Modulating functional connectivity after stroke with neurofeedback: Effect on motor deficits in a controlled cross-over study

Abstract

Synchronization of neural activity as measured with functional connectivity (FC) is increasingly used to study the neural basis of brain disease and to develop new treatment targets. However, solid evidence for a causal role of FC in disease and therapy is lacking. Here, we manipulated FC of the ipsilesional primary motor cortex in ten chronic human stroke patients through brain-computer interface technology with visual neurofeedback. We conducted a double-blind controlled crossover study to test whether manipulation of FC through neurofeedback had a behavioral effect on motor performance. Patients succeeded in increasing FC in the motor cortex. This led to improvement in motor function that was significantly greater than during neurofeedback training of a control brain area and proportional to the degree of FC enhancement. This result provides evidence that FC has a causal role in neurological function and that it can be effectively targeted with therapy.

Keywords: Brain-computer interface; EEG; FC, Functional Connectivity; FMA, Fugl-Meyer Assessment; Functional connectivity; MNI, Montreal Neurological Institude; Motor cortex; SnPM, Statistical non-parametric mapping; Stroke.

Fig. 1

Clinical effect of FC neurofeedback in the ten patients. a) Boxplot of Fugl-Meyer assessment score improvements obtained during the month of neurofeedback training, as well as at one month follow-up. * indicates a significant difference between treatment conditions (p < .05, Student's t-test). b) Mean (± standard error) evolution of the FMA score for both treatment orders. Continuous lines indicate training periods and dashed lines periods without training. † indicates one missing value.

Fig. 2

Neural effect of the FC neurofeedback in the ten patients. Regions showing a significant modulation (red and blue colors) of the weighted node degree in the alpha-band (a) and at 10 Hz (b) during the neurofeedback sessions targeting the ipsilesional motor cortex (marked in grey). Regions showing a significant modulation (red and blue colors) of the weighted node degree in the alpha-band (c) and at 8 Hz (d) during the neurofeedback sessions targeting the contralesional prefrontal cortex (marked in grey). e) Regions showing a correlation between enhancements in alpha-band weighted node degree at the ipsilesional motor cortex (grey area) and change in the upper extremity FMA score. f) Enhancements of alpha-band weighted node degree at the targeted ipsilesional motor cortex were associated with a proportional increase in the upper extremity FMA score.

Fig. 3

FC evolution during neurofeedback sessions. Each line represents the evolution in one patient of its FC during neurofeedback sessions, averaged over the eight sessions. FC values are the alpha-band weighted node degree calculated over ten minutes of neurofeedback (z-normalized). The color scale indicates the individual motor improvement as measured with the FMA score.

Fig. 4

FMA score improvement in patients with a right-sided (grey) and a left-sided (black) lesion after the neurofeedback sessions targeting the ipsilesional motor cortex (a) and at one-month follow-up (b). * Indicates a significant difference in long-term FMA improvement between patients with left-sided and right-sided lesions (p < .05, Wilcoxon rank-sum test).