Functional Magnetic Resonance Imaging Neurofeedback-guided Motor Imagery Training and Motor Training for Parkinson’s Disease: Randomized Trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behavior and clinical symptoms. The objective was to determine the effect of NF and motor training (MOT) alone on motor and non-motor functions in Parkinson’s Disease (PD) in a 10-week small Phase I randomized controlled trial. Methods: Thirty patients with Parkinson’s disease (PD; Hoehn and Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with MOT. Group 2 (MOT: 15 patients) received MOT alone. The primary outcome measure was the Movement Disorder Society—Unified PD Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention “off-medication”. The secondary outcome measures were the “on-medication” MDS-UPDRS, the PD Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area (SMA) by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the “off-medication” state (95% confidence interval: −2.5 to −6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to −6.8). The improvement in the intervention group meets the minimal clinically important difference which is also on par with other non-invasive therapies such as repetitive Transcranial Magnetic Stimulation (rTMS). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with MOT is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions.

[1]  J. Jankovic,et al.  Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Scale presentation and clinimetric testing results , 2008, Movement disorders : official journal of the Movement Disorder Society.

[2]  Dagmar Verbaan,et al.  The MoCA: Well-suited screen for cognitive impairment in Parkinson disease , 2011, Neurology.

[3]  Niels Birbaumer,et al.  Reorganization of functional and effective connectivity during real-time fMRI-BCI modulation of prosody processing , 2011, Brain and Language.

[4]  C. Tanner,et al.  Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030 , 2007, Neurology.

[5]  Kevin A. Johnson,et al.  Intermittent “Real‐time” fMRI Feedback Is Superior to Continuous Presentation for a Motor Imagery Task: A Pilot Study , 2012, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[6]  Hylton B. Menz,et al.  Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease , 2011, Parkinson's disease.

[7]  Christopher Bishop,et al.  Critical involvement of the motor cortex in the pathophysiology and treatment of Parkinson's disease , 2013, Neuroscience & Biobehavioral Reviews.

[8]  W. Poewe,et al.  The clinical spectrum of levodopa-induced motor complications , 2010, Journal of Neurology.

[9]  A. Gordon,et al.  Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements , 1998, Experimental Brain Research.

[10]  Carolyn Copper,et al.  Does mental practice enhance performance , 1994 .

[11]  Rainer Goebel,et al.  Neurofeedback: A promising tool for the self-regulation of emotion networks , 2010, NeuroImage.

[12]  C. J. McGrath,et al.  Effect of exchange rate return on volatility spill-over across trading regions , 2012 .

[13]  R. Simpson,et al.  Risks of common complications in deep brain stimulation surgery: management and avoidance. , 2014, Journal of neurosurgery.

[14]  Li Yao,et al.  Functional connectivity alteration after real-time fMRI motor imagery training through self-regulation of activities of the right premotor cortex , 2015, BMC Neuroscience.

[15]  Nikolaus Weiskopf,et al.  Real-time fMRI and its application to neurofeedback , 2012, NeuroImage.

[16]  Geraint Rees,et al.  Connectivity Changes Underlying Neurofeedback Training of Visual Cortex Activity , 2014, PloS one.

[17]  Erwan Bezard,et al.  Presymptomatic compensation in Parkinson's disease is not dopamine-mediated , 2003, Trends in Neurosciences.

[18]  Li Yao,et al.  Modulation of functional network with real-time fMRI feedback training of right premotor cortex activity , 2014, Neuropsychologia.

[19]  J. Rothwell,et al.  Endogenous control of waking brain rhythms induces neuroplasticity in humans , 2010, The European journal of neuroscience.

[20]  Maarten De Vos,et al.  Real-time EEG feedback during simultaneous EEG–fMRI identifies the cortical signature of motor imagery , 2015, NeuroImage.

[21]  M. Pinter,et al.  Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson’s disease: a double blind, placebo controlled, randomised, multicentre study , 1999, Journal of neurology, neurosurgery, and psychiatry.

[22]  C. Kennard,et al.  Functional role of the supplementary and pre-supplementary motor areas , 2008, Nature Reviews Neuroscience.

[23]  R. DeCharms Applications of real-time fMRI , 2008, Nature Reviews Neuroscience.

[24]  R. Goebel,et al.  Real-Time Functional Magnetic Resonance Imaging Neurofeedback for Treatment of Parkinson's Disease , 2011, The Journal of Neuroscience.

[25]  M. Walker,et al.  Clinical effectiveness and cost-effectiveness of physiotherapy and occupational therapy versus no therapy in mild to moderate Parkinson's disease: a large pragmatic randomised controlled trial (PD REHAB). , 2016, Health technology assessment.

[26]  D. Linden,et al.  Neural networks and neurofeedback in Parkinson's Disease , 2014 .

[27]  M. Breteler,et al.  Epidemiology of Parkinson's disease , 2006, The Lancet Neurology.

[28]  Mark Chiew,et al.  Investigation of fMRI neurofeedback of differential primary motor cortex activity using kinesthetic motor imagery , 2012, NeuroImage.

[29]  D. Calne,et al.  Pharmacological Treatment of Parkinson’s Disease , 1986 .

[30]  E. Katunina,et al.  [Epidemiology of Parkinson's disease]. , 2013, Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.

[31]  M. Bove,et al.  Motor cortical plasticity induced by motor learning through mental practice , 2015, Front. Behav. Neurosci..

[32]  Ruth Dickstein,et al.  Integration of Motor Imagery and Physical Practice in Group Treatment Applied to Subjects With Parkinson’s Disease , 2007, Neurorehabilitation and neural repair.

[33]  N. Birbaumer,et al.  Learned regulation of brain metabolism , 2013, Trends in Cognitive Sciences.

[34]  Gary H. Glover,et al.  Learned regulation of spatially localized brain activation using real-time fMRI , 2004, NeuroImage.

[35]  W. Weiner,et al.  The clinically important difference on the unified Parkinson's disease rating scale. , 2010, Archives of neurology.

[36]  L. Jason,et al.  The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome. , 2011, Rehabilitation psychology.

[37]  C. Clarke,et al.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[38]  Anette Schrag,et al.  Minimal clinically important change on the unified Parkinson's disease rating scale , 2006, Movement disorders : official journal of the Movement Disorder Society.

[39]  Bettina Sorger,et al.  Real-Time Self-Regulation of Emotion Networks in Patients with Depression , 2012, PloS one.

[40]  Linda Tapsell,et al.  Relative validity of 3 accelerometer models for estimating energy expenditure during light activity. , 2014, Journal of physical activity & health.

[41]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[42]  A. Lang,et al.  Behavioral effects of levodopa , 2015, Movement disorders : official journal of the Movement Disorder Society.

[43]  Thomas Eickermann,et al.  A new approach to measure single‐event related brain activity using real‐time fMRI: Feasibility of sensory, motor, and higher cognitive tasks , 2001, Human brain mapping.

[44]  Jong-Hwan Lee,et al.  Neurofeedback fMRI‐mediated learning and consolidation of regional brain activation during motor imagery , 2008, Int. J. Imaging Syst. Technol..

[45]  Dandan Huang,et al.  Effect of real-time cortical feedback in motor imagery-based mental practice training. , 2014, NeuroRehabilitation.

[46]  Jonathan W. Peirce,et al.  PsychoPy—Psychophysics software in Python , 2007, Journal of Neuroscience Methods.

[47]  A. Lang,et al.  Pharmacological treatment of Parkinson disease: a review. , 2014, JAMA.

[48]  Marios Politis,et al.  Neuroimaging in Parkinson disease: from research setting to clinical practice , 2014, Nature Reviews Neurology.

[49]  J. Pillai Functional Connectivity. , 2017, Neuroimaging clinics of North America.

[50]  M. Onofrj,et al.  Improvement of motor function in early Parkinson disease by safinamide , 2004, Neurology.

[51]  Nathan Intrator,et al.  Limbic Activity Modulation Guided by Functional Magnetic Resonance Imaging–Inspired Electroencephalography Improves Implicit Emotion Regulation , 2016, Biological Psychiatry.

[52]  M Hallett,et al.  Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences. , 1997, Brain : a journal of neurology.

[53]  M. Mak,et al.  Technology-Assisted Balance and Gait Training Reduces Falls in Patients With Parkinson’s Disease , 2015, Neurorehabilitation and neural repair.

[54]  U. Dalgas,et al.  Parkinson's disease and intensive exercise therapy – a systematic review and meta-analysis of randomized controlled trials , 2015, Journal of the Neurological Sciences.

[55]  L. Bour,et al.  Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial , 2013, The Lancet Neurology.

[56]  Á. Pascual-Leone,et al.  Non-invasive brain stimulation for Parkinson’s disease: a systematic review and meta-analysis of the literature , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[57]  A. Ashburn,et al.  The PIT: SToPP Trial—A Feasibility Randomised Controlled Trial of Home-Based Physiotherapy for People with Parkinson's Disease Using Video-Based Measures to Preserve Assessor Blinding , 2011, Parkinson's disease.

[58]  Seung-Schik Yoo,et al.  Functional MRI for neurofeedback: feasibility studyon a hand motor task , 2002, Neuroreport.

[59]  F. Jolesz,et al.  Brain–machine interface via real-time fMRI: Preliminary study on thought-controlled robotic arm , 2009, Neuroscience Letters.

[60]  Lynn Rochester,et al.  The role of exergaming in Parkinson’s disease rehabilitation: a systematic review of the evidence , 2014, Journal of NeuroEngineering and Rehabilitation.

[61]  Carol M. Ashton,et al.  On the clinically important difference , 1992, ACP Journal Club.

[62]  Laehyun Kim,et al.  Which motor cortical region best predicts imagined movement? , 2015, NeuroImage.

[63]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[64]  J. Jefferson,et al.  Psychiatric complications of deep brain stimulation for Parkinson's disease. , 2004, The Journal of clinical psychiatry.

[65]  Sven Haller,et al.  Real-time fMRI neurofeedback: Progress and challenges , 2013, NeuroImage.