave Macmillan; 2015.
    1. Goršič M, Cikajlo I, Novak D. Competitive and cooperative arm rehabilitation games played by a patient and unimpaired person: effects on motivation and exercise intensity. J NeuroEngineering Rehabil. 2017;14, 23(1) [cited 2019 Mar 4] Available from: .
    1. Shin J-H, Kim M-Y, Lee J-Y, Jeon Y-J, Kim S, Lee S, et al. Effects of virtual reality-based rehabilitation on distal upper extremity function and health-related quality of life: a single-blinded, randomized controlled trial. J Neuroengineering Rehabil. 2016;13:17. doi: 10.1186/s12984-016-0125-x.
    1. Perez-Marcos D, Chevalley O, Schmidlin T, Garipelli G, Serino A, Vuadens P, et al. Increasing upper limb training intensity in chronic stroke using embodied virtual reality: a pilot study. J Neuroengineering Rehabil. 2017;14(1):119. doi: 10.1186/s12984-017-0328-9.
    1. Simmons CD, Arthanat S, Macri VJ. Pilot study: computer-based virtual anatomical interactivity for rehabilitation of individuals with chronic acquired brain injury. J Rehabil Res Dev. 2014;51(3):377–390. doi: 10.1682/JRRD.2013.05.0103.
    1. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res. 1981;4(4):483–492. doi: 10.1097/00004356-198112000-00001.
    1. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2):206–207. doi: 10.1093/ptj/67.2.206.
    1. Pandyan AD, Price CIM, Barnes MP, Johnson GR. A biomechanical investigation into the validity of the modified Ashworth scale as a measure of elbow spasticity. Clin Rehabil. 2003;17(3):290–293. doi: 10.1191/0269215503cr610oa.
    1. Kwon J-S, Park M-J, Yoon I-J, Park S-H. Effects of virtual reality on upper extremity function and activities of daily living performance in acute stroke: a double-blind randomized clinical trial. NeuroRehabilitation. 2012;31(4):379–385. doi: 10.3233/NRE-2012-00807.
    1. Levin MF, Weiss PL, Keshner EA. Emergence of virtual reality as a tool for upper limb rehabilitation: incorporation of motor control and motor learning principles. Phys Ther. 2015;95(3):415–425. doi: 10.2522/ptj.20130579.
    1. Orihuela-Espina F, Fernández del Castillo I, Palafox L, Pasaye E, Sánchez-Villavicencio I, Leder R, et al. Neural reorganization accompanying upper limb motor rehabilitation from stroke with virtual reality-based gesture therapy. Top Stroke Rehabil. 2013;20(3):197–209. doi: 10.1310/tsr2003-197.
    1. Sampson M, Shau Y-W, King MJ. Bilateral upper limb trainer with virtual reality for post-stroke rehabilitation: case series report. Disabil Rehabil Assist Technol. 2012;7(1):55–62. doi: 10.3109/17483107.2011.562959.
    1. Karamians R, Proffitt R, Kline D, Gauthier LV. Effectiveness of virtual reality- and gaming-based interventions for upper extremity rehabilitation Post-stroke: a meta-analysis. Arch Phys Med Rehabil. 2019. 10.1016/j.apmr.2019.10.195.
    1. Filevich E, Lisofsky N, Becker M, Butler O, Lochstet M, Martensson J, Wenger E, Lindenberger U, Kühn S. Day2day: investigating daily variability of magnetic resonance imaging measures over half a year. BMC Neurosci. 2017;18(1):65. doi: 10.1186/s12868-017-0383-y.
    1. Zatorre RJ, Fields RD, Johansen-Berg H. Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci. 2012;15(4):528–536. doi: 10.1038/nn.3045.
    1. Lacourse MG, Turner JA, Randolph-Orr E, Schandler SL, Cohen MJ. Cerebral and cerebellar sensorimotor plasticity following motor imagery-based mental practice of a sequential movement. J Rehabil Res Dev. 2004;41(4):505–524. doi: 10.1682/JRRD.2004.04.0505.
    1. Dickstein R, Levy S, Shefi S, Holtzman S, Peleg S, Vatine J-J. Motor imagery group practice for gait rehabilitation in individuals with post-stroke hemiparesis: a pilot study. NeuroRehabilitation. 2014;34(2):267–276. doi: 10.3233/NRE-131035.
    1. Vromen A, Verbunt JA, Rasquin S, Wade DT. Motor imagery in patients with a right hemisphere stroke and unilateral neglect. Brain Inj. 2011;25(4):387–393. doi: 10.3109/02699052.2011.558041.
    1. Müller P, Rehfeld K, Schmicker M, Hökelmann A, Dordevic M, Lessmann V, et al. Evolution of neuroplasticity in response to physical activity in old age: the case for dancing. Front Aging Neurosci. 2017;9:56.
    1. Tanaka S, Ikeda H, Kasahara K, Kato R, Tsubomi H, Sugawara SK, et al. Larger right posterior parietal volume in action video game experts: a behavioral and voxel-based morphometry (VBM) study. PLoS One. 2013;8(6):e66998. doi: 10.1371/journal.pone.0066998.
    1. You SH, Jang SH, Kim Y-H, Kwon Y-H, Barrow I, Hallett M. Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy. Dev Med Child Neurol. 2005;47(9):628–635. doi: 10.1111/j.1469-8749.2005.tb01216.x.

Source: PubMed

3
Suscribir