Won Hyuk Chang

Longitudinal Changes of Resting-State Functional Connectivity During Motor Recovery After Stroke

Background and Purpose— Functional MRI (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in patients with stroke. Resting-state fMRI is applicable to patients with stroke who are not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in patients with stroke by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1). Methods— A longitudinal observational study using repeated fMRI experiments was conducted in 12 patients with stroke. Resting-state fMRI data were acquired 4 times over a period of 6 months. Patients participated in the first session of fMRI shortly after onset and thereafter in subsequent sessions at 1, 3, and 6 months after onset. Resting-state functional connectivity of the ipsilesional M1 was assessed and compared with that of healthy subjects. Results— Compared with healthy subjects, patients demonstrated higher functional connectivity with the ipsilesional frontal and parietal cortices, bilateral thalamus, and cerebellum. Instead, functional connectivity with the contralesional M1 and occipital cortex were decreased in patients with stroke. Functional connectivity between the ipsilesional and contralesional M1 showed the most asymmetry at 1 month after onset to the ipsilesional side. Functional connectivity of the ipsilesional M1 with the contralesional thalamus, supplementary motor area, and middle frontal gyrus at onset was positively correlated with motor recovery at 6 months after stroke. Conclusions— Resting-state fMRI elicited distinctive but comparable results with previous task-based fMRI, presenting complementary and practical values for use in the study of patients with stroke.

Robot-assisted Therapy in Stroke Rehabilitation

Research into rehabilitation robotics has grown rapidly and the number of therapeutic rehabilitation robots has expanded dramatically during the last two decades. Robotic rehabilitation therapy can deliver high-dosage and high-intensity training, making it useful for patients with motor disorders caused by stroke or spinal cord disease. Robotic devices used for motor rehabilitation include end-effector and exoskeleton types; herein, we review the clinical use of both types. One application of robot-assisted therapy is improvement of gait function in patients with stroke. Both end-effector and the exoskeleton devices have proven to be effective complements to conventional physiotherapy in patients with subacute stroke, but there is no clear evidence that robotic gait training is superior to conventional physiotherapy in patients with chronic stroke or when delivered alone. In another application, upper limb motor function training in patients recovering from stroke, robot-assisted therapy was comparable or superior to conventional therapy in patients with subacute stroke. With end-effector devices, the intensity of therapy was the most important determinant of upper limb motor recovery. However, there is insufficient evidence for the use of exoskeleton devices for upper limb motor function in patients with stroke. For rehabilitation of hand motor function, either end-effector and exoskeleton devices showed similar or additive effects relative to conventional therapy in patients with chronic stroke. The present evidence supports the use of robot-assisted therapy for improving motor function in stroke patients as an additional therapeutic intervention in combination with the conventional rehabilitation therapies. Nevertheless, there will be substantial opportunities for technical development in near future.

LoNG-TERM EFFECTS oF rTMS oN MoToR RECoVERY IN PATIENTS AFTER SuBACuTE STRoKE

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for treatment of stroke patients. However, most previous reports have described the short-term effects of rTMS on motor performance. We conducted a sham-controlled trial to evaluate long-term effects of high-frequency rTMS on motor recovery in subacute stroke patients. METHODS Twenty-eight patients were randomly divided into two groups, and received either real or control rTMS. Both treatments were accompanied by motor practice. A daily dose of 1000 pulses of subthreshold 10 Hz rTMS was applied over the primary motor cortex of the affected hemisphere for 10 days within one month after onset of stroke. Motor function was assessed before and after treatment, and 3 months after the stroke. RESULTS Motor function improved in both groups after treatment; however, patients who received real rTMS experienced additional improvement in motor function of the affected upper limb. Over 3 months after the stroke, the time and type of intervention for the Motoricity Index of the affected upper extremity showed significant interaction. CONCLUSION Positive long-term effects on motor recovery could be achieved after 10 daily sessions of high-frequency rTMS in conjunction with motor practice during the sub-acute period of stroke.

Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: Electric field simulation using individual MRI data

Transcranial direct current stimulation (tDCS) is a neuromodulation protocol that can facilitate or inhibit cortical excitability in particular areas of the brain. Although recent studies have reported that tDCS can successfully modulate the excitability of various brain sites, outcomes of tDCS were not consistent between subjects even when identical stimulation protocols were applied. Thus far, however, no studies have clearly verified the main cause of this individual variability. In this study, the main hypothesis was that individual variability in tDCS effects might be partly explained by anatomical differences among subjects. To verify our hypothesis, we investigated the relationship between the behavioral outcomes of a verbal working memory (WM) task and current density values at the dorsolateral prefrontal cortex (DLPFC) simulated using the finite element method (FEM). A 3-back verbal working memory task experiment was conducted in 17 healthy subjects before and after tDCS with cathode and anode electrodes located at the right supraorbital and F3 locations, respectively. The results showed that participants who showed evidence of enhanced WM task performance after tDCS had a significantly larger current density at the DLPFC than other participants, suggesting that inconsistent behavioral outcomes of tDCS might be partly due to individual anatomical differences.

Evaluation of local electric fields generated by transcranial direct current stimulation with an extracephalic reference electrode based on realistic 3D body modeling

In this study, local electric field distributions generated by transcranial direct current stimulation (tDCS) with an extracephalic reference electrode were evaluated to address extracephalic tDCS safety issues. To this aim, we generated a numerical model of an adult male human upper body and applied the 3D finite element method to electric current conduction analysis. In our simulations, the active electrode was placed over the left primary motor cortex (M1) and the reference electrode was placed at six different locations: over the right temporal lobe, on the right supraorbital region, on the right deltoid, on the left deltoid, under the chin, and on the right buccinator muscle. The maximum current density and electric field intensity values in the brainstem generated by the extracephalic reference electrodes were comparable to, or even less than, those generated by the cephalic reference electrodes. These results suggest that extracephalic reference electrodes do not lead to unwanted modulation of the brainstem cardio-respiratory and autonomic centers, as indicated by recent experimental studies. The volume energy density was concentrated at the neck area by the use of deltoid reference electrodes, but was still smaller than that around the active electrode locations. In addition, the distributions of elicited cortical electric fields demonstrated that the use of extracephalic reference electrodes might allow for the robust prediction of cortical modulations with little dependence on the reference electrode locations.

Effects of dual transcranial direct current stimulation on post-stroke unilateral visuospatial neglect

Based on the interhemispheric inhibition model of unilateral visuospatial neglect (USN) after stroke, the effects of dual-mode transcranial direct current stimulation (tDCS) over the parietal cortices were assessed in a double-blind random-order cross-over experiment. Ten chronic right hemispheric stroke patients (4 men; mean age: 62.6 years) with USN were recruited. All participants underwent three randomly arranged tDCS sessions: (1) dual-mode, anodal tDCS over the right posterior parietal cortex (PPC) and cathodal tDCS over the left PPC; (2) single-mode, anodal tDCS over the right PPC; and (3) sham mode. Each session lasted 20min. Before and immediately after the stimulation, a line bisection test and star cancelation test were carried out. In the line bisection test, significant improvements were observed after both the dual- and the single-mode tDCS (p<0.05), but not after sham stimulation. Statistical analysis showed a significant interaction between time and tDCS mode, where the dual tDCS had a stronger effect than the single or sham stimulation modes (p<0.05). The star cancelation test did not show any significant change. These results suggest that dual tDCS over the bilateral PPC is an effective method for the treatment of USN in stroke patients.

Transcranial direct current stimulation increases resting state interhemispheric connectivity

Transcranial direct current stimulation (tDCS) has been increasingly used to investigate human brain functions. Especially, tDCS on the dorsolateral prefrontal cortex (DLPFC) enhances cognitive functions in both healthy subjects and patients with neuropsychiatric disorders. In spite of its effects on behavioral improvement, neural correlates of tDCS on the DLPFC have not been fully described. In this study, we acquired resting state functional magnetic resonance imaging data before and after real or sham stimulation on the left DLPFC. Resting state functional connectivity of the stimulated brain region was compared between the two groups. Compared to the sham stimulation group, the tDCS group showed increased DLPFC connectivity to the right hemisphere and decreased DLPFC connectivity to the brain regions around the stimulation site in the left hemisphere. Application of tDCS on the DLPFC may induce increased interhemispheric connectivity even at rest, possibly associated with the behavioral effects of tDCS.

rTMS with motor training modulates cortico-basal ganglia-thalamocortical circuits in stroke patients.

BACKGROUND AND PURPOSE Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. METHODS Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. RESULTS Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p < 0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. CONCLUSION According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits.

Rapid analgesic onset of intra-articular hyaluronic acid with ketorolac in osteoarthritis of the knee.

OBJECTIVE The purpose of this study was to evaluate the efficacy of intra-articular ketorolac to improve intra-articular hyaluronic acid (HA) therapy in knee osteoarthritis with respect to the initiation of pain relief. METHODS This study was designed as a single-blind study with a blinded observer and a 3-month follow-up. Forty-three patients with knee osteoarthritis were randomized to the ketorolac group (n=21) or the HA group (n=22). Ketorolac group members were given three weekly intra-articular injections of HA with ketorolac and then two weekly intra-articular injections of HA; and HA group members were given five weekly intra-articular HA injections. Visual analog scale (VAS), pain rating score (PRS) and adverse events were assessed at baseline and at 1st, 3rd, 5th, and 16th week after treatment commencement. RESULTS Significant improvement regarding pain assessment tools was observed in the ketorolac group by the addition of ketorolac to HA as compared with the HA group within 16 weeks of follow-up (p < 0.05). In the ketorolac group, 5 of the 21 subjects developed focal post-injection knee pain for about 8 hours after injection. CONCLUSION Intra-articular HA with ketorolac showed more rapid analgesic onset than intra-articular HA alone and did not induce any serious complications.

Dynamic changes in the cortico-subcortical network during early motor learning.

BACKGROUND Failure of early motor learning due to damage in any brain area involved in this process may interfere with successful rehabilitation of such patients. OBJECTIVE We investigated the changes in activation of the motor network during sequential finger motor learning to delineate the characteristics of the cortico-subcortical network during motor skill learning. METHODS Twenty healthy, right-handed volunteers participated. Subjects were instructed to perform eight blocks of a sequential finger motor task while functional MRI (fMRI) was performed. RESULTS The participants had an improvement in performance over time from block 1 to block 4, indicating that successful learning had occurred, followed by a plateau from block 5 to the last block. On fMRI, activities of the contralateral primary sensorimotor cortex, the premotor cortex, the supplementary motor area, and the posterior parietal cortex gradually increased from block 1 to block 4 and then decreased from block 5 to the last. In contrast, activity of the ipsilateral cerebellum showed a linear increase spanning the last block with peak activation. The thalamus and basal ganglia showed unilateral or bilateral activities at the unique stage of motor learning. CONCLUSIONS These findings delineated the characteristic plastic changes and different roles of the cortico-subcortical network during the early phase of motor learning and automatization.