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Freezing of gait (FOG) is a debilitating gait disorder in people with Parkinson's disease (PD). While various neuroimaging techniques have been used to investigate the pathophysiology of FOG, changes in corticomotor excitability associated with FOG have yet to be determined. Research to date has not concluded if changes in corticomotor excitability are associated with gait disturbances in this patient population. This study aimed to use transcranial magnetic stimulation (TMS) to investigate corticomotor excitability changes associated with FOG. Furthermore, the relationship between corticomotor excitability and gait performances would be determined. Eighteen participants with PD and FOG (PD + FOG), 15 without FOG (PD - FOG), and 15 non-disabled adults (Control) were recruited for this study. Single and paired-pulse TMS paradigms were used to assess corticospinal and intracortical excitability, respectively. Gait performance was measured by the 10-Meter-Walk test. Correlation analysis was performed to evaluate relationships between TMS outcomes and gait parameters. Compared with the Control group, the PD + FOG group showed a significantly lower resting motor threshold and reduced short intracortical inhibition (SICI). Correlation analysis revealed a relationship between resting motor evoked potential and step length, and between SICI and walking velocity in the Control group. While the silent period correlated with step length in the PD - FOG group, no significant relationship was observed in the PD + FOG group. Compared to the Control group, the PD + FOG group exhibited reduced corticomotor inhibition. Distinct correlations observed among the three groups suggest that the function of the corticomotor system plays an important role in mediating walking ability in non-disabled adults and people with PD - FOG, while people with PD + FOG may rely on neural networks other than the corticomotor system to control gait.

Background Mirror therapy (MT) and augmented reality (AR) are gaining popularity in stroke rehabilitation. MT uses mirror visual feedback to promote bilateral brain coupling and increase primary motor cortex excitability. AR offers an interactive context of practice for promoting motor and cognitive recovery. MT and AR may complement each other for hybrid interventions in stroke rehabilitation. This study investigated the benefits of MT-primed AR (MT + AR) versus AR group, relative to conventional therapy (CT) for individuals with stroke. Method The study randomly assigned 45 stroke survivors to the MT + AR group, the AR, or the CT group, and 44 of them completed the experiment and were included in the analysis. Each treatment session was 90 min, 3 times a week, for 6 weeks. All assessments were administered before, immediately after treatment, and at 3 months. Primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Berg Balance Scale (BBS). Secondary outcome measures were the revised Nottingham Sensory Assessment (rNSA), Chedoke Arm and Hand Activity Inventory (CAHAI), Motor Activity Log (MAL), and Stroke Impact Scale Version 3.0 (SIS). Adverse events were monitored before and after each session. Results After 6 weeks of treatment, the three groups demonstrated significant improvements in the FMA-UE, BBS, CAHAI, MAL, and SIS. In the between-group comparisons, MT + AR and AR groups demonstrated significant advantages in the BBS, proprioception scale of rNSA and SIS, compared with the CT group. Only the MT + AR group, not the AR group, showed significantly better improvements in the FMA-UE and tactile scale of rNSA than the CT group. The MT + AR and AR alone showed differential benefits in the FMA-UE, tactile scale of rNSA, and SIS; the MT + AR rendered significantly better benefits. There were no significant differences among the three groups in the stereognosis scale of rNSA and MAL. No adverse effects were observed. Conclusion MT + AR and AR both effectively enhanced sensorimotor functions, balance and postural control, task performance, and life quality in patients with stroke with moderate-to-severe motor impairments. The results showed that MT + AR and AR were more beneficial for improving stroke survivors’ balance, functional mobility, proprioception recovery, and quality of life than the CT group. Furthermore, the MT + AR revealed better outcomes in the upper limb motor function and tactile sensory recovery. Between the MT + AR and AR comparisons, the MT + AR was more beneficial for improving upper limb motor function, tactile sensory recovery, and quality of life. Trial registration NCT05993091.

Background Combining robotic therapy (RT) with task-oriented therapy is an emerging strategy to facilitate motor relearning in stroke rehabilitation. This study protocol will compare novel rehabilitation regimens that use bilateral RT as a priming technique to augment two task-oriented therapies: mirror therapy (MT) and bilateral arm training (BAT) with a control intervention: RT combined with impairment-oriented training (IOT). Methods This single-blind, randomized, comparative efficacy study will involve 96 participants with chronic stroke. Participants will be randomized into bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT groups and receive 18 intervention sessions (90 min/day, 3 d/week for 6 weeks). The outcomes will include the Fugl-Meyer Assessment, Stroke Impact Scale version 3.0, Medical Research Council scale, Revised Nottingham Sensory Assessment, ABILHAND Questionnaire, and accelerometer and will be assessed at baseline, after treatment, and at the 3-month follow-up. Analysis of covariance and the chi-square automatic interaction detector method will be used to examine the comparative efficacy and predictors of outcome, respectively, after bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT. Discussion The findings are expected to contribute to the research and development of robotic devices, to update the evidence-based protocols in postacute stroke care programs, and to investigate the use of accelerometers for monitoring activity level in real-life situations, which may in turn promote home-based practice by the patients and their caregivers. Directions for further studies and empirical implications for clinical practice will be further discussed in upper-extremity rehabilitation after stroke. Trial registration This trial was registered December 12, 2018, at www.clinicaltrials.gov ( NCT03773653 ).

Degenerative cervical myelopathy (DCM) is a common aging condition caused by spinal cord compression. Individuals with DCM often presented with residual balance and functional impairments postoperatively. Perturbation-based balance training (PBT) has been shown to have positive effects on populations with neurological disorders but has yet to be investigated in DCM. The objective of this study was therefore to evaluate the effects of PBT on balance and functional performance in postoperative individuals with DCM. Fifteen postoperative individuals with DCM (DCM group) and 14 healthy adults (healthy control group) were recruited. The DCM group received a 4-weeks PBT using a perturbation treadmill. The outcome measures included mean velocity of center of pressure (COP) during quiet standing; center of mass (COM) variance and reaction time to balance perturbation during standing with forward and backward perturbation; gait speed during level ground walking; Timed Up and Go Test (TUG) and disability questionnaire scores including Visual Analog Scale, Neck Disability Index, and Lower Extremity Function of Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. The assessments were conducted pre- and post-training postoperatively for the DCM group but only once for the healthy control group. Significant improvements were observed in the mean velocity of COP, COM variance, reaction time, gait speed, and TUG in the DCM group. Disability questionnaire scores were not significantly different after training in DCM group. For between-group comparisons, significant differences that were observed pre-training were not observed post-training. The 4-weeks PBT is a potential rehabilitation strategy for addressing balance and functional impairment in postoperative individuals with DCM. In addition, the post-training performance in the DCM group exhibited trends comparable to those of age-matched healthy controls. Furthermore, the training regimens offer a practical reference for future studies on populations with balance disorders. Future studies complemented with neurophysiological assessments could reveal more information of the underlying mechanisms of PBT.

The priming effect of mirror visual feedback can be simply provided by inexpensive mirror therapy (MT), which exhibits beneficial effects on sensorimotor recovery in stroke. The present study was a single-blind pretest-posttest study that examined whether the priming effect of mirror visual feedback on bilateral task practice would render better outcomes. Twenty-three patients with chronic stroke were randomized to receive hospital-based task-oriented MT or bilateral arm training (BAT) for 4 weeks at 90 minutes/day, 3 days/week and a home practice for 30-40 minutes/day, 5 days/week. There was the potential trend for MT to improve temperature sense as measured by the revised Nottingham Sensory Assessment (Cohen’s d=1.00; 95% confidence interval, -0.09 to 2.09), and MT increased the Stroke Impact Scale 3.0 total score (d=0.89; 0.003 to 1.71). MT also showed a trend for greater improvements in the Motor Activity Log (amount of use: d=0.62; -0.24 to 1.44; quality of movement: d=0.50; -0.35 to 1.31). MT involving bilateral movement practice with the priming effect of mirror visual feedback may render beneficial effects. The unilateral approach or MT augmented by extra feedback might be appropriate modifications.

Organic fluorescent nanoparticles, excitation-dependent photoluminescence, hydrogen-bonded clusters and lysobisphosphatidic acid are four interesting individual topics in materials and biological sciences. They have attracted much attention not only because of their unique properties and important applications, but also because the nature of their intriguing phenomena remained unclear. Here we report a new type of organic fluorescent nanoparticles with intense blue and excitation-dependent visible fluorescence in the range of 410–620 nm. The nanoparticles are composed of ten bis(monoacylglycerol)bisphenol-A molecules and the self-assembly occurs only in elevated concentrations of 2-monoacylglycerol via radical-catalysed 3,2-acyl migration from 3-monoacylglycerol in neat conditions. The excitation-dependent fluorescence behaviour is caused by chromophores composed of hydrogen-bonded monoacylglycerol clusters, which are linked by an extensive hydrogen-bonding network between the ester carbonyl groups and the protons of the alcohols with collective proton motion and HO···C=O (n→π*) interactions. Organic fluorescent nanoparticles have potential biomaterials applications due to their low-toxicity and ‘green’ synthesis. Here, a series of self-assembled nanoparticles and polymers are synthesized with intense visible fluorescence stemming from chromophores of hydrogen-bonded monoacylglycerol clusters.

Background Robot-assisted therapy (RT) is a widely used intervention approach to enhance motor recovery in patients after stroke, but its effects on functional improvement remained uncertain. Neuromuscular electrical stimulation (NMES) is one potential adjuvant intervention approach to RT that could directly activate the stimulated muscles and improve functional use of the paretic hand. Methods This was a randomized, double-blind, sham-controlled study. Thirty-nine individuals with chronic stroke were randomly assigned to the RT combined with NMES (RT + ES) or to RT with sham stimulation (RT + Sham) groups. The participants completed the intervention 90 to 100 minutes/day, 5 days/week for 4 weeks. The outcome measures included the upper extremity Fugl-Meyer Assessment (UE-FMA), modified Ashworth scale (MAS), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and Stroke Impact Scale 3.0 (SIS). All outcome measures were assessed before and after intervention, and the UE-FMA, MAL, and SIS were reassessed at 3 months of follow-up. Results Compared with the RT + Sham group, the RT + ES group demonstrated greater improvements in wrist flexor MAS score, WMFT quality of movement, and the hand function domain of the SIS. For other outcome measures, both groups improved significantly after the interventions, but no group differences were found. Conclusion RT + ES induced significant benefits in reducing wrist flexor spasticity and in hand movement quality in patients with chronic stroke. Trial registration ClinicalTrials.gov. NCT01655446

Background Nonpharmacologic interventions, such as cognitive training or physical exercise, are effective in improving cognitive functions for older adults with mild cognitive impairment (MCI). Some researchers have proposed that combining physical exercise with cognitive training may augment the benefits of cognition. However, strong evidence is lacking regarding whether a combined therapy is superior to a single type of training for older adults with MCI. Moreover, which combination approach – combining physical exercise with cognitive training sequentially or simultaneously – is more advantageous for cognitive improvement is not yet clear. This proposed study is designed to clarify these questions. Methods/design This study is a single-blinded, multicenter, randomized controlled trial. Eighty individuals with MCI will be recruited and randomly assigned to cognitive training (COG), physical exercise training (PE), sequential training (SEQ), and dual-task training (DUAL) groups. The intervention programs will be 90 min/day, 2–3 days/week, for a total of 36 training sessions. The participants in the SEQ group will first perform 45 min of physical exercise followed by 45 min of cognitive training, whereas those in the DUAL group will perform physical exercise and cognitive training simultaneously. Participants will be assessed at baseline, after the intervention, and at 6-month follow-up. The primary cognitive outcome tests will include the Montreal Cognitive Assessment and the color-naming Stroop test. Other outcomes will include assessments that evaluate the cognitive, physical, and daily functions of older adults with MCI. Discussion The results of this proposed study will provide important information regarding the feasibility and intervention effects of combining physical exercise and cognitive training for older individuals with MCI. Trial registration ClinicalTrials.gov Identifier: NCT02512627 , registered on 20 July 2015.

ObjectiveTo observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies.MethodsA double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8.ResultsAt week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride.ConclusionThe combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.

In the first study, we recruited individuals with Parkinson's disease (PD), known to have striatum impairments, to test the hypothesis that striatum is a potential neural substrate for context-dependent learning. Ten individuals with PD and 10 age-matched non-disabled adults were recruited into the PD group and the Control group. The study was conducted over two consecutive days approximately 24 hours apart. On the first day, participants practiced a finger sequence task consisting of 3 numerical sequences. Unknown to the participants, each sequence was embedded within a specific colored circle and a specific location on the computer screen. On the second day, the participants were tested under two testing conditions: SWITCH and SAME conditions. Under the SWITCH condition, the context associated with each sequence was changed from that of practice; while under the SAME condition, the sequence-context association remained the same as practice. The primary outcome measure was total time accuracy cost (TTAC), which took both movement speed and accuracy into account. From the second day testing conditions, switch cost was calculated to indicate context-dependent learning. Switch cost was the TTAC performance difference between the SWITCH and SAME conditions normalized by the SAME condition (100 % × [SWITCH − SAME] / SAME). A larger switch cost value would indicate greater context-dependent learning. The results showed that individuals with PD and non-disabled adults demonstrated comparable learning of the finger sequence task when tested under the SAME condition. Study 2 was designed to investigate whether the frontostriatal circuit is associated with context-dependent learning. To indicate the integrity of the frontostriatal circuit, set-shifting ability was tested. The participants in Study 1 also participated in this study. After completion of the finger sequence task on the second day, the participants were given the trail making test (TMT) to assess their set-shifting ability. The result of the TMT was correlated with the TTAC switch cost obtained from Study 1. Findings from Study 2 showed that TTAC switch cost was positively correlated with the result of the TMT in people with PD, suggesting that an individual with PD who had greater difficulty performing set-shifting also demonstrated greater context-dependency. However, this relationship was not observed in non-disabled adults. The results of Study 2 suggested that context-dependent learning could be related to the integrity of the frontostriatal circuit. To test the hypothesis that the DLPFC plays a specific role in context-dependent learning, 30 non-disabled adults (age-matched to the participants with PD in Study 1) were recruited for Study 3. The participants were recruited into the Control group, the rTMS DLPFC group and rTMS Vertex group. The participants in the Control group were the same participants in Study 1. Similar to the procedures of Study 1, all participants practiced the finger sequence task on the first day. Before the SWITCH and SAME testing conditions on the second day, the participants in the rTMS DLPFC and rTMS Vertex groups received 1 Hz rTMS over the left DLPFC or the Vertex for 20 minutes. The rTMS DLPFC group demonstrated a reduced TTAC switch cost when compared to the Control group or the rTMS Vertex group, suggesting that perturbation to the DLPFC reduced context-dependent learning compared to the control conditions. Overall, findings from these three studies suggest that the neuronal interaction between the DLPFC and the striatum within the frontostriatal circuit have specific roles in context-dependent learning. While impairment of the striatum as exists in PD leads to a heightened context-dependent learning, decreased neuronal excitability of the DLPFC reduces context-dependency. Given these results, it is reasonable to hypothesize that the DLPFC is relatively over-activated in people with PD in order to compensate for the impaired striatum. This over-activation of the DLPFC with excessive encoding may be the cause of greater context-dependency observed in PD. (Abstract shortened by UMI.)