Differential Relationship between Microstructural Integrity in White Matter Tracts and Motor Recovery following Stroke Based on Brain-Derived Neurotrophic Factor Genotype.

Objective: The relationship between white matter integrity and the brain-derived neurotrophic factor (BDNF) genotype and its effects on motor recovery after stroke are poorly understood. We investigated the values of fractional anisotropy (FA) in the corticospinal tract (CST), the intrahemispheric connection from the primary motor cortex to the ventral premotor cortex (M1PMv), and the interhemispheric connection via the corpus callosum (CC) in patients with the BDNF genotype from the acute to the subacute phase after stroke. Methods: The Fugl-Meyer assessment, upper extremity (FMA-UE), and tract-related FA were assessed at 2 weeks (T1) and 3 months (T2) after stroke using diffusion tensor imaging (DTI). Fifty-eight patients diagnosed with ischemic stroke were classified according to the BDNF genotype into a Val (valine homozygotes) or Met (methionine heterozygotes and homozygotes) group. Results: The Val group exhibited a larger reduction of FA values in the ipsilesional M1PMv than the Met group from T1 to T2. The FMA-UE at T2 was negatively correlated with FA of the contralesional M1PMv at T2 in the Val group but was positively correlated with FA of the ipsilesional CST and CC at T2 in the Met group. Conclusions: The integrity of the intra- and interhemispheric connections might be related to different processes of motor recovery dependent on the BDNF genotype. Thus, the BDNF genotype may need to be considered as a factor influencing neuroplasticity and functional recovery in patients with stroke. This trial is registered with http://www.clinicaltrials.gov: NCT03647787.

Effects of Process-Based Cognitive Training on Memory in the Healthy Elderly and Patients with Mild Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: This study investigated the effects of process-based cognitive training that targets working memory and cognitive control on memory improvement in healthy elderly individuals and patients with mild cognitive impairment (MCI). METHODS: Forty healthy subjects and 40 patients with MCI were randomly assigned to either the intervention or control group. The intervention group received 12 sessions of designated cognitive training. The control group did not receive cognitive training. A memory test was administered pre-intervention, post-intervention, and 4 weeks after the intervention. Additional comprehensive neuropsychological tests were also administered including a depression scale questionnaire. RESULTS: Performance in attention and working memory, which are directly related to the training domains, and global cognitive function were improved in the intervention group after training. In memory tests, interference by irrelevant stimuli was reduced and recognition memory was improved after the intervention. Furthermore, cognitive training ameliorated depressive symptoms. These training effects were not dependent on MCI status. CONCLUSION: Process-based cognitive training that targets working memory and cognitive control effectively improves memory processes including retrograde interference and recognition, as well as depressive symptoms associated with aging in healthy elderly individuals and patients with MCI.

Prediction of motor recovery using indirect connectivity in a lesion network after ischemic stroke.

BACKGROUND: Recovery prediction can assist in the planning for impairment-focused rehabilitation after a stroke. This study investigated a new prediction model based on a lesion network analysis. To predict the potential for recovery, we focused on the next link-step connectivity of the direct neighbors of a lesion. METHODS: We hypothesized that this connectivity would contribute to recovery after stroke onset. Each lesion in a patient who had suffered a stroke was transferred to a healthy subject. First link-step connectivity was identified by observing voxels functionally connected to each lesion. Next (second) link-step connectivity of the first link-step connectivity was extracted by calculating statistical dependencies between time courses of regions not directly connected to a lesion and regions identified as first link-step connectivity. Lesion impact on second link-step connectivity was quantified by comparing the lesion network and reference network. RESULTS: The lower the impact of a lesion was on second link-step connectivity in the brain network, the better the improvement in motor function during recovery. A prediction model containing a proposed predictor, initial motor function, age, and lesion volume was established. A multivariate analysis revealed that this model accurately predicted recovery at 3 months poststroke (R 2 = 0.788; cross-validation, R 2 = 0.746, RMSE = 13.15). CONCLUSION: This model can potentially be used in clinical practice to develop individually tailored rehabilitation programs for patients suffering from motor impairments after stroke.

Modulating Effects of Whole-body Vibration on Cortical Activity and Gait Function in Chronic Stroke Patients.

Whole-body vibration exercise (WBVe) can provide proper somatosensory stimulation and improve muscle strength in stroke patients. This study investigated the effects of WBVe on gait function and cortical activity in patients with chronic stroke. Thirty stroke patients were randomly assigned to either the WBVe or the control group. The WBVe group received the vibration in a half-squat position for 5 minutes at an intensity of 20 Hz. The control group kept the same posture but did not receive the vibration. Cortical activity was investigated using functional near-infrared spectroscopy (fNIRS). Gait function was assessed by a 10-m walk test (10MWT), a timed up and go (TUG) test, a Fugl-Meyer Assessment, and a Tinetti Performance-Oriented Mobility Assessment (TPOMA). In group analysis of the fNIRS data, oxygenated hemoglobin concentration was significantly increased in the ipsilesional supplementary motor area, bilateral sensorimotor cortex, and contralesional prefrontal cortex in the WBVe group compared to the control group (p < 0.05). Functional assessment demonstrated a significant interaction between time and group for the 10MWT and TUG test, suggesting that the WBVe group demonstrated meaningful improvement after intervention (p < 0.05). These results suggested that WBVe modulated the cerebral cortical activities and resulted in improvement of gait function in chronic stroke patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03375346.

Different Brain Connectivity between Responders and Nonresponders to Dual-Mode Noninvasive Brain Stimulation over Bilateral Primary Motor Cortices in Stroke Patients.

Noninvasive brain stimulation (NBS), such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS), has been used in stroke patients with motor impairment. NBS can help recovery from brain damage by modulating cortical excitability. However, the efficacy of NBS varies among individuals. To obtain insights of responsiveness to the efficacy of NBS, we investigated characteristic changes of the motor network in responders and nonresponders of NBS over the primary motor cortex (M1). A total of 21 patients with subacute stroke (13 males, mean age 59.6 ± 11.5 years) received NBS in the same manner: 1 Hz rTMS on the contralesional M1 and anodal tDCS on the ipsilesional M1. Participants were classified into responders and nonresponders based on the functional improvement of the affected upper extremity after applying NBS. Twelve age-matched healthy controls (8 males, mean age 56.1 ± 14.3 years) were also recruited. Motor networks were constructed using resting-state functional magnetic resonance imaging. M1 intrahemispheric connectivity, interhemispheric connectivity, and network efficiency were measured to investigate differences in network characteristics between groups. The motor network characteristics were found to differ between both groups. Specifically, M1 intrahemispheric connectivity in responders showed a noticeable imbalance between affected and unaffected hemispheres, which was markedly restored after NBS. The responders also showed greater interhemispheric connectivity and higher efficiency of the motor network than the nonresponders. These results may provide insight on patient-specific NBS treatment based on the brain network characteristics in neurorehabilitation of patients with stroke. This trial is registered with trial registration number NCT03390192.

Modulation of Cortical Activity by High-Frequency Whole-Body Vibration Exercise: An fNIRS Study.

CONTEXT: Whole-body vibration (WBV) has shown many positive effects on the human body in rehabilitation and clinical settings in which vibration has been used to elicit muscle contractions in spastic and paretic muscles. OBJECTIVE: The purpose of this study was to investigate whether WBV exercise (WBVe) differently modulates the cortical activity associated with motor and prefrontal function based on its frequency. METHODS: A total of 18 healthy male adults (mean age: 25.3 [2.4] y) participated in this study and performed WBVe (Galileo Advanced plus; Novotec Medical, Pforzheim, Germany) under 3 different vibration frequency conditions (4-mm amplitude with 10-, 20-, and 27-Hz frequencies) and a control condition (0-mm amplitude with 0-Hz frequency). Each condition consisted of 2 alternating tasks (squatting and standing) every 30 seconds for 5 repetitions. All subjects performed the 4 conditions in a randomized order. MAIN OUTCOME MEASURE: Cortical activation during WBVe was measured by relative changes in oxygenated hemoglobin concentration over the primary motor cortex, premotor cortex, supplementary motor area, and prefrontal and somatosensory cortices using functional near-infrared spectroscopy. RESULTS: Oxygenated hemoglobin concentration was higher during the 27-Hz vibration condition than the control and 10-Hz vibration conditions. Specifically, these changes were pronounced in the bilateral primary motor cortex (P < .05) and right prefrontal cortex (P < .05). In contrast, no significant changes in oxygenated hemoglobin concentration were observed in any of the cortical areas during the 10-Hz vibration condition compared with the control condition. CONCLUSION: This study provides evidence that the motor network and prefrontal cortical areas of healthy adult males can be activated by 27-Hz WBVe. However, WBVe at lower frequencies did not induce significant changes in cortical activation.

Relationship between Serum BDNF Levels and Depressive Mood in Subacute Stroke Patients: A Preliminary Study.

The aim of this preliminary study was to investigate the potential of serum brain-derived neurotrophic factor (BDNF) as a biomarker in poststroke depressive mood in subacute stroke patients. Thirty-eight subacute stroke patients were recruited in this study. All participants underwent the standard rehabilitation program that included 2 h of physical therapy daily and 1 h of occupational therapy five days a week. The rehabilitation period lasted two weeks during the subacute stroke phase. We measured the serum BDNF, proBDNF, and matrix metalloproteinase-9 before and one and two weeks after the standard rehabilitation program. In addition, all participants were assessed using the Geriatric Depression Scale-Short Form (GDS-SF) for depressive mood at three time points. Pearson correlation analysis was performed to determine the relationship between serum BDNF levels and the GDS-SF. The GDS-SF showed significant improvement during the standard rehabilitation program period (p < 0.05). The GDS-SF was significantly correlated with serum BDNF levels at each time point (p < 0.05). These results suggest that serum BDNF may be used as a biomarker for depressive mood in subacute stroke patients. However, further studies with larger study populations are needed to clarify these results.

Differences in motor network dynamics during recovery between supra- and infra-tentorial ischemic strokes.

Most previous stroke studies have been performed in heterogeneous patient populations. Moreover, the brain network might demonstrate different recovery dynamics according to lesion location. In this study, we investigated variation in motor network alterations according to lesion location. Forty patients with subcortical ischemic stroke were enrolled. Patients were divided into two groups: 21 patients with supratentorial stroke (STS) and 19 patients with infratentorial stroke (ITS). All patients underwent resting-state functional magnetic resonance imaging and behavioral assessment at 2 weeks and 3 months poststroke. Twenty-four healthy subjects participated as a control group. To compare altered connectivity between groups, measures used in previous studies to evaluate interhemispheric balance and global network reorganization were investigated and the relationship between network measures and motor functions were examined. Cortico-cerebellar connectivity was also extracted to investigate its relationship with interhemispheric connectivity. In the STS group, measures related to interhemispheric balance were disrupted compared to the control group 2 weeks poststroke, while this was not found in the ITS group. During recovery, measures related to global network reorganization in the STS group and measures related to interhemispheric balance in the ITS group demonstrated significant changes, respectively. Moreover, motor functions were correlated with altered network measures in both groups. There was an interactive relationship between cortico-cerebellar and interhemispheric cortical connectivity only in the ITS group. Different changes in the motor network were observed depending on the location of stroke lesions. These results might originate from differences in the interactions between cortico-cerebellar and interhemispheric connectivity.

Alteration and Role of Interhemispheric and Intrahemispheric Connectivity in Motor Network After Stroke.

This study investigated local and global changes in the motor network using longitudinal resting-state functional magnetic resonance imaging (rs-fMRI). Motor impairment was measured in 81 stroke patients using Fugl-Meyer assessment on the same day as rs-fMRI acquisition at both 2 weeks and 3 months post-stroke. The relationships between network measures and motor function scores were assessed. With regard to local connectivity, interhemispheric connectivity was noticeably altered at each time point. Interhemispheric connectivity was also related to residual motor function and improvement in motor function. The anterior intraparietal sulcus and other well-known primary and secondary motor-related regions played important roles in motor function. Changes in global connectivity according to stroke type and initial severity were investigated. In global connectivity, interhemispheric connectivity was disrupted at 2 weeks post-stroke regardless of stroke type and initial severity. During the recovery period, interhemispheric connectivity recovered well in patients with hemorrhagic stroke or low severity. In contrast, there were no significant between-group and within-group alterations in intrahemispheric connectivity. Intrahemispheric connectivity of the inferior frontal cortex (IFC) exhibited opposite alterations compared to other connections. There were no differences between groups in IFC connectivity alterations; however, decreasing ipsilesional IFC connectivity and contralesional IFC during recovery were noticeable in patients with mild to moderate impairments and patients with severe impairments, respectively. These results may be helpful in understanding the network changes that occur after stroke and could have important implications for treatment strategy development in future studies.

Modulating Brain Connectivity by Simultaneous Dual-Mode Stimulation over Bilateral Primary Motor Cortices in Subacute Stroke Patients.

Repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used for the modulation of stroke patients' motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation) over bilateral primary motor cortices (M1s) was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient's motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640.

Changes in network connectivity during motor imagery and execution.

BACKGROUND: Recent studies of functional or effective connectivity in the brain have reported that motor-related brain regions were activated during motor execution and motor imagery, but the relationship between motor and cognitive areas has not yet been completely understood. The objectives of our study were to analyze the effective connectivity between motor and cognitive networks in order to define network dynamics during motor execution and motor imagery in healthy individuals. Second, we analyzed the differences in effective connectivity between correct and incorrect responses during motor execution and imagery using dynamic causal modeling (DCM) of electroencephalography (EEG) data. METHOD: Twenty healthy subjects performed a sequence of finger tapping trials using either motor execution or motor imagery, and the performances were recorded. Changes in effective connectivity between the primary motor cortex (M1), supplementary motor area (SMA), premotor cortex (PMC), and dorsolateral prefrontal cortex (DLPFC) were estimated using dynamic causal modeling. Bayesian model averaging with family-level inference and fixed-effects analysis was applied to determine the most likely connectivity model for these regions. RESULTS: Motor execution and imagery showed inputs to distinct brain regions, the premotor cortex and the supplementary motor area, respectively. During motor execution, the coupling strength of a feedforward network from the DLPFC to the PMC was greater than that during motor imagery. During motor imagery, the coupling strengths of a feedforward network from the PMC to the SMA and of a feedback network from M1 to the PMC were higher than that during motor execution. In imagined movement, although there were connectivity differences between correct and incorrect task responses, each motor imagery task that included correct and incorrect responses showed similar network connectivity characteristics. Correct motor imagery responses showed connectivity from the PMC to the DLPFC, while the incorrect responses had characteristic connectivity from the SMA to the DLPFC. CONCLUSIONS: These findings provide an understanding of effective connectivity between motor and cognitive areas during motor execution and imagery as well as the basis for future connectivity studies for patients with stroke.

Interactions Between the Corticospinal Tract and Premotor-Motor Pathways for Residual Motor Output After Stroke.

BACKGROUND AND PURPOSE: Brain imaging has continuously enhanced our understanding how different brain networks contribute to motor recovery after stroke. However, the present models are still incomplete and do not fit for every patient. The interaction between the degree of damage of the corticospinal tract (CST) and of corticocortical motor connections, that is, the influence of the microstructural state of one connection on the importance of another has been largely neglected. METHODS: Applying diffusion-weighted imaging and probabilistic tractography, we investigated cross-network interactions between the integrity of ipsilesional CST and ipsilesional corticocortical motor pathways for variance in residual motor outcome in 53 patients with subacute stroke. RESULTS: The main finding was a significant interaction between the CST and corticocortical connections between the primary motor and ventral premotor cortex in relation to residual motor output. More specifically, the data indicate that the microstructural state of the connection primary motor-ventral premotor cortex plays only a role in patients with significant damage to the CST. In patients with slightly affected CST, this connection did not explain a relevant amount of variance in motor outcome. CONCLUSIONS: The present data show that patients with stroke with different degree of CST disruption differ in their dependency on structural premotor-motor connections for residual motor output. This finding might have important implications for future research on recovery prediction models and on responses to treatment strategies.

Synergistic but independent: The role of corticospinal and alternate motor fibers for residual motor output after stroke.

BACKGROUND: Brain imaging has shown that not only the cortico-spinal tract (CST), but also alternate corticofugal motor fibers (aMF), such as the cortico-rubro-spinal and cortico-reticulo-spinal tract, influence residual motor output after stroke. So far, studies mainly have investigated each tract separately. A combined analysis of CST and aMF with assessment of their interactive role, i.e., that structural integrity of one tract influences the functional role of the structural integrity of the other, is pending. METHODS: 39 late subacute stroke patients (aged 59.4 ± 12.0 years, 100 ± 11 days after stroke) were included. Probabilistic tractography was used to reconstruct CST and aMF. Fractional anisotropy (FA) was calculated as a measure of microstructural integrity. Multiple-linear-regression analysis was used to associate tract-related FA with residual motor output and to determine interactions between CST and aMF. RESULTS: Both CST (coefficient = 3.93, p < 0.0001) and aMF (coefficient = - 4.43, p = 0.003) of the affected hemisphere significantly contributed to residual motor output. An interaction of their impacts with a consecutive influence on motor output was not detected (p = 0.882). Thus, these data suggest that aMF and CST explain residual motor output in stroke patients in a synergistic, but mainly independent manner. CONCLUSIONS: The structural states of the CST and also - to a smaller degree - of the aMF correlate with residual motor output in late subacute stroke patients. Based on this statistical modeling with all inherent limitations, the novel finding of an absence of a significant interaction between both tracts in regard of their functional role, suggests that both corticofugal pathways act synergistically but largely independently. These findings add to the understanding of the functional role of different corticofugal motor fibers and their interactions for motor output after stroke.

Real-time measurement of cerebral blood flow during and after repetitive transcranial magnetic stimulation: A near-infrared spectroscopy study.

OBJECTIVES: To confirm the interhemispheric modulation induced by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex, real-time regional cerebral blood flow (rCBF) was assessed using functional near-infrared spectroscopy (fNIRS) in the contralateral primary motor cortex (M1) and premotor cortex (PM). METHODS: Ten right-handed healthy subjects completed two experimental sessions that were randomly arranged for real or sham rTMS session. In the real rTMS session, fNIRS data were acquired from the right M1 and PM area, while the motor hot spot of the left M1 was stimulated with 1Hz rTMS for 1200 pulses with two boosters. In the sham stimulation session, stimulation was delivered with a disconnected coil. RESULTS: During the real rTMS session, the concentration of oxyhemoglobin ([oxy-Hb]) in the right M1 increased continuously until the end of the stimulation. These changes lasted for 20min, while the right PM did not show a change in [oxy-Hb] concentration. On the other hand, the concentration of deoxy-hemoglobin ([deoxy-Hb]) decreased continuously in the right M1 and PM during the real rTMS stimulation, and this change lasted for 20min after the stimulation. The sham stimulation did not exhibit any significant change in both [oxy-Hb] and [deoxy-Hb] concentration during or after the stimulation. CONCLUSIONS: Application of 1Hz rTMS over M1 resulted in changes of rCBF in contralateral M1 and PM, which seemed to constitute a function of interhemispheric modulation of rTMS. The fNIRS data was able to detect this physiological change of neuromodulatory action of rTMS in real-time.

Association Between Brain-Derived Neurotrophic Factor Genotype and Upper Extremity Motor Outcome After Stroke.

BACKGROUND AND PURPOSE: The identification of intrinsic factors for predicting upper extremity motor outcome could aid the design of individualized treatment plans in stroke rehabilitation. The aim of this study was to identify prognostic factors, including intrinsic genetic factors, for upper extremity motor outcome in patients with subacute stroke. METHODS: A total of 97 patients with subacute stroke were enrolled. Upper limb motor impairment was scored according to the upper limb of Fugl-Meyer assessment score at 3 months after stroke. The prediction of upper extremity motor outcome at 3 months was modeled using various factors that could potentially influence this impairment, including patient characteristics, baseline upper extremity motor impairment, functional and structural integrity of the corticospinal tract, and brain-derived neurotrophic factor genotype. Multivariate ordinal logistic regression models were used to identify the significance of each factor. RESULTS: The independent predictors of motor outcome at 3 months were baseline upper extremity motor impairment, age, stroke type, and corticospinal tract functional integrity in all stroke patients. However, in the group with severe motor impairment at baseline (upper limb score of Fugl-Meyer assessment <25), the number of Met alleles in the brain-derived neurotrophic factor genotype was also an independent predictor of upper extremity motor outcome 3 months after stroke. CONCLUSIONS: Brain-derived neurotrophic factor genotype may be a potentially useful predictor of upper extremity motor outcome in patients with subacute stroke with severe baseline motor involvement.

Dual-mode noninvasive brain stimulation over the bilateral primary motor cortices in stroke patients.

BACKGROUND: Noninvasive brain stimulation (NBS) using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has recently been adopted for modulating motor function in stroke patients. OBJECTIVE: We investigated the effect of simultaneous dual-mode stimulation using rTMS and tDCS over the bilateral primary motor cortices (M1) to assess its efficacy as compared to single stimulation using rTMS for the recovery of motor function in subacute stroke patients. METHODS: Thirty subacute stroke patients were recruited in this study. In the dual-mode stimulation group, 10 Hz rTMS (90% of resting motor threshold, 1,000 pulses) was applied over the ipsilesional M1 for 20 minutes with the simultaneous application of cathodal tDCS (2 mA) on the contralesional M1. The single stimulation group underwent 10 Hz rTMS without tDCS. Ten daily sessions were conducted for two consecutive weeks. The total Fugl-Meyer (FMA-T), upper limb (FMA-UL), and lower limb (FMA-LL) scores were measured before, after, and two months later. RESULTS: The FMA-T and FMA- UL were significantly improved over time in both the dual and single stimulation group (p < 0.05). However, there were significant group and time interaction effects in both the FMA-T and FMA-UL (p < 0.05). Post-hoc analysis showed that the mean changes in the FMA-T and FMA-UL were significantly better in the dual-mode stimulation group. CONCLUSION: Dual-mode NBS with the simultaneous application of 10 Hz rTMS and cathodal tDCS over the bilateral M1s was safe and superior to 10 Hz rTMS alone for improving motor function in subacute stroke patients.

Effects of Bilateral Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysphagia.

BACKGROUND: Optimal protocol of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia remains uncertain with regard to its clinical efficacy. OBJECTIVE: The aim of the present study is to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. METHODS: This study was a single-blind, randomized controlled study with a blinded observer. Thirty-five stroke patients were randomly divided into three intervention groups: the bilateral stimulation group, the unilateral stimulation group, and the sham stimulation group. For the bilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional and 500 pulses of 10 Hz rTMS over the contralesional motor cortices over the cortical areas that project to the mylohyoid muscles were administered daily for 2 consecutive weeks. For the unilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional motor cortex over the cortical representation of the mylohyoid muscle and the same amount of sham rTMS over the contralesional hemisphere were applied. For the sham stimulation group, sham rTMS was applied at the bilateral motor cortices. Clinical swallowing function and videofluoroscopic swallowing studies were assessed before the intervention (T0), immediately after the intervention (T1) and 3 weeks after the intervention (T2) using Clinical Dysphagia Scale (CDS), Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and Videofluoroscopic Dysphagia Scale (VDS). RESULTS: There were significant time and intervention interaction effects in the CDS, DOSS, PAS, and VDS scores (p < 0.05). In the direct comparison of the changes in the swallowing parameters among the three groups, the change in CDS scores at T1 and T2 showed a significantly higher improvement in the bilateral simulation group than in two other groups (p < 0.05). There was a significantly larger change in the DOSS, PAS, and VDS scores at T1 in the bilateral stimulation group than in two other groups (p < 0.05). CONCLUSIONS: The results of the present study provide substantial evidence that 10 Hz rTMS at the bilateral motor cortices over the cortical areas projecting to the mylohyoid muscles is effective as an additional treatment strategy to traditional dysphagia therapies.

Prediction of Motor Recovery Using Quantitative Parameters of Motor Evoked Potential in Patients With Stroke.

OBJECTIVE: To investigate the clinical significance of quantitative parameters in transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP) which can be adopted to predict functional recovery of the upper limb in stroke patients in the early subacute phase. METHODS: One hundred thirteen patients (61 men, 52 women; mean age 57.8±12.2 years) who suffered faiarst-ever stroke were included in this study. All participants underwent TMS-induced MEP session to assess the corticospinal excitability of both hand motor cortices within 3 weeks after stroke onset. After the resting motor threshold (rMT) was assessed, five sweeps of MEP were performed, and the mean amplitude of the MEP was measured. Latency of MEP, volume of the MEP output curve, recruitment ratios, and intracortical inhibition and facilitation were also measured. Motor function was assessed using the Fugl-Meyer Assessment scale (FMA) within 3 weeks and at 3 months after stroke onset. Correlation analysis was performed between TMS-induced MEP derived measures and FMA scores. RESULTS: In the MEP response group, rMT and rMT ratio measures within 3 weeks after stroke onset showed a significant negative correlation with the total and upper limb FMA scores at 3 months after stroke (p<0.001). Multiple regression analysis revealed that FMA score and rMT ratio, but not rMT within 3 weeks were independent prognostic factors for FMA scores at 3 months after stroke. CONCLUSION: These results indicated that the quantitative parameter of TMS-induced MEP, especially rMT ratio in the early subacute phase, could be used as a parameter to predict motor function in patients with stroke.

Effect of cumulative repetitive transcranial magnetic stimulation on freezing of gait in patients with atypical Parkinsonism: A pilot study.

OBJECTIVE: To investigate the potential of cumulative high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on freezing of gait in atypical Parkinsonism. DESIGN: Randomized, single-blinded, crossover study with a blinded observer. PARTICIPANTS: Eight patients with atypical Parkinsonism. METHODS: All participants received HF-rTMS over the lower leg primary motor cortex (M1-LL) for 5 consecutive days. Alternative sham stimulation was also administered with a 2-week wash-out period. Freezing of Gait Questionnaire (FOG-Q), turn steps in the modified Standing Start 180° Turn Test, the Timed Up and Go (TUG) task, and the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) were performed before, after, and one week after rTMS. RESULTS: All participants completed this study without any significant adverse effects. FOG-Q and turn steps revealed significant improvements over time in the rTMS compared with the sham stimulation (χ2=6.067, p=0.048 and χ2=9.083, p=0.011). In addition, the TUG task and UPDRS-III showed significant improvements over time in the rTMS compared with the sham stimulation (χ2=7.200, p=0.02 and χ2=7.000, p=0.030). CONCLUSION: Cumulative HF-rTMS over the M1-LL might be effective for improving freezing of gait in patients with atypical Parkinsonism. Further investigation with a large number of participants is needed to clarify the effects of HF- rTMS on freezing of gait in atypical Parkinsonism.

Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.

BACKGROUND: Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment. METHODS: This phase IV trial was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 70 patients (Cerebrolysin n = 35, placebo n = 35) with moderate to severe motor function impairment were included within 7 days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo, given in addition to standardized rehabilitation therapy. Assessments were performed at baseline, immediately after treatment as well as 2 and 3 months after stroke onset. The plasticity of motor system was assessed by diffusion tensor imaging and with resting state functional magnetic resonance imaging. RESULTS: Both groups demonstrated significant improvement in motor function (p < 0.05); however, no significant difference was found between the two groups. In the stroke patients with severe motor impairment, the Cerebrolysin group exhibited significantly more improvement in motor function compared with the placebo group (p < 0.05). Effects of Cerebrolysin were demonstrated as restricted increments of corticospinal diffusivity and as recovery of the sensorimotor connectivity. CONCLUSION: The combination of standard rehabilitation therapy with Cerebrolysin treatment in the subacute stroke has shown additional benefit on motor recovery and plastic changes of the corticospinal tract in patients with severe motor impairment. TRIAL REGISTRATION: NCT01996761 (November 5, 2013).