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

Leena Subramanian, Monica Busse Morris, Meadhbh Brosnan, Duncan L Turner, Huw R Morris, David E J Linden, Leena Subramanian, Monica Busse Morris, Meadhbh Brosnan, Duncan L Turner, Huw R Morris, David E J Linden

Abstract

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.

Keywords: Parkinson’s disease; WiiFit; motor training; neurofeedback; real-time functional magnetic resonance imaging.

Figures

Figure 1
Figure 1
The CONSORT diagram shows the flow of patients through each stage of the randomized, controlled trial.
Figure 2
Figure 2
Flowchart of the study design with details of the interventions.
Figure 3
Figure 3
(A) “Off- medication” PRE- and POST-intervention mean scores of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor subscale (MS) for both groups with higher scores indicating greater impairment; (B) “On-medication” mean scores of the MDS-UPDRS MS for the three assessment sessions for both groups with higher scores indicating greater impairment; (C) “On-medication” mean scores of the non-motor experience of daily living (NM-DL) sub scale of the MDS-UPDRS for the three assessment sessions for both groups; (D) “On-medication” mean scores of the motor-experience of daily living sub scale of the MDS-UPDRS for the three assessment sessions for both groups. * indicates significant difference.
Figure 4
Figure 4
(A) Mean beta values from the neurofeedback (NF) scans for the three different sessions in weeks 2, 6 and 12 of the NF intervention. Bars are standard errors; (B) Areas of significant activation across all NF sessions (whole brain based analysis). (C) Sagittal view of the brain showing a probabilistic map of the overlap across regions of interest (ROI’s) supplementary motor area (SMA) used for NF training across patients. PM, probabilistic map.

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