Single session cross-frequency bifocal tACS modulates visual motion network activity in young healthy population and stroke patients.

BACKGROUND: Phase synchronization over long distances underlies inter-areal communication and importantly, modulates the flow of information processing to adjust to cognitive demands. OBJECTIVE: This study investigates the impact of single-session, cross-frequency (Alpha-Gamma) bifocal transcranial alternating current stimulation (cf-tACS) to the cortical visual motion network on inter-areal coupling between the primary visual cortex (V1) and the medio-temporal area (MT) and on motion direction discrimination. METHODS: Based on the well-established phase-amplitude coupling (PAC) mechanism driving information processing in the visual system, we designed a novel directionally tuned cf-tACS protocol. Directionality of information flow was inferred from the area receiving low-frequency tACS (e.g., V1) projecting onto the area receiving high-frequency tACS (e.g., MT), in this case, promoting bottom-up information flow (Forward-tACS). The control condition promoted the opposite top-down connection (from MT to V1, called Backward-tACS), both compared to a Sham-tACS condition. Task performance and EEG activity were recorded from 45 young healthy subjects. An additional cohort of 16 stroke patients with occipital lesions and impairing visual processing was measured to assess the influence of a V1 lesion on the modulation of V1-MT coupling. RESULTS: The results indicate that Forward cf-tACS successfully modulated bottom-up PAC (V1 α-phase-MT É£-amplitude) in both cohorts, while producing opposite effects on the reverse MT-to-V1 connection. Backward-tACS did not change V1-MT PAC in either direction in healthy participants but induced a slight decrease in bottom-up PAC in stroke patients. However, these changes in inter-areal coupling did not translate into cf-tACS-specific behavioural improvements. CONCLUSIONS: Single session cf-tACS can alter inter-areal coupling in intact and lesioned brains but is probably not enough to induce longer-lasting behavioural effects in these cohorts. This might suggest that a longer daily visual training protocol paired with tACS is needed to unveil the relationship between externally applied oscillatory activity and behaviourally relevant brain processing.

Stroke Recovery-Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition.

BACKGROUND: Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. METHODS: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. RESULTS: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. CONCLUSIONS: The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

Differential Impact of Brain Network Efficiency on Poststroke Motor and Attentional Deficits.

BACKGROUND: Most studies on stroke have been designed to examine one deficit in isolation; yet, survivors often have multiple deficits in different domains. While the mechanisms underlying multiple-domain deficits remain poorly understood, network-theoretical methods may open new avenues of understanding. METHODS: Fifty subacute stroke patients (7±3days poststroke) underwent diffusion-weighted magnetic resonance imaging and a battery of clinical tests of motor and cognitive functions. We defined indices of impairment in strength, dexterity, and attention. We also computed imaging-based probabilistic tractography and whole-brain connectomes. To efficiently integrate inputs from different sources, brain networks rely on a rich-club of a few hub nodes. Lesions harm efficiency, particularly when they target the rich-club. Overlaying individual lesion masks onto the tractograms enabled us to split the connectomes into their affected and unaffected parts and associate them to impairment. RESULTS: We computed efficiency of the unaffected connectome and found it was more strongly correlated to impairment in strength, dexterity, and attention than efficiency of the total connectome. The magnitude of the correlation between efficiency and impairment followed the order attention>dexterity ≈ strength (strength: |r|=.03, P=0.02, dexterity: |r|=.30, P=0.05, attention: |r|=.55, P<0.001). Network weights associated with the rich-club were more strongly correlated to efficiency than non-rich-club weights. CONCLUSIONS: Attentional impairment is more sensitive to disruption of coordinated networks between brain regions than motor impairment, which is sensitive to disruption of localized networks. Providing more accurate reflections of actually functioning parts of the network enables the incorporation of information about the impact of brain lesions on connectomics contributing to a better understanding of underlying stroke mechanisms.

Inter-Task Transfer of Prism Adaptation through Motor Imagery.

Prism adaptation (PA) is a useful method to investigate short-term sensorimotor plasticity. Following active exposure to prisms, individuals show consistent after-effects, probing that they have adapted to the perturbation. Whether after-effects are transferable to another task or remain specific to the task performed under exposure, represents a crucial interest to understand the adaptive processes at work. Motor imagery (MI, i.e., the mental representation of an action without any concomitant execution) offers an original opportunity to investigate the role of cognitive aspects of motor command preparation disregarding actual sensory and motor information related to its execution. The aim of the study was to test whether prism adaptation through MI led to transferable after-effects. Forty-four healthy volunteers were exposed to a rightward prismatic deviation while performing actual (Active group) versus imagined (MI group) pointing movements, or while being inactive (inactive group). Upon prisms removal, in the MI group, only participants with the highest MI abilities (MI+ group) showed consistent after-effects on pointing and, crucially, a significant transfer to throwing. This was not observed in participants with lower MI abilities and in the inactive group. However, a direct comparison of pointing after-effects and transfer to throwing between MI+ and the control inactive group did not show any significant difference. Although this interpretation requires caution, these findings suggest that exposure to intersensory conflict might be responsible for sensory realignment during prism adaptation which could be transferred to another task. This study paves the way for further investigations into MI's potential to develop robust sensorimotor adaptation.

Does anodal cerebellar tDCS boost transfer of after-effects from throwing to pointing during prism adaptation?

Prism Adaptation (PA) is a useful method to study the mechanisms of sensorimotor adaptation. After-effects following adaptation to the prismatic deviation constitute the probe that adaptive mechanisms occurred, and current evidence suggests an involvement of the cerebellum at this level. Whether after-effects are transferable to another task is of great interest both for understanding the nature of sensorimotor transformations and for clinical purposes. However, the processes of transfer and their underlying neural substrates remain poorly understood. Transfer from throwing to pointing is known to occur only in individuals who had previously reached a good level of expertise in throwing (e.g., dart players), not in novices. The aim of this study was to ascertain whether anodal stimulation of the cerebellum could boost after-effects transfer from throwing to pointing in novice participants. Healthy participants received anodal or sham transcranial direction current stimulation (tDCS) of the right cerebellum during a PA procedure involving a throwing task and were tested for transfer on a pointing task. Terminal errors and kinematic parameters were in the dependent variables for statistical analyses. Results showed that active stimulation had no significant beneficial effects on error reduction or throwing after-effects. Moreover, the overall magnitude of transfer to pointing did not change. Interestingly, we found a significant effect of the stimulation on the longitudinal evolution of pointing errors and on pointing kinematic parameters during transfer assessment. These results provide new insights on the implication of the cerebellum in transfer and on the possibility to use anodal tDCS to enhance cerebellar contribution during PA in further investigations. From a network approach, we suggest that cerebellum is part of a more complex circuitry responsible for the development of transfer which is likely embracing the primary motor cortex due to its role in motor memories consolidation. This paves the way for further work entailing multiple-sites stimulation to explore the role of M1-cerebellum dynamic interplay in transfer.

Toward individualized medicine in stroke-The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke.

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.

Evaluation of a shortened version of the Action Research Arm Test (ARAT) for upper extremity function after stroke: The Mini-ARAT.

OBJECTIVES: (i) to create a shortened version of the Action Research Arm Test scale, (ii) to investigate its psychometric properties compared to the original scale and (iii) to externally validate it within an independent cohort. DESIGN: Prospective longitudinal cohort study. SETTINGS: Two University Hospitals (France, Switzerland). PARTICIPANTS: 47 patients with poststroke motor deficits of the upper limb coming from two different sites were included and divided into two cohorts (n = 22 for the construction cohort; n = 25 for the validation cohort). MAIN MEASURES: We used the first cohort to build the Mini-ARAT by shortening the Action Research Arm Test scale on the basis of ceiling/floor effects and collinearity of the subscales. We studied its reliability, validity, and responsiveness and performed an external validation with the second cohort. RESULTS: The Mini-ARAT consisted of 2 subscales from the original Action Research Arm Test scale (Grip and Pinch). Internal consistency (α = 87) and inter-rater reliability (0.99, 95% CI: 0.98-0.99, p < 0.01) were good and similar to those of the Action Research Arm Test scale. The Minimal Clinically Important Difference of the Mini-ARAT was 9 points. The predictive validity in the construction and validation cohorts showed good correlation between the Mini-ARAT at baseline and the Fugl Meyer at 3 months (rho, 95% CI: 0.77, 0.49-0.90, p < 0.01, and 0.58, 0.19-0.96, p < 0.01). CONCLUSION: The Mini-ARAT is a time-effective tool able to capture the dynamics of motor deficits with high reliability and consistency, providing excellent information about residual motor functions, which is critically important for clinical and research purposes.

Non-invasive brain stimulation shows possible cerebellar contribution in transfer of prism adaptation after-effects from pointing to throwing movements.

Whether sensorimotor adaptation can be generalized from one context to others represents a crucial interest in the field of neurological rehabilitation. Nonetheless, the mechanisms underlying transfer to another task remain unclear. Prism Adaptation (PA) is a useful method employed both to study short-term plasticity and for rehabilitation. Neuro-imaging and neuro-stimulation studies show that the cerebellum plays a substantial role in online control, strategic control (rapid error reduction), and realignment (after-effects) in PA. However, the contribution of the cerebellum to transfer is still unknown. The aim of this study was to test whether interfering with the activity of the cerebellum affected transfer of prism after-effects from a pointing to a throwing task. For this purpose, we delivered cathodal cerebellar transcranial Direct Current Stimulation (tDCS) to healthy participants during PA while a control group received cerebellar Sham Stimulation. We assessed longitudinal evolutions of pointing and throwing errors and pointing trajectories orientations during pre-tests, exposure and post-tests. Results revealed that participants who received active cerebellar stimulation showed (1) altered error reduction and pointing trajectories during the first trials of exposure; (2) increased magnitude but reduced robustness of pointing after-effects; and, crucially, (3) slightly altered transfer of after-effects to the throwing task. Therefore, the present study confirmed that cathodal cerebellar tDCS interferes with processes at work during PA and provides evidence for a possible contribution of the cerebellum in after-effects transfer.

Prism Adaptation in M1.

During prism adaptation (PA), active exposure to an optical shift results in sustained modifications of the sensorimotor system, which have been shown to expand to the cognitive level and serve as a rehabilitation technique for spatial cognition disorders. Several models based on evidence from clinical and neuroimaging studies offered a description of the cognitive and the neural correlates of PA. However, recent findings using noninvasive neurostimulation call for a reexamination of the role of the primary motor cortex (M1) in PA. Specifically, recent studies demonstrated that M1 stimulation reactivates previously vanished sensorimotor changes 1 day after PA, induces after-effect strengthening, and boosts therapeutic effects up to the point of reversing treatment-resistant unilateral neglect. Here, we articulate findings from clinical, neuroimaging, and noninvasive brain stimulation studies to show that M1 contributes to acquiring and storing PA, by means of persisting latent changes after the behavioral training is terminated, consistent with studies on other sensorimotor adaptation procedures. Moreover, we describe the hierarchical organization as well as the timing of PA mechanisms and their anatomical correlates, and identify M1 as an anatomo-functional interface between low- and high-order PA-related mechanisms.

Inter-task transfer of prism adaptation depends on exposed task mastery.

The sensorimotor system sets up plastic alterations to face new demands. Terms such as adaptation and learning are broadly used to describe a variety of processes underlying this aptitude. The mechanisms whereby transformations acquired to face a perturbation generalize to other situations or stay context-dependent remain weakly understood. Here, we compared the performance of hand pointing vs throwing to visual targets while facing an optical shift of the visual field (prismatic deviation). We found that the transfer of compensations was conditioned by the task performed during exposure to the perturbation: compensations transferred from pointing to throwing but not at all from throwing to pointing. Additionally, expertise on the task performed during exposure had a marked influence on the amount of transfer to the non-exposed task: throwing experts (dart players) remarkably transferred compensations to the pointing task. Our results reveal that different processes underlying these distinct transfer properties may be at work to face a given perturbation. Their solicitation depends on mastery for the exposed task, which is responsible for different patterns of inter-task transfer. An important implication is that transfer properties, and not only after-effects, should be included as a criterion for adaptation. At the theoretical level, we suggest that tasks may need to be mastered before they can be subjected to adaptation, which has new implications for the distinction between learning and adaptation.

Do prism and other adaptation paradigms really measure the same processes?

Sensorimotor plasticity allows the nervous system to set up appropriate motor and sensory compensations when individuals face changing demands in a given motor task. A much-debated question in neuroscience research is the identification of processes that encompass this capacity of plasticity. Prism adaptation is the oldest experimental paradigm that has been used to achieve this goal (Helmholtz, 1867). Since 1990's, other paradigms have emerged such as visuomotor rotations or dynamical perturbations (inertial Coriolis forces, velocity-dependent force-field). We compared these paradigms with respect to three specific methodological features: application of the perturbation, after-effects, and generalization. This work aimed to shed light on the following central issue: Do all these paradigms involve similar processes? We used generalization properties-a relevant feature associated with the credit assignment problem-to emphasize the involvement of different processes in "adaptation" paradigms. We therefore classified these processes based on the context specificity of elicited transformations. This review reveals that the processes involved are closely linked to paradigm-related experimental conditions. Context-independent processes appear to be favored when errors are attributed to our own sensorimotor performance (prism, Coriolis) whereas context-dependent processes appear to be mostly mediated by attribution of errors to a specific external interface (visuomotor rotation, force-field). This work encourages researchers to consider the methodological aspects specific to each paradigm for future investigations of sensorimotor plasticity.