Does Fractional Anisotropy Predict Motor Imagery Neurofeedback Performance in Healthy Older Adults?

Motor imagery neurofeedback training has been proposed as a potential add-on therapy for motor impairment after stroke, but not everyone benefits from it. Previous work has used white matter integrity to predict motor imagery neurofeedback aptitude in healthy young adults. We set out to test this approach with motor imagery neurofeedback that is closer to that used for stroke rehabilitation and in a sample whose age is closer to that of typical stroke patients. Using shrinkage linear discriminant analysis with fractional anisotropy values in 48 white matter regions as predictors, we predicted whether each participant in a sample of 21 healthy older adults (48–77 years old) was a good or a bad performer with 84.8% accuracy. However, the regions used for prediction in our sample differed from those identified previously, and previously suggested regions did not yield significant prediction in our sample. Including demographic and cognitive variables which may correlate with motor imagery neurofeedback performance and white matter structure as candidate predictors revealed an association with age but also led to loss of statistical significance and somewhat poorer prediction accuracy (69.6%). Our results suggest cast doubt on the feasibility of predicting the benefit of motor imagery neurofeedback from fractional anisotropy. At the very least, such predictions should be based on data collected using the same paradigm and with subjects whose characteristics match those of the target case as closely as possible

Inter-individual variability in current direction for common tDCS montages

The direction of applied electric current relative to the cortical surface is a key determinant of transcranial direct current stimulation (tDCS) effects. Inter-individual differences in anatomy affect the consistency of current direction at a cortical target, likely leading to inter-individual variability in current direction. However, the degree of this variability remains undetermined. Using current flow modelling (CFM), we quantified the inter-individual variability in tDCS current direction at a cortical target (left primary motor cortex, M1). Three montages targeting M1 using circular electrodes were compared: PA-tDCS directed current perpendicular to the central sulcus in a posterior-anterior direction relative to M1, ML-tDCS directed current parallel to the central sulcus in a medio-lateral direction, and conventional-tDCS applied electrodes over M1 and the contralateral forehead. In 50 healthy brain scans from the Human Connectome Project, we extracted current direction and intensity from the gray matter surface in the sulcal bank (M1BANK) and gyral crown (M1CROWN), and neighbouring primary somatosensory cortex (S1BANK and S1CROWN). Results confirmed substantial inter-individual variability in current direction (50%-150%) across all montages. Radial inward current produced by PA-tDCS was predominantly located in M1BANK, whereas for conventional-tDCS it was clustered in M1CROWN. The predominantly radial inward current in functionally distinct subregions of M1 raises the testable hypothesis that PA-tDCS and conventional-tDCS modulate cortical excitability through different mechanisms. We show that electrode locations can be used to closely approximate current direction in M1 and precentral gyrus, providing a landmark-based method for tDCS application to address the hypothesis without the need for MRI. By contrast, ML-tDCS current was more tangentially oriented, which is associated with little somatic polarization. Substantial inter-individual variability in current direction likely contributes to variable neuromodulation effects reported for these protocols, emphasising the need for individualised electrode montages, including the control of current direction

Investigating Different Levels of Bimanual Interaction With a Novel Motor Learning Task: A Behavioural and Transcranial Alternating Current Stimulation Study

Many tasks require the skilled interaction of both hands, such as eating with knife and fork or keyboard typing. However, our understanding of the behavioural and neurophysiological mechanisms underpinning bimanual motor learning is still sparse. Here, we aimed to address this by first characterising learning-related changes of different levels of bimanual interaction and second investigating how beta tACS modulates these learning-related changes. To explore early bimanual motor learning, we designed a novel bimanual motor learning task. In the task, a force grip device held in each hand (controlling x- and y-axis separately) was used to move a cursor along a path of streets at different angles (0°, 22.5°, 45°, 67.5°, and 90°). Each street corresponded to specific force ratios between hands, which resulted in different levels of hand interaction, i.e., unimanual (Uni, i.e., 0°, 90°), bimanual with equal force (Bieq, 45°), and bimanual with unequal force (Biuneq 22.5°, 67.5°). In experiment 1, 40 healthy participants performed the task for 45 min with a minimum of 100 trials. We found that the novel task induced improvements in movement time and error, with no trade-off between movement time and error, and with distinct patterns for the three levels of bimanual interaction. In experiment 2, we performed a between-subjects, double-blind study in 54 healthy participants to explore the effect of phase synchrony between both sensorimotor cortices using tACS at the individual’s beta peak frequency. The individual’s beta peak frequency was quantified using electroencephalography. 20 min of 2 mA peak-to-peak amplitude tACS was applied during task performance (40 min). Participants either received in-phase (0° phase shift), out-of-phase (90° phase shift), or sham (3 s of stimulation) tACS. We replicated the behavioural results of experiment 1, however, beta tACS did not modulate motor learning. Overall, the novel bimanual motor task allows to characterise bimanual motor learning with different levels of bimanual interaction. This should pave the way for future neuroimaging studies to further investigate the underlying mechanism of bimanual motor learning

Investigating Priming Effects of Physical Practice on Motor Imagery-Induced Event-Related Desynchronization

For motor imagery (MI) to be effective, an internal representation of the to-be-imagined movement may be required. A representation can be achieved through prior motor execution (ME), but the neural correlates of MI that are primed by ME practice are currently unknown. In this study, young healthy adults performed MI practice of a unimanual visuo-motor task (Group MI, n = 19) or ME practice combined with subsequent MI practice (Group ME&MI, n = 18) while electroencephalography (EEG) was recorded. Data analysis focused on the MI-induced event-related desynchronization (ERD). Specifically, changes in the ERD and movement times (MT) between a short familiarization block of ME (Block pre-ME), conducted before the MI or the ME combined with MI practice phase, and a short block of ME conducted after the practice phase (Block post-ME) were analyzed. Neither priming effects of ME practice on MI-induced ERD were found nor performance-enhancing effects of MI practice in general. We found enhancements of the ERD and MT in Block post-ME compared to Block pre-ME, but only for Group ME&MI. A comparison of ME performance measures before and after the MI phase indicated however that these changes could not be attributed to the combination of ME and MI practice. The mixed results of this study may be a consequence of the considerable intra- and inter-individual differences in the ERD, introduced by specifics of the experimental setup, in particular the individual and variable task duration, and suggest that task and experimental setup can affect the interplay of ME and MI

The impact of brain lesions on tDCS-induced electric fields

Transcranial direct current stimulation (tDCS) can enhance motor and language rehabilitation after stroke. Though brain lesions distort tDCS-induced electric field (E-field), systematic accounts remain limited. Using electric field modelling, we investigated the effect of 630 synthetic lesions on E-field magnitude in the region of interest (ROI). Models were conducted for two tDCS montages targeting either primary motor cortex (M1) or Broca's area (BA44). Absolute E-field magnitude in the ROI differed by up to 42% compared to the non-lesioned brain depending on lesion size, lesion-ROI distance, and lesion conductivity value. Lesion location determined the sign of this difference: lesions in-line with the predominant direction of current increased E-field magnitude in the ROI, whereas lesions located in the opposite direction decreased E-field magnitude. We further explored how individualised tDCS can control lesion-induced effects on E-field. Lesions affected the individualised electrode configuration needed to maximise E-field magnitude in the ROI, but this effect was negligible when prioritising the maximisation of radial inward current. Lesions distorting tDCS-induced E-field, is likely to exacerbate inter-individual variability in E-field magnitude. Individualising electrode configuration and stimulator output can minimise lesion-induced variability but requires improved estimates of lesion conductivity. Individualised tDCS is critical to overcome E-field variability in lesioned brains

Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood-flow independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings, and offers substantial promise to investigate physiological mechanisms, but behaviourally-relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven Hidden Markov Model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both p < 0.001). Hidden Markov Model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared to controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes

The GLM-spectrum:A multilevel framework for spectrum analysis with covariate and confound modelling

The frequency spectrum is a central method for representing the dynamics within electrophysiological data. Some widely used spectrum estimators make use of averaging across time segments to reduce noise in the final spectrum. The core of this approach has not changed substantially since the 1960s, though many advances in the field of regression modelling and statistics have been made during this time. Here, we propose a new approach, the General Linear Model (GLM) Spectrum, which reframes time averaged spectral estimation as multiple regression. This brings several benefits, including the ability to do confound modelling, hierarchical modelling, and significance testing via non-parametric statistics. We apply the approach to a dataset of EEG recordings of participants who alternate between eyes-open and eyes-closed resting state. The GLM-Spectrum can model both conditions, quantify their differences, and perform denoising through confound regression in a single step. This application is scaled up from a single channel to a whole head recording and, finally, applied to quantify age differences across a large group-level dataset. We show that the GLM-Spectrum lends itself to rigorous modelling of within- and between-subject contrasts as well as their interactions, and that the use of model-projected spectra provides an intuitive visualisation. The GLM-Spectrum is a flexible framework for robust multilevel analysis of power spectra, with adaptive covariate and confound modelling

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand

Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements

Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future

Bimanual motor task comprising 5 learning and 3 transfer conditions (behavioural data)

Full description of dataset and download is available at: https://data.mrc.ox.ac.uk/bimanual-motor-tas