Ahee Lee

The brain-derived neurotrophic factor Val66Met polymorphism and degeneration of the corticospinal tract after stroke: a diffusion tensor imaging study

A common single nucleotide polymorphism, Val66Met, in the human brain‐derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long‐term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity.

What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS.

Prediction of Motor Recovery Using Diffusion Tensor Tractography in Supratentorial Stroke Patients With Severe Motor Involvement

Objective To investigate whether early stage diffusion tensor tractography (DTT) values predict motor function at 3 months after onset in supratentorial stroke patients with severe motor involvement. Methods A retrospective study design was used to analyze medical records and neuroimaging data of 49 supratentorial stroke patients with severe motor involvement. Diffusion tensor imaging was assessed within 3 weeks after stroke in all patients. Three-dimensional tractography of the ipsilateral corticospinal tract (CST) was performed using the fiber assignment of the continuous tracking algorithm. The two-step DTT analysis was used. The first step was classification according to ipsilateral CST visualization. The second step was a quantitative analysis of the visible-CST group parameters. Motor function was assessed at 2 weeks and at 3 months after stroke. Comparative and correlation analyses were performed between DTT-derived measures and motor assessment scores. Results Motor function of the upper extremity at 3 months after stroke was significantly higher in the visible-CST group than that in the nonvisible-CST group (p<0.05). Early stage fractional anisotropy was of DTT correlated significantly with upper extremity motor function at 3 months after stroke in the visible-CST group (p<0.05). Conclusion These results demonstrate that early DTT-derived measures predict motor recovery in the upper extremity at 3 months after onset in supratentorial stroke patients with severe motor involvement.

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.

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.

Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

Brain connectivity analysis has been widely used to investigate brain plasticity and recovery‐related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery‐related indicators according to initial severity.

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.

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.

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.

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.