Pierre Nicolo

Coherent neural oscillations predict future motor and language improvement after stroke

Recent findings have demonstrated that stroke lesions affect neural communication in the entire brain. However, it is less clear whether network interactions are also relevant for plasticity and repair. This study investigated whether the coherence of neural oscillations at language or motor nodes is associated with future clinical improvement. Twenty-four stroke patients underwent high-density EEG recordings and standardized motor and language tests at 2-3 weeks (T0) and 3 months (T1) after stroke onset. In addition, EEG and motor assessments were obtained from a second population of 18 stroke patients. The graph theoretical measure of weighted node degree at language and motor areas was computed as the sum of absolute imaginary coherence with all other brain regions and compared to the amount of clinical improvement from T0 to T1. At T0, beta-band weighted node degree at the ipsilesional motor cortex was linearly correlated with better subsequent motor improvement, while beta-band weighted node degree at Brocas area was correlated with better language improvement. Clinical recovery was further associated with contralesional theta-band weighted node degree. These correlations were each specific to the corresponding brain area and independent of initial clinical severity, age, and lesion size. Findings were reproduced in the second stroke group. Conversely, later coherence increases occurring between T0 and T1 were associated with less clinical improvement. Improvement of language and motor functions after stroke is therefore associated with inter-regional synchronization of neural oscillations in the first weeks after stroke. A better understanding of network mechanisms of plasticity may lead to new prognostic biomarkers and therapeutic targets.See Ward (doi:10.1093/brain/awv265) for a scientific commentary on this article.

Predicting motor improvement after stroke with clinical assessment and diffusion tensor imaging

Reliable predictors of motor improvement in individual patients after stroke are scarce. Acute determination of upper limb Fugl-Meyer assessment (FMA) appears to have predictive value.1,2 This approach predicts that patients will improve approximately 70% of the difference between the maximum upper extremity FMA score and the score first tested for a given individual (recovery-typical). However, a significant subset of patients improves much less than predicted (recovery-atypical). Alternative models using other techniques like diffusion tensor imaging (DTI)3,4 also fail to predict recovery in some patients. Here, we show that a combination of FMA and DTI obtained in the first weeks after stroke accurately discriminate between recovery-typical and recovery-atypical patients. In addition, we identify an alternative set of model parameters required for predictions in the recovery-atypical subgroup.

Variability of behavioural responses to transcranial magnetic stimulation: Origins and predictors.

Transcranial magnetic stimulation (TMS) may modulate the excitability of local cortical stimulation sites and distant functionally interconnected regions for minutes, hours or even days. The effects of TMS suggest that it not only acts on activity of the stimulated area, but also on its connections with remote areas. Due to these properties one of the main rationales for the application of TMS in stroke patients is to improve imbalance in interhemispheric inhibition. However, given that TMS may have excitatory or inhibitory effects the impact of stimulation is not easy to predict. In this review, we discuss the different factors that determine the magnitude and quality of physiological and behavioural responses to TMS. Whether TMS is mainly excitatory or inhibitory not only depends on the parameters of stimulation such as pulse frequency and duration, but also on baseline activity of neural tissue before stimulation, or even on cognitive factors such as attention. A major challenge for the application of TMS as therapy method is to identify predictors of positive effects in individual patients. Neuroimaging studies measuring hemodynamic or electrophysiological responses show that changes in interhemispheric competition or adaptations of functional networks in patients with focal brain lesions may predict the individual response to brain stimulation. Such techniques have the potential to select the most appropriate among different intervention methods for an individual patient.

Longitudinal Structural and Functional Differences Between Proportional and Poor Motor Recovery After Stroke

Background. Evolution of motor function during the first months after stroke is stereotypically bifurcated, consisting of either recovery to about 70% of maximum possible improvement (“proportional recovery, PROP”) or in little to no improvement (“poor recovery, POOR”). There is currently no evidence that any rehabilitation treatment will prevent POOR and favor PROP. Objective. To perform a longitudinal and multimodal assessment of functional and structural changes in brain organization associated with PROP. Methods. Fugl-Meyer Assessments of the upper extremity and high-density electroencephalography (EEG) were obtained from 63 patients, diffusion tensor imaging from 46 patients, at 2 and 4 weeks (T0) and at 3 months (T1) after stroke onset. Results. We confirmed the presence of 2 distinct recovery patterns (PROP and POOR) in our sample. At T0, PROP patients had greater integrity of the corticospinal tract (CST) and greater EEG functional connectivity (FC) between the affected hemisphere and rest of the brain, in particular between the ventral premotor and the primary motor cortex. POOR patients suffered from degradation of corticocortical and corticofugal fiber tracts in the affected hemisphere between T0 and T1, which was not observed in PROP patients. Better initial CST integrity correlated with greater initial global FC, which was in turn associated with less white matter degradation between T0 and T1. Conclusions. These findings suggest links between initial CST integrity, systems-level cortical network plasticity, reduction of white matter atrophy, and clinical motor recovery after stroke. This identifies candidate treatment targets.

Neurobiological Correlates of Inhibition of the Right Broca Homolog during New-Word Learning

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated beneficial effects on motor learning. It would be important to obtain a similar enhancement for verbal learning. However, previous studies have mostly assessed short-term effects of rTMS on language performance and the effect on learning is largely unknown. This study examined whether an inhibition of the right Broca homolog has long-term impact on neural processes underlying the acquisition of new words in healthy individuals. Sixteen young participants trained a new-word learning paradigm with rare, mostly unknown objects and their corresponding words immediately after continuous theta burst stimulation (cTBS) or sham stimulation of right inferior frontal gyrus (IFG) in a cross-over design. Neural effects were assessed with electroencephalography (EEG) source power analyses during the naming task as well as coherence analyses at rest 1 day before and after training. Inhibition of the right Broca homolog did not affect new word learning performance at the group level. Behavioral and neural responses to cTBS were variable across participants and were associated with the magnitude of resting-state alpha-band coherence between the stimulated area and the rest of the brain before stimulation. Only participants with high intrinsic alpha-band coherence between the stimulated area and the rest of the brain before stimulation showed the expected inhibition during naming and greater learning performance. In conclusion, our study confirms that cTBS can induce lasting modulations of neural processes which are associated with learning, but the effect depends on the individual network state.

Evolution of Cortical Asymmetry with Post-stroke Rehabilitation: A Pilot Study

The lesions induced by unilateral strokes perturb the complex and critical interhemispheric balance. While a high asymmetry measured in the acute phase is known to be a predictor for poor motor recovery, the evolution of this imbalance along motor recovery has not been studied. Here, we evaluated the evolution of the cortical power asymmetry during a robot-assisted motor task along a rehabilitation intervention. Preliminary results suggest that a reduction of the brain asymmetry towards values exhibited by healthy controls is associated with higher motor recovery.

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

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.

Training Muscle Synergies to Relearn Movement: Current Perspectives and Future Trends

The integrity of muscle synergies patterns has been proposed as a physiological marker of cortical damage but how to modify and train muscle synergies to relearn movement is still an open question. Here we present our recent results about the modifications that the forces induced by robots can cause on upper limb muscle synergies after stroke. Our results show that a single exposure to forces provided by a robotic device can impact muscle synergies activation. Moreover, a prolonged robot-aided motor training can promote an enduring longitudinal reorganization of upper limb muscle synergies. Finally, we discuss the application of muscle synergies in neurorehabilitation to both assess the effectiveness of treatments and design novel protocols.

Personalizing Exoskeleton-Based Upper Limb Rehabilitation Using a Statistical Model: A Pilot Study

Clinical studies have so far not been able to show if robotic therapy is superior to conventional methods. The personalization of robot-assisted therapy according to the individual motor deficits might contribute to reach this goal. Here we present a statistical approach to automatically personalize robotic rehabilitation. Our method uses different motor performance measures to estimate motor improvement and adapt the motor task within a treatment session. This approach was tested with a pilot sub-acute stroke patient and the outcome was compared to a similar patient who underwent conventional physical therapy. Pilot results showed better outcomes in clinical tests, kinematics and muscle activity for the subject who trained using the personalized robotic approach.

Transcranial direct current stimulation reduces secondary white-matter degradation after stroke

Recent studies demonstrated that stroke patients with large lesion to the cortico-spinal tract (CST) show secondary degradation of ipsilesional white matter tracts and poor motor recovery (POOR) in the subacute period. This suggests that white matter preservation might be an interesting target for this group of patients and might help improve motor outcome. Non-invasive brain stimulation (NIBS) can boost motor function in stroke patients, but we lack information on its impact on white matter microstructure. Therefore, we conducted a randomized controlled trial comparing the effects of cathodal transcranial direct current stimulation (ca-tDCS), continuous theta burst stimulation (cTBS), or sham stimulation on white matter degradation and motor improvement, as measured with Diffusion Tensor Imaging (DTI) and standardised motor assessments. Results showed preserved structural connectivity after ca-tDCS compared with the other experimental groups in POOR patients. This correlated with better clinical recovery.