Attentional state-synchronous peripheral electrical stimulation during action observation induced distinct modulation of corticospinal plasticity after stroke.

Introduction: Brain computer interface-based action observation (BCI-AO) is a promising technique in detecting the user's cortical state of visual attention and providing feedback to assist rehabilitation. Peripheral nerve electrical stimulation (PES) is a conventional method used to enhance outcomes in upper extremity function by increasing activation in the motor cortex. In this study, we examined the effects of different pairings of peripheral nerve electrical stimulation (PES) during BCI-AO tasks and their impact on corticospinal plasticity. Materials and methods: Our innovative BCI-AO interventions decoded user's attentive watching during task completion. This process involved providing rewarding visual cues while simultaneously activating afferent pathways through PES. Fifteen stroke patients were included in the analysis. All patients underwent a 15 min BCI-AO program under four different experimental conditions: BCI-AO without PES, BCI-AO with continuous PES, BCI-AO with triggered PES, and BCI-AO with reverse PES application. PES was applied at the ulnar nerve of the wrist at an intensity equivalent to 120% of the sensory threshold and a frequency of 50 Hz. The experiment was conducted randomly at least 3 days apart. To assess corticospinal and peripheral nerve excitability, we compared pre and post-task (post 0, post 20 min) parameters of motor evoked potential and F waves under the four conditions in the muscle of the affected hand. Results: The findings indicated that corticospinal excitability in the affected hemisphere was higher when PES was synchronously applied with AO training, using BCI during a state of attentive watching. In contrast, there was no effect on corticospinal activation when PES was applied continuously or in the reverse manner. This paradigm promoted corticospinal plasticity for up to 20 min after task completion. Importantly, the effect was more evident in patients over 65 years of age. Conclusion: The results showed that task-driven corticospinal plasticity was higher when PES was applied synchronously with a highly attentive brain state during the action observation task, compared to continuous or asynchronous application. This study provides insight into how optimized BCI technologies dependent on brain state used in conjunction with other rehabilitation training could enhance treatment-induced neural plasticity.

Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.

Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process is demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nanostar loaded with triamcinolone is conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nanostar significantly elevates the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, is downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell is inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nanostar (Edu-MSCs-AuS-TA) promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain, improve general locomotor activity, and more importantly, induce cartilage regeneration even for severe stages of arthritis model.

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis.

Purpose: Rheumatoid arthritis (RA) is a highly prevalent form of autoimmune disease that affects nearly 1% of the global population by causing severe cartilage damage and inflammation. Despite its prevalence, previous efforts to prevent the perpetuation of RA have been hampered by therapeutics' cytotoxicity and poor delivery to target cells. The present study exploited drug repositioning and nanotechnology to convert metformin, a widely used antidiabetic agent, into an anti-rheumatoid arthritis drug by designing poly(lactic-co-glycolic acid) (PLGA)-based spheres. Moreover, this study also explored the thermal responsiveness of the IL-22 receptor, a key regulator of Th-17, to incorporate photothermal therapy (PTT) into the nanodrug treatment. Materials and Methods: PLGA nanoparticles were synthesized using the solvent evaporation method, and metformin and indocyanine green (ICG) were encapsulated in PLGA in a dropwise manner. The nanodrug's in vitro anti-inflammatory properties were examined in J744 and FLS via real-time PCR. PTT was induced by an 808 nm near-infrared (NIR) laser, and the anti-RA effects of the nanodrug with PTT were evaluated in DBA/1 collagen-induced arthritis (CIA) mice models. Further evaluation of anti-RA properties was carried out using flow cytometry, immunofluorescence analysis, and immunohistochemical analysis. Results: The encapsulation of metformin into PLGA allowed the nanodrug to enter the target cells via macropinocytosis and clathrin-mediated endocytosis. Metformin-encapsulated PLGA (PLGA-MET) demonstrated promising anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), increasing the expression of anti-inflammatory cytokines (IL-10 and IL-4), and promoting the polarization of M1 to M2 macrophages in J774 cells. The treatment of the nanodrug with PTT exhibited more potent anti-inflammatory effects than free metformin or PLGA-MET in CIA mice models. Conclusion: These results demonstrated that PLGA-encapsulated metformin treatment with PTT can effectively ameliorate inflammation in a spatiotemporal manner.

Attentional State-Dependent Peripheral Electrical Stimulation During Action Observation Enhances Cortical Activations in Stroke Patients.

Brain-computer interface (BCI) is a promising technique that enables patients' interaction with computers or machines by analyzing specific brain signal patterns and provides patients with brain state-dependent feedback to assist in their rehabilitation. Action observation (AO) and peripheral electrical stimulation (PES) are conventional methods used to enhance rehabilitation outcomes by promoting neural plasticity. In this study, we assessed the effects of attentional state-dependent feedback in the combined application of BCI-AO with PES on sensorimotor cortical activation in patients after stroke. Our approach involved showing the participants a video with repetitive grasping actions under four different tasks. A mu band suppression (8-13 Hz) corresponding to each task was computed. A topographical representation showed that mu suppression of the dominant (healthy) and affected hemispheres (stroke) gradually became prominent during the tasks. There were significant differences in mu suppression in the affected motor and frontal cortices of the stroke patients. The involvement of both frontal and motor cortices became prominent in the BCI-AO+triggered PES task, in which feedback was given to the patients according to their attentive watching. Our findings suggest that synchronous stimulation according to patient attention is important for neurorehabilitation of stroke patients, which can be achieved with the combination of BCI-AO feedback with PES. BCI-AO feedback combined with PES could be effective in facilitating sensorimotor cortical activation in the affected hemispheres of stroke patients.

Brain-computer interface-based action observation combined with peripheral electrical stimulation enhances corticospinal excitability in healthy subjects and stroke patients.

Objective.Action observation (AO) combined with brain-computer interface (BCI) technology enhances cortical activation. Peripheral electrical stimulation (PES) increases corticospinal excitability, thereby activating brain plasticity. To maximize motor recovery, we assessed the effects of BCI-AO combined with PES on corticospinal plasticity.Approach.Seventeen patients with chronic hemiplegic stroke and 17 healthy subjects were recruited. The participants watched a video of repetitive grasping actions with four different tasks for 15 min: (A) AO alone; (B) AO + PES; (C) BCI-AO + continuous PES; and (D) BCI-AO + triggered PES. PES was applied at the ulnar nerve of the wrist. The tasks were performed in a random order at least three days apart. We assessed the latency and amplitude of motor evoked potentials (MEPs). We examined changes in MEP parameters pre-and post-exercise across the four tasks in the first dorsal interosseous muscle of the dominant hand (healthy subjects) and affected hand (stroke patients).Main results.The decrease in MEP latency and increase in MEP amplitude after the four tasks were significant in both groups. The increase in MEP amplitude was sustained for 20 min after tasks B, C, and D in both groups. The increase in MEP amplitude was significant between tasks A vs. B, B vs. C, and C vs. D. The estimated mean difference in MEP amplitude post-exercise was the highest for A and D in both groups.Significance.The results indicate that BCI-AO combined with PES is superior to AO alone or AO + PES for facilitating corticospinal plasticity in both healthy subjects and patients with stroke. Furthermore, this study supports the idea that synchronized activation of cortical and peripheral networks can enhance neuroplasticity after stroke. We suggest that the BCI-AO paradigm and PES could provide a novel neurorehabilitation strategy for patients with stroke.

Vibration Perception Threshold and Related Factors for Balance Assessment in Patients with Type 2 Diabetes Mellitus.

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (DM). DPN causes a decrease in proprioception, which could reduce balance ability. We investigated the association of impaired vibration sense, based on vibration perception threshold (VPT), with assessments of balance and other factors affecting balance impairment and fear of falling in patients with type 2 DM. Sixty-three patients with DM aged >50 years were categorized as having normal vibration sense (NVS; n = 34) or impaired vibration sense (IVS; n = 29) according to a VPT value of 8.9 µm. The following parameters were evaluated for all patients: postural steadiness through the fall index using posturography, functional balance through the Berg Balance Scale (BBS), the Timed Up and Go test (TUG), and fear of falling through the Falls Efficacy Scale-International (FES-I). The IVS group showed a significantly greater balance impairment in fall index, BBS, and TUG, as well as greater fear of falling on the FES-I than the NVS group. The linear regression analysis showed that the fall index was associated only with the VPT, whereas BBS, TUG, and FES-I were associated with the VPT, age, and/or lower extremity muscle strength. VPT, age, and/or muscle strength were identified as predictors of balance and fear of falling in patients with type 2 DM. Therefore, along with age and lower extremity strength, the VPT can be useful for balance assessment in patients with type 2 DM.

Triamcinolone-Gold Nanoparticles Repolarize Synoviocytes and Macrophages in an Inflamed Synovium.

Understanding the crosstalk between synoviocytes and macrophages is very important for the development of strategies to regulate inflammatory responses in an inflamed synovium. Simultaneous regulation of the pro- and anti-inflammatory responses of synoviocytes and macrophages (repolarization) is critical for the treatment of arthritis. Thus, the immune regulatory functions of an ideal nanodrug should not only decrease the pro-inflammatory response but also effectively increase the anti-inflammatory response. In this study, crosstalk between synoviocytes and macrophages was found to be significantly involved in the activation and deactivation of inflammatory responses in the synovium. Interestingly, a developed triamcinolone-gold nanoparticle (Triam-AuNP) complex both decreased the pro-inflammatory responses and increased the anti-inflammatory responses of fibroblast-like synoviocytes (FLSs) and macrophages via repolarization of macrophages from the M1 to the M2 phenotype. In contrast, triamcinolone alone only decreased the pro-inflammatory responses of FLSs and macrophages without upregulating their anti-inflammatory responses. In vitro (human), ex vivo (human), and in vivo (mouse) analyses clearly indicated that Triam-AuNPs effectively regulated the expression of both pro- and anti-inflammatory cytokines in FLSs and effectively repolarized activity of macrophages in the inflamed synovium. Furthermore, Triam-AuNPs significantly promoted cartilage regeneration, whereas triamcinolone alone did not induce either FLS anti-inflammatory activity or macrophage repolarization.

Three-Dimensional Augmented Reality System for Balance and Mobility Rehabilitation in the Elderly: A Randomized Controlled Trial.

We attempted to evaluate the clinical efficiency of a novel three-dimensional interactive augmented reality system (3D-ARS) for balance and mobility rehabilitation. This system enables participant training with a realistic 3D interactive balance exercise and assessing movement parameters and joint angles by using a kinetic sensor system. We performed a randomized controlled trial in a general hospital. Thirty-six participants (age, 56-76 years) who could independently walk and stand on one leg were recruited. The participants were randomly assigned to either group. The control group (n = 18) underwent a conventional physical fitness program such as lower-extremity strengthening and balance training thrice per week for 1 month. The experimental group (n = 18) experienced 3D-ARS training thrice per week (1 session = 30 minutes) for 4 weeks. Training comprised a balloon game for hip exercise, cave game for knee exercise, and rhythm game for one-leg balance exercise. Lower-extremity clinical scale scores, fall index, and automatic balance score were measured by using Tetrax® posturography before, during, and after training. Significant group (3D-ARS vs. control) × time (before and after exercise) interaction effect was observed for Berg balance scale (BBS) scores (p = 0.04) and timed-up-and-go (TUG; p < 0.001). Overall improvements occurred in stability index, weight distribution index, fall risk index, and Fourier transformations index of posturography for both groups. However, score changes were significantly greater in the 3D-ARS group. Significant group × time interaction effect was observed for the fall risk index. This demonstrates that the 3D-ARS system can improve balance in the elderly more effectively.

Mobile Game Induces Active Engagement on Neuromuscular Electrical Stimulation Training in Patients with Stroke.

This study aimed to investigate the effectiveness of the mobile game-based neuromuscular electrical stimulation (MG-NMES) with assessing usability issues, such as attention and curiosity, and intrinsically interesting issues, which is necessary for successful poststroke rehabilitation. With the conventional NMES (C-NMES) system, the subjects underwent active repetitive cyclic NMES training. For assessment of usability issues, 20 hemiplegic stroke subjects were randomly divided into two groups. The subjects in the MG-NMES group (n = 9) and C-NMES group (n = 11) underwent 20 minutes of training each day for 5 days. We assessed the subjects' attention, curiosity, and intrinsically interesting issues; and using questionnaires they answered questions regarding their expectations of the training outcome after each training session. We found that the subjects in the MG-NMES group maintained their attention and interest for the 5 days, and their curiosity and expectation of a positive training outcome gradually increased as the training proceeded. In contrast, the C-NMES group reported no change in their attention or curiosity, but it was lower than the subjects in the MG-NMES group. In addition, their interest gradually decreased, which may have reduced their expectations of a positive outcome as the sessions progressed. There were no side effects during the training sessions in either group. The MG-NMES training paradigm developed is a new, readily available, and highly motivating MG-NMES training system. Based on the usability test, the reported advantages of the system were improved attention and flow experience during NMES training.

Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential.

Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or high-dose GC therapy can cause various serious adverse effects (adrenal insufficiency, hyperglycemia, Cushing's syndrome, osteoporosis, Charcot arthropathy, etc). In this study, developed DEX-carbon nanotube (CNT) conjugates improved intracellular drug delivery via increased caveolin-dependent endocytosis and ultimately suppressed the expression of major pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated human fibroblast-like synoviocytes (FLS) at low drug concentrations. Specifically, DEX on polyethylene-glycol (PEG)-coated CNTs induced caveolin uptake, recovered mitochondrial disruption, and inhibited reactive oxygen species production by targeting mitochondria that was released from the early endosome in TNF-α-stimulated FLS. The obtained results clearly demonstrated that DEX-PEG-coated CNTs significantly inhibited the inflammation by FLS in rheumatoid arthritis (RA) by achieving greater drug uptake and efficient intracellular drug release from the endosome, thus suggesting a mechanism of effective low-dose GC therapy to treat inflammatory diseases, including RA and osteoarthritis.

Virtual Reality-Guided Motor Imagery Increases Corticomotor Excitability in Healthy Volunteers and Stroke Patients.

OBJECTIVE: To investigate the effects of using motor imagery (MI) in combination with a virtual reality (VR) program on healthy volunteers and stroke patients. In addition, this study investigated whether task variability within the VR-guided MI programs would influence corticomotor excitability. METHODS: The present study included 15 stroke patients and 15 healthy right-handed volunteers who were presented with four different conditions in a random order: rest, MI alone, VR-guided MI, and VR-guided MI with task variability. The corticomotor excitability of each participant was assessed before, during, and after each condition by measuring changes in the various parameters of motor-evoked potentials (MEPs) of the extensor carpi radials (ECR). Changes in intracortical inhibition (ICI) and intracortical facilitation (ICF) were calculated after each condition as percentages of inhibition (%INH) and facilitation (%FAC) at rest. RESULTS: In both groups, the increases in MEP amplitudes were greater during the two VR-guided MI conditions than during MI alone. Additionally, the reductions in ECR %INH in both groups were greater under the condition involving VR-guided MI with task variability than under that involving VR-guided MI with regular interval. CONCLUSION: The corticomotor excitability elicited by MI using a VR avatar representation was greater than that elicited by MI with real body observations. Furthermore, the use of task variability in a VR program may enhance neural regeneration after stroke by reducing ICI. The present findings support the use of various VR programs as well as the concept of combining MI with VR programs for neurorehabilitation.

Effects of Radiation Therapy on Established Neurogenic Heterotopic Ossification.

Heterotopic ossification (HO) is frequently seen on rehabilitation units after spinal cord injuries, fractures, brain injuries, and limb amputations. Currently, there is no effective treatment for HO other than prophylaxis with anti-inflammatory medications, irradiation, and bisphosphonate administration. These prophylactic treatments are not effective for managing ectopic bone once it has formed. Here we describe three cases of established neurogenic HO treated with radiation therapy (RT). All patients had decreased serum alkaline phosphatase (ALP) and bone-specific ALP levels with decreased pain but increased range of motion immediately after RT. Post-treatment X-rays revealed no further growth of the HO. All patients maintained clinical and laboratory improvements 4 or 6 months after the RT. Our results suggest that RT is safe and effective in decreasing pain and activity of neurogenic HO.

Triamcinolone-carbon nanotube conjugation inhibits inflammation of human arthritis synovial fibroblasts.

Repetitive intra-articular corticosteroid injections are inevitable for treating synovial inflammation in advanced arthritis. However, short- and long-term use of corticosteroids usually triggers serious side effects (i.e., adrenal insufficiency, hyperglycemia, Cushing syndrome, osteoporosis, Charcot arthropathy, etc.). This study demonstrated that conjugation of a corticosteroid (triamcinolone) on polyethylene-glycol (PEG)-fabricated multi-walled carbon nanotubes enhances intracellular drug delivery via increased lysosome transport and ultimately suppresses the expression of major pro-inflammatory cytokines (i.e., TNF-α, IL-1ß, and IL-6) and matrix metalloproteinase-1 and -3 from fibroblast-like synoviocytes at a very low drug dose. Specifically, conjugation of triamcinolone and multi-walled carbon nanotubes inactivated nuclear factor-κB via inhibition of the phosphorylation of mitogen-activated protein kinases and the serine/threonine kinase Akt. In summary, low-dose triamcinolone conjugation with carbon nanotubes significantly inhibited the inflammatory response of fibroblast-like synoviocytes by achieving highly efficient intracellular trafficking and suggested a potential drug candidate for resolving side effects associated with conventional arthritis treatment.

Utility of a Three-Dimensional Interactive Augmented Reality Program for Balance and Mobility Rehabilitation in the Elderly: A Feasibility Study.

OBJECTIVE: To improve lower extremity function and balance in elderly persons, we developed a novel, three-dimensional interactive augmented reality system (3D ARS). In this feasibility study, we assessed clinical and kinematic improvements, user participation, and the side effects of our system. METHODS: Eighteen participants (age, 56-76 years) capable of walking independently and standing on one leg were recruited. The participants received 3D ARS training during 10 sessions (30-minute duration each) for 4 weeks. Berg Balance Scale (BBS) and the Timed Up and Go (TUG) scores were obtained before and after the exercises. Outcome performance variables, including response time and success rate, and kinematic variables, such as hip and knee joint angle, were evaluated after each session. RESULTS: Participants exhibited significant clinical improvements in lower extremity balance and mobility following the intervention, as shown by improved BBS and TUG scores (p<0.001). Consistent kinematic improvements in the maximum joint angles of the hip and knee were observed across sessions. Outcome performance variables, such as success rate and response time, improved gradually across sessions, for each exercise. The level of participant interest also increased across sessions (p<0.001). All participants completed the program without experiencing any adverse effects. CONCLUSION: Substantial clinical and kinematic improvements were observed after applying a novel 3D ARS training program, suggesting that this system can enhance lower extremity function and facilitate assessments of lower extremity kinematic capacity.

Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects.

BACKGROUND: There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training. METHODS: In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used. RESULTS: The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D). CONCLUSIONS: The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.

Development of virtual reality proprioceptive rehabilitation system for stroke patients.

In this study, the virtual reality (VR) proprioception rehabilitation system was developed for stroke patients to use proprioception feedback in upper limb rehabilitation by blocking visual feedback. To evaluate its therapeutic effect, 10 stroke patients (onset>3 month) trained proprioception feedback rehabilitation for one week and visual feedback rehabilitation for another week in random order. Proprioception functions were checked before, a week after, and at the end of training. The results show the click count, error distance and total error distance among proprioception evaluation factors were significantly reduced after proprioception feedback training compared to visual feedback training (respectively, p=0.005, p=0.001, and p=0.007). In addition, subjects were significantly improved in conventional behavioral tests after training. In conclusion, we showed the effectiveness and possible use of the VR to recover the proprioception of stroke patients.

Proprioception rehabilitation training system for stroke patients using virtual reality technology.

We investigated a virtual reality (VR) proprioceptive rehabilitation system that could manipulate the visual feedback of upper-limb during training and could do training by relying on proprioception feedback only. Virtual environments were designed in order to switch visual feedback on/off during upper-limb training. Two types of VR training tasks were designed for evaluating the effect of the proprioception focused training compared to the training with visual feedback. In order to evaluate the developed proprioception feedback virtual environment system, we recruited ten stroke patients (age: 54.7± 7.83years, on set: 3.29± 3.83 years). All patients performed three times PFVE task in order to check the improvement of proprioception function just before training session, after one week training, and after all training. In a comparison between FMS score and PFVE, the FMS score had a significant relationship with the error distance(r = -.662, n=10, p = .037) and total movement distance(r = -.726, n=10, p = .018) in PFVE. Comparing the training effect between in virtual environment with visual feedback and with proprioception, the click count, error distance and total error distance was more reduced in PFVE than VFVE. (Click count: p = 0.005, error distance: p = 0.001, total error distance: p = 0.007). It suggested that the proprioception feedback rather than visual feedback could be effective means to enhancing motor control during rehabilitation training. The developed VR system for rehabilitation has been verified in that stroke patients improved motor control after VR proprioception feedback training.

Development of a modified naturalistic action test for korean patients with impaired cognition.

OBJECTIVE: To develop and evaluate the psychometric properties of a modified Naturalistic Action Test (m-NAT) for Korean patients with impaired cognition. The NAT was originally designed to assess everyday action impairment associated with higher cortical dysfunction. METHODS: We developed the m-NAT by adapting the NAT for the Korean cultural background. The m-NAT was modeled as closely as possible on the original version in terms of rules and scoring. Thirty patients receiving neurorehabilitation (twenty-three stroke patients, five traumatic brain injury patients, and two dementia patients) and twenty healthy matched controls were included. Inter-rater reliability was assessed between two raters. Validity was evaluated by comparing the m-NAT score with various measures of attention, executive functions, and daily life. RESULTS: Performance on the m-NAT in terms of the total score was significantly different between patients and controls (p<0.01). Patients made significantly more total errors than controls (p<0.01). Omissions error was the most frequent type of error in patient group. Intraclass correlation coefficients for total m-NAT score was 0.95 (95% confidence interval [CI], 0.92 to 0.97; p<0.001); total error was 0.91 (95% CI, 0.89 to 0.92; p<0.001). Total m-NAT score showed moderate to strong correlations with Stroop test interference score & index, Trail Making Test parts A and B, Sustained Attention to Response Task commission error, Functional Independence Measure, Korean instrumental activities of daily living, Korean version of the Cognitive Failures Questionnaire, and Executive Behavior Scale (p<0.05). CONCLUSION: The m-NAT showed very good inter-rater reliability and adequate validity. The m-NAT adjusted to Korean cultural background can be useful in performance-based assessment of naturalistic action for clinical and research purposes.

Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy.

OBJECTIVE: To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN). METHODS: Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure. RESULTS: After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS. CONCLUSION: Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Upper extremity rehabilitation of stroke: facilitation of corticospinal excitability using virtual mirror paradigm.

BACKGROUND: Several experimental studies in stroke patients suggest that mirror therapy and various virtual reality programs facilitate motor rehabilitation. However, the underlying mechanisms for these therapeutic effects have not been previously described. OBJECTIVES: We attempted to delineate the changes in corticospinal excitability when individuals were asked to exercise their upper extremity using a real mirror and virtual mirror. Moreover, we attempted to delineate the role of visual modulation within the virtual environment that affected corticospinal excitability in healthy subjects and stroke patients. METHODS: A total of 18 healthy subjects and 18 hemiplegic patients were enrolled into the study. Motor evoked potential (MEP)s from transcranial magnetic stimulation were recorded in the flexor carpi radialis of the non-dominant or affected upper extremity using three different conditions: (A) relaxation; (B) real mirror; and (C) virtual mirror. Moreover, we compared the MEPs from the virtual mirror paradigm using continuous visual feedback or intermittent visual feedback. RESULTS: The rates of amplitude increment and latency decrement of MEPs in both groups were higher during the virtual mirror task than during the real mirror. In healthy subjects and stroke patients, the virtual mirror task with intermittent visual feedback significantly facilitated corticospinal excitability of MEPs compared with continuous visual feedback. CONCLUSION: Corticospinal excitability was facilitated to a greater extent in the virtual mirror paradigm than in the real mirror and in intermittent visual feedback than in the continuous visual feedback, in both groups. This provides neurophysiological evidence supporting the application of the virtual mirror paradigm using various visual modulation technologies to upper extremity rehabilitation in stroke patients.