Dae-Yul Kim

Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients.

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernickes area) or the right Wernickes area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernickes area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.

Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke.

Kim DY, Lim JY, Kang EK, You DS, Oh MK, Oh BM, Paik NJ: Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke. Objective: To test the hypothesis that 10 sessions of transcranial direct current stimulation combined with occupational therapy elicit more improvement in motor function of the paretic upper limb than sham stimulation in patients with subacute stroke. Design: Eighteen patients with subacute stroke with hand motor impairment were randomly assigned to one of the three 10-day sessions of (a) anodal transcranial direct current stimulation over the affected motor cortex, (b) cathodal transcranial direct current stimulation over the unaffected motor cortex, or (c) sham stimulation. Blinded evaluators assessed upper limb motor impairment and global functional state with the Fugl-Meyer Assessment score and the Modified Barthel Index at baseline, 1 day after stimulation, and 6 mos after stimulation. Results: Baseline scores for Fugl-Meyer Assessment and Modified Barthel Index were comparable in all groups (P > 0.05). At 6-mo follow-up, cathodal transcranial direct current stimulation led to a greater improvement in Fugl-Meyer Assessment than the sham procedure (P < 0.05). There was a significant inverse correlation between baseline Fugl-Meyer Assessment and Fugl-Meyer Assessment increase at 6 mos (r = −0.846; P < 0.01). Conclusions: Our results suggest a potentially beneficial effect of noninvasive cortical stimulation during rehabilitative motor training of patients who have suffered from subacute strokes.

Effect of high- and low-frequency repetitive transcranial magnetic stimulation on visuospatial neglect in patients with acute stroke: a double-blind, sham-controlled trial.

OBJECTIVE To compare the therapeutic effect of low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) in patients with acute stroke with visuospatial neglect. DESIGN This study was a prospective, double-blind, sham-controlled trial. Data are presented from 27 patients (15 men, 12 women; mean age, 67.0y) randomly assigned to receive 10 sessions of low-frequency (1Hz) rTMS over the nonlesioned PPC, high-frequency (10Hz) rTMS over the lesioned PPC, or sham stimulation. SETTING National university hospital. PARTICIPANTS Patients (N=27) diagnosed with visuospatial neglect after stroke. INTERVENTION Ten sessions of rTMS over a 2-week period. MAIN OUTCOME MEASURES The severity of visuospatial neglect was assessed pre- and posttreatment using the Motor-Free Visual Perception Test, line bisection test, star cancellation test, and Catherine Bergego Scale. RESULTS When comparing the differences in the Motor-Free Visual Perception Test, line bisection test, star cancellation test, Catherine Bergego Scale, and Korean-Modified Barthel Index (K-MBI) scores before and after treatment according to group, we found that changes in the line bisection test and K-MBI scores were significantly different between 3 groups. In the post hoc analysis, the improvement in the line bisection test score in the high-frequency rTMS group was statistically significant compared with that in the sham stimulation group (high vs sham P=.03, low vs sham P=.09, high vs low P=.58), and the improvements in the K-MBI scores of the 2 rTMS groups were statistically significant compared with those in the sham stimulation group (high vs sham P<.01, low vs sham P=.02, high vs low P=.75). CONCLUSIONS These results indicate that high-frequency rTMS is effective in the treatment of visuospatial neglect in patients with acute stroke.

Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1day vs. 1week after cerebral ischemia in rats

Transcranial direct current stimulation (tDCS) is an emerging tool for improving recovery from stroke. However, there has been no trial to determine whether it has a therapeutic benefit in the early stage of cerebral ischemia, and there is no consensus on the optimal time window of stimulation. Here, we described the effects of anodal tDCS in early cerebral ischemia, assessing functional improvements and changes in neuronal plasticity, and identifying the optimal time window for delivering tDCS to maximize functional gains. Thirty rats were randomly assigned to three groups: sham (n=10); early tDCS (ET), receiving tDCS 1day after ischemia for 5 days (n=10), and late tDCS (LT), receiving tDCS 1 week after ischemia for 5 days (n=10). Both ET and LT groups showed improved Barnes maze performance and motor behavioral index scores. However, only the LT group exhibited improvement in beam balance test. Immunohistochemical stainings showed that the ET group reinforced notable MAP-2 expression and the LT group enhanced mainly the level of GAP-43 in both peri-lesional and contralesional cortex. These immunohistochemical results had significant correlation with behavioral and cognitive functions. However, brain MRI and (1)H MRS showed no significant differences among the three groups in ischemic volume and metabolic alteration. These results suggest that anodal tDCS has the potential to modulate neural plasticity around the ischemic penumbra and even in the contralesional area without aggravating infarction volume and metabolic alteration. The degree of functional improvement was slightly greater when tDCS was applied 1 week rather than 1 day after ischemic injury.

RECOVERY OF SWALLOWING FUNCTION IS ACCOMPANIED BY THE EXPANSION OF THE CORTICAL MAP

To determine whether multiple sessions of electrical stimulation (ES) applied to neck muscles improve swallowing function and whether this improvement is accompanied by cortical reorganization in patients with dysphagia, before-after trials were performed on eight subjects. ES was applied for 1 hour, 5 days a week for 2 weeks. Swallowing function significantly improved after 2 weeks of ES, and this change was found to correlate with cortical reorganization measured by corticobulbar output maps. This study suggests that multiple sessions of ES applied to the neck muscles improve swallowing function via a mechanism involving long-term cortical reorganization.

Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: a pilot study.

OBJECTIVE To determine whether a single session of anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex improves attention in patients with traumatic brain injury. DESIGN Double-blinded, cross-over design. PATIENTS Nine patients with attention deficit after traumatic brain injury. METHODS Patients underwent a computerized contrast reaction time task before and after the administration of real transcranial direct current stimulation (2 mA for 20 min) or sham transcranial direct current stimulation (2 mA for 1 min) to the left dorsolateral prefrontal cortex in a double-blind, crossover manner. RESULTS Immediately post-stimulation, the transcranial direct current stimulation group showed a tendency of shortened reaction time relative to baseline (87.3 ± 7.8%), whereas the sham stimulation group (122.4 ± 715.5%) did not (p = 0.056). However, this difference was not significant 3 or 24 h after stimulation (p > 0.05). The numbers of correct responses were not changed at any time after stimulation. CONCLUSION Anodal transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex improves attention compared with sham stimulation in patients with traumatic brain injury, which suggests a potential role for this intervention in improving attention during cognitive training after traumatic brain injury. A further prospective randomized trial is required to confirm the benefits conferred by transcranial direct current stimulation in this patient population.

Effect of repetitive transcranial magnetic stimulation on cognition and mood in stroke patients: a double-blind, sham-controlled trial.

Kim BR, Kim DY, Chun MH, Yi JH, Kwon JS: Effect of repetitive transcranial magnetic stimulation on cognition and mood in stroke patients: A double-blind, sham-controlled trial. Objective:This study examined whether repetitive transcranial magnetic stimulation applied over the left dorsolateral prefrontal cortex (DLPFC) affected cognition or mood in poststroke patients. Design:The study was a single-center, prospective, double-blind, sham-controlled preliminary study. Eighteen patients (10 males and 8 females; average age, 62.9 yrs) were enrolled. All participants were randomly assigned to one of three treatment groups: low-frequency (1 Hz) stimulation, high-frequency (10 Hz) stimulation, and sham stimulation (control). Each patient underwent 10 consecutive treatment sessions (five times per week for 2 wks). A Computerized Neuropsychological Test was used to evaluate cognitive function, the Tower of London test was used to assess executive function, the Modified Barthel Index score was used to assess activity of daily living function, and the Beck Depression Inventory was used to assess mood status. These evaluations were conducted in all patients before and after treatment. Results:Treatment had no significant effect on any cognitive function parameter, including the Tower of London scores, in any of the three groups. In contrast, high-frequency repetitive transcranial magnetic stimulation resulted in significantly lower Beck Depression Inventory scores compared with baseline and compared with the other two groups. The Modified Barthel Index scores significantly increased in all three groups. Conclusions:These preliminary data suggest that there was a positive effect on mood, but the study was not powered to detect any measurable effect on cognition.

Mild to Moderate Early Exercise Promotes Recovery from Cerebral Ischemia in Rats

OBJECTIVE We examined the effects of various exercise intensities on recovery from middle cerebral artery occlusion (MCAO) in rats. METHODS First, we administered a 120-minute left MCAO to male Sprague-Dawley rats and randomly assigned them to one of four groups: no exercise (Group 1), mild exercise (Group 2), moderate exercise (Group 3), and severe exercise (Group 4). Then, we trained the rats for 30 min per day for one week or two weeks. We used a five-point neurological evaluation scale to measure neurological deficits 1-day, 4-days, 7-days, 10-days and 14-days after MCAO and measured infarct volume by use of 2% 2,3,4-triphenyltetrazolium chloride in exercised brains. We also performed immunohistochemistry analysis of the brain to observe reactive astrocytosis at the peri-infarct region. RESULTS Neurological examination indicated that Group 2 and 3 recovered better than Group 1 after one week and two weeks (p < 0.05). Moreover, Group 2 and 3 had reduced brain infarct volume compared with Group 1 after one week (p < 0.05). There were no significant differences between Group 4 and Group 1. The thickness of the peri-infarct astrocytosis was significantly reduced in Group 4 relative to Group 1 after one week. There was a significant negative correlation between the extent of reactive astrocytosis and neurological recovery (r = -0.648, p < 0.01). CONCLUSION This study demonstrates that mild to moderate exercise that begins soon after induced cerebral ischemia promotes recovery and that astrocytes may have an important role in the recovery process.

Effect of human embryonic stem cell-derived neuronal precursor cell transplantation into the cerebral infarct model of rat with exercise

We analyzed the therapeutic effect of the transplantation of the human embryonic stem cell (NIH Code: MB01)-derived neuronal precursor (hES-NP) cell and post-ischemic exercise in rats with the middle cerebral artery (MCA) infarct model. A cortical infarct was induced in 20 adult Sprague-Dawley rats by occlusion and reperfusion of the MCA. The rats were divided into four groups: hES-NP cell transplantation and exercise, transplantation only, exercise only, and Sham-operated with no exercise. In the cell-transplanted group, hES-NP cells were transplanted by stereotactic inoculation into the ipsilateral basal ganglia 7 days after infarct. We evaluated the clinical recovery of deficit, the size of infarct and the survival, migration, and differentiation of the transplanted cells. The transplanted hES-NP cells survived robustly in the ischemic brains 3 weeks post transplant. The majority of migrating cells in the ischemic rats had a neuronal phenotype. The clinical scores of all of the experimental groups were better than those of the Sham-operated group. Whereas the exercise-only group showed continuous clinical improvement, the cell-transplanted groups manifested less improvement than the exercise-only group. Moreover, the cell-transplanted groups did not differ in clinical improvement according to postinfarct-exercise or not. The infarct size was significantly reduced in both the cell-transplanted groups and the post-ischemic exercise group, compared with the Sham-operated group; however, the reduction of infarct size was most prominent in the exercise-only group. In our study, the inoculated site of the basal ganglia showed some damage induced by inoculation, such as loss of neuroglial cells, reactive gliosis and microcalcification, which was found in the Sham-operated group as well, and yet no inoculation-site injury has ever been reported. Our study revealed that stem cell transplantation can have a positive effect on behavioral recovery and reduction of infarct size, but the effect shown was no better than the effect of the exercise, which finding reconfirmed the importance of post-infarct rehabilitation. In addition, it was found that cell inoculation should be replaced by a noninvasive procedure.

CENTRAL EFFECT OF BOTULINUM TOXIN TYPE A IN HUMANS

This study investigated the changes in the cortical excitability with a paired-pulse transcranial magnetic stimulation (TMS) model after a botulinum toxin type A (BTA) injection in normal humans. Ten healthy subjects were enrolled in the study, which involved applying paired TMS to the motor cortex and recording the motor evoked potentials (MEP) before and after the BTA injection. BTA (2.5 mouse units) was injected into the right extensor digitorium brevis muscle. The amplitudes of MEP during rest and the cortical silent period (CSP) for the period of the tonic muscle contraction were measured at an interstimulus interval (ISI) of 3 ms and 20 ms. One month and three months after BTA injection, the level of intracortical inhibition increased significantly at an ISI of 3 ms and the intracortical facilitation decreased at an ISI of 20 ms. The duration of CSP shortened significantly at an ISI of 3 ms 1 month after BTA injection, which was also shortened significantly at an ISI of 20 ms. These findings were maintained until 3 months after the injection. It was concluded that cortical excitability could be modified by BTA injection in normal humans.