Prognostic value of changes in resting-state functional connectivity patterns in cognitive recovery after stroke: A 3T fMRI pilot study.

Resting-state studies conducted with stroke patients are scarce. First objective was to explore whether patients with good cognitive recovery showed differences in resting-state functional patterns of brain activity when compared to patients with poor cognitive recovery. Second objective was to determine whether such patterns were correlated with cognitive performance. Third objective was to assess the existence of prognostic factors for cognitive recovery. Eighteen right-handed stroke patients and eighteen healthy controls were included in the study. Stroke patients were divided into two groups according to their cognitive improvement observed at three months after stroke. Probabilistic independent component analysis was used to identify resting-state brain activity patterns. The analysis identified six networks: frontal, fronto-temporal, default mode network, secondary visual, parietal, and basal ganglia. Stroke patients showed significant decrease in brain activity in parietal and basal ganglia networks and a widespread increase in brain activity in the remaining ones when compared with healthy controls. When analyzed separately, patients with poor cognitive recovery (n=10) showed the same pattern as the whole stroke patient group, while patients with good cognitive recovery (n=8) showed increased activity only in the default mode network and fronto-temporal network, and decreased activity in the basal ganglia. We observe negative correlations between basal ganglia network activity and performance in Semantic Fluency test and Part A of the Trail Making Test for patients with poor cognitive recovery. A reverse pattern was observed between frontal network activity and the above mentioned tests for the same group. .

Transcranial ultrasound stimulation modulates the interhemispheric balance of excitability in human motor cortex.

Background. Low-intensity transcranial ultrasound stimulation (TUS) could induce both immediate and long-lasting neuromodulatory effects in human brains. Interhemispheric imbalance at prefrontal or motor cortices generally associates with various cognitive decline in aging and mental disorders. However, whether TUS could modulate the interhemispheric balance of excitability in human brain remains unknown.Objective. This study aims to explore whether repetitive TUS (rTUS) intervention can modulate the interhemispheric balance of excitability between bilateral motor cortex (M1) in healthy subjects.Approach. Motor evoked potentials (MEPs) at bilateral M1 were measured at 15 min and 0 min before a 15 min active or sham rTUS intervention on left M1 and at 0 min, 15 min and 30 min after the intervention, and the Chinese version of brief neurocognitive test battery (C-BCT) was conducted before and after the intervention respectively. Cortical excitability was quantified by MEPs, and the long-lasting changes of MEP amplitude was used as an index of plasticity.Results. In the active rTUS group (n= 20), the ipsilateral MEP amplitude increased significantly compared with baselines and lasted for up to 30 min after intervention, while the contralateral MEP amplitude decreased lasting for 15 min, yielding increased laterality between bilateral MEPs. Furthermore, rTUS intervention induced changes in some C-BCT scores, and the changes of scores correlated with the changes of MEP amplitudes induced by rTUS intervention. The sham rTUS group (n= 20) showed no significant changes in MEPs and C-BCT scores. In addition, no participants reported any adverse effects during and after the rTUS intervention, and no obvious temperature increase appeared in skull or brain tissues in simulation.Significance. rTUS intervention modulated the plasticity of ipsilateral M1 and the interhemispheric balance of M1 excitability in human brain, and improved cognitive performance, suggesting a considerable potential of rTUS in clinical interventions.

May Dual Transcranial Direct Current Stimulation Enhance the Efficacy of Robot-Assisted Therapy for Promoting Upper Limb Recovery in Chronic Stroke?

OBJECTIVE: To assess whether dual transcranial direct current stimulation (tDCS) may enhance the efficacy of exoskeleton robotic training on upper limb motor functions in patients with chronic stroke. METHODS: A prospective, bi-center, double-blind, randomized clinical trial study was performed. Patients with moderate-to-severe stroke (according to The National Institute of Health Stroke Scale) were randomly assigned to receive dual or sham tDCS immediately before robotic therapy (10 sessions, 2 weeks). The primary outcome was the Fugl-Meyer for Upper Extremity, assessed before, after, and at the 12-week follow-up. Neurophysiological evaluation of corticospinal projections to upper limb muscles was performed by recording motor evoked potentials (MEPs). ClinicalTrials.gov-NCT03026712. RESULTS: Two hundred and sixty individuals were tested for eligibility, of which 80 were enrolled and agreed to participate. Excluding 14 dropouts, 66 patients were randomly assigned into the 2 groups. Results showed that chronic patients were stable before treatment and significantly improved after that. The records within subject improvements were not significantly different between the 2 groups. However, a post-hoc analysis subdividing patients in 2 subgroups based on the presence or absence of MEPs at the baseline showed a significantly higher effect of real tDCS in patients without MEPs when compared to patients with MEPs (F = 4.6, P = .007). CONCLUSION: The adjunction of dual tDCS to robotic arm training did not further enhance recovery in the treated sample of patients with chronic stroke. However, a significant improvement in the subgroup of patients with a severe corticospinal dysfunction (as suggested by the absence of MEPs) suggests that they could benefit from such a treatment combination.

Novel TMS-EEG indexes to investigate interhemispheric dynamics in humans.

OBJECTIVE: To validate two indexes of interhemispheric signal propagation (ISP) and balance (IHB) by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG). METHODS: We used TMS-EEG to non-invasively stimulate the two hemispheres of 50 healthy volunteers and measured interhemispheric dynamics in terms of ISP and IHB. We repeated our evaluation after three weeks to assess the reliability of our indexes. We also tested whether our TMS-EEG measures were correlated with traditional interhemispheric inhibition (IHI), as measured with motor-evoked potentials (MEPs). RESULTS: Our main results showed that ISP and IHB (1) have a high reproducibility among all the participants tested; (2) have a high test-retest reliability (3) are linearly correlated with IHI, as measured with MEPs. CONCLUSIONS: The main contribution of this study lies in the proposal of new TMS-EEG cortical measures of interhemispheric dynamics and in their validation in terms of intra- and inter-subject reliability. We also provide the first demonstration of the correlation between ISP and IHI. SIGNIFICANCE: Our results are relevant for the investigation of interhemispheric dynamics in clinical populations where MEPs are not reliable.

Differential corticomotor mechanisms of ankle motor control in post stroke individuals with and without motor evoked potentials.

OBJECTIVE: Deficits in ankle motor control has been identified as a significant contributor to impaired walking after stroke. Corticomotor excitability has been related to impaired upper limb motor control and poor recovery in stroke, however contributions to lower limb function are still unclear. This study used transcranial magnetic stimulation (TMS) to determine the influence of corticomotor characteristics on lower limb motor control in chronic stroke survivors. METHODS: This retrospective study assessed 28 individuals with post stroke hemiparesis. Motor evoked potentials (MEP) measured from the paretic and non-paretic tibialis anterior (TA) muscles were used to calculate corticomotor excitability symmetry (CMEsym) and relative ipsilateral corticomotor excitability (ICE). Participants were assigned to MEP+ and MEP- groups depending on the presence (+) or absence (-) of MEPs. Ankle motor control was quantified by the ability of participants to track a sinusoidal target using dorsiflexion-plantarflexion movements of the paretic ankle and tracking error was calculated using root mean square error (RMSE). RESULTS: Multiple linear regression model for all participants revealed only CMEsym and FMLE (p < 0.01) to significantly predict RMSE. In the MEP+ group, CMEsym significantly predicted RMSE (p = 0.03) while FMLE (p = 0.02) was a significant predictor for the MEP-. CONCLUSION: Our results indicate that CMEsym between the ipsilesional and contralesional hemispheres does not necessarily translate to better paretic ankle motor control in chronic stroke. Presence or absence of a MEP in the TA muscle did not affect the ankle tracking performance, however, it was noted that different strategies maybe used by those with and without a MEP.

Transcranial direct current stimulation to the parietal cortex in hemispatial neglect: A feasibility study.

OBJECTIVES: Prior research suggests that dampening neural activity of the intact, presumably overactive hemisphere, combined with increasing neural activity in the damaged hemisphere, might restore cortical interhemispheric balance and reduce neglect. In the present study we repeatedly applied a relatively new technique, transcranial direct current stimulation (tDCS), to the posterior parietal cortex to modulate spontaneous neural activity levels in a polarity dependent fashion to find evidence for improvements in severe hemispatial neglect in chronic patients. METHODS: Eighty-nine patients were initially identified from our databases as having neglect, after thoroughly screening databases, consulting medical practitioners and baseline testing, only five met our inclusion criteria and agreed to participate. Sixty-five patients were excluded as they did not meet safety criteria for tDCS (epilepsy, metal implants), suffered from other medical conditions (i.e., heart disease, epilepsy, current psychiatric disorder) or displayed only mild neglect at baseline testing. Five patients with severe chronic hemispatial neglect were enrolled in a double-blind, placebo-controlled treatment program. TDCS or placebo was applied for 20 minutes over the left (cathodal) and right (anodal) posterior parietal cortex at an intensity of 2 mA on five consecutive days. Treatment conditions were separated by a four week wash-out period. Baseline corrected change in performance on the conventional subtests of the Behavioral Inattention Test (BIT) was our primary endpoint. RESULTS: No treatment-related effects were observed for the BIT change scores and performance on individual subtests. Moreover, patients' performance somewhat improved only during the stimulation period (day one vs day five, irrespective of whether it was placebo or tDCS), but not thirty days later, indicating a practice effect. DISCUSSION: The present study does not provide evidence that tDCS to the posterior parietal cortex improves chronic hemispatial neglect. As a result of in- and exclusion health and safety criteria the majority of patients were excluded, which indicates that performing large randomized controlled trials is not feasible in chronic neglect patients.

Contralesional rTMS relieves visual extinction in chronic stroke.

Patients affected by right parietal lobe lesion can be severely impaired in sustained attention tasks, particularly in the left visual field. For example, patients with right parietal stroke are commonly limited in their ability to attentionally track multiple moving objects in their left visual field when competing stimuli are simultaneously presented in the right, ipsilesional visual field. This is a hallmark of visual extinction, a failure to respond to contralesional visual stimuli, when competing stimuli are presented in the good hemifield. It has been hypothesized that post-stroke hyperactivity of the undamaged left hemisphere leads to excessive cross-hemispheric inhibition of the damaged right hemisphere, thus exacerbating the attentional deficits. However, there has been no direct physiological demonstration of this hypothesis, as most of the studies are conducted using unilateral tasks, a condition not sufficient to drive inter-hemispheric competition. The inter-hemispheric inhibition hypothesis also raises the possibility that if hyperactivity of the healthy hemisphere were reduced, this could relieve inter-hemispheric inhibition, disinhibiting the damaged hemisphere and potentially restoring some function. To test this hypothesis, and to examine whether we could relieve deficits in sustained attention in right parietal patients, we used repetitive transcranial magnetic stimulation (rTMS) to reduce the activity of the left, healthy hemisphere. Six patients suffering from visual extinction underwent two counterbalanced sessions: low frequency rTMS over the left parietal lobe and sham control stimulation. The patients' performance in an attentional tracking task significantly improved in the contralesional visual field immediately after rTMS, but not after sham. Performance remained unaltered in the ipsilesional field. We hypothesize that rTMS temporarily releases the damaged right hemisphere from excessive cross-hemispheric inhibition by the hyperactive healthy hemisphere, leading to some cognitive recovery after cortical lesion.

Interhemispheric balance in Parkinson's disease: a transcranial magnetic stimulation study.

BACKGROUND: Parkinson's disease (PD) is characterized by various changes in motor excitability. OBJECTIVE: To examine through Transcranial Magnetic Stimulation (TMS) cortical excitability, specifically addressing interhemispheric connections in PD. METHODS: Nineteen PD patients with a predominant involvement of the left hemibody (7 females, age 61.7 years,) and 13 controls (6 females, age 61.5 years) entered the study. Patients were subdivided into two groups (early and advanced) according to the time from PD diagnosis. Participants underwent evaluation of Resting Motor Threshold (RMT) and ipsilateral Silent Period (iSP), induced by suprathreshold TMS on the ipsilateral-M1, measured as suppression of voluntary EMG activity. Mirror Movements (MM) were EMG-recorded and scored, in three upper limb muscles, during unilateral voluntary hand movement. Patients were studied at baseline (OFF drug) and after acute levodopa challenge (ON). RESULTS: PD patients showed a general reduction in RMT vs controls (P < 0.01 for right and left hemisphere) in both drug conditions. Early PD had a significantly lower RMT over the right vs the left hemisphere (P = 0.027); this difference was no longer significant after levodopa. In early PD patients, MM were mainly observed in the right arm during voluntary activation of the left, more affected side both in OFF (P = 0.033) and in ON (P = 0.046). In PD, RMT of the left, less affected M1 was significantly correlated with the right lateralized motor score (P = 0.011; Spearman's coefficient = -0.585), as well as with disease duration. In PD patients, a shorter (P = 0.039) and smaller (P = 0.037) iSP was detected when the stimulus was applied to the worse M1 (right) compared with the contralateral side. This asymmetry was significant only OFF drug. In the PD group iSP-duration from the right, less affected APB was negatively correlated with the MM recorded from the same side during the voluntary movement of the worse side (Spearman's coefficient = -0.498; P = 0.035). CONCLUSIONS: Increased cortical motor excitability in PD, consistent with previous findings, is more evident in the worse hemisphere, particularly in early PD. Asymmetric motor involvement is also associated with excessive involuntary mirroring and defective interhemispheric inhibition, both unfavoring the more affected side. Altogether, these findings suggest that asymmetric motor involvement in PD, particularly in the earlier phases of the disease, affects the interhemispheric balance of cortical excitability, movement lateralization and transcallosal inhibition.