Effects of DLPFC tDCS Followed by Treadmill Training on Dual-Task Gait and Cortical Excitability in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Gait disturbances are exacerbated in people with Parkinson's disease (PD) during dual-task walking (DTW). Transcranial direct current stimulation (tDCS) has been shown to exert beneficial effects on gait performance and cortical excitability in PD; however, its combined effects with treadmill training (TT) remain undetermined. OBJECTIVE: To investigate the effects of tDCS followed by TT on DTW performance and cortical excitability in individuals with PD. METHODS: Thirty-four PD participants were randomized to dorsal lateral prefrontal cortex (DLPFC) tDCS and TT group (DLPFC tDCS + TT group) or sham tDCS and TT group (sham tDCS + TT group) for 50 minutes per session (20 minutes tDCS followed by 30 minutes TT), 12 sessions within 5 weeks (2-3 sessions each week). Outcome measures included cognitive dual-task walking (CDTW), motor dual-task walking (MDTW), usual walking performance, cortical excitability, functional mobility, cognitive function, and quality of life. RESULTS: The DLPFC tDCS + TT group exerted significantly greater improvement in CDTW velocity (P = .046), cadence (P = .043), and stride time (P = .041) compared to sham tDCS + TT group. In addition, DLPFC tDCS + TT group demonstrated a significant increase in resting motor threshold of stimulated hemisphere compared with sham tDCS + TT group (P = .026). However, no significant differences between groups were found in MDTW performance and other outcomes. CONCLUSION: Twelve-session DLPFC tDCS followed by TT significantly improved CDTW performance and decreased cortical excitability more than TT alone in individuals with PD. Applying DLPFC tDCS prior to TT could be suggested for gait rehabilitation in individuals with PD. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12622000101785.

Effects of motor and cognitive complex training on obstacle walking and brain activity in people with Parkinson's disease: a randomized controlled trial.

BACKGROUND: The difficulties in obstacle walking are significant in people with Parkinson's disease (PD) leading to an increased fall risk. Effective interventions to improve obstacle walking with possible training-related neuroplasticity changes are needed. We developed two different exercise programs, complex walking training and motor-cognitive training, both challenging motor and cognitive function for people with PD to improve obstacle walking. AIM: To investigate the effects of these two novel training programs on obstacle walking and brain activities in PD. DESIGN: A single-center randomized, single-blind controlled study. SETTING: University laboratory; outpatient. POPULATION: Individuals with idiopathic PD. METHODS: Thirty-two participants were randomly assigned to the complex walking training group (N.=11), motor-cognitive training group (N.=11) or control group (N.=10). Participants in training groups received exercises for 40 minutes/session, with a total of 12-session over 6 weeks. Control group did not receive additional training. Primary outcomes included obstacle walking, and brain activities (prefrontal cortex (PFC), premotor cortex (PMC), and supplementary motor area (SMA)) during obstacle walking by using functional near-infrared spectroscopy. Secondary outcomes included obstacle crossing, timed up and go test (TUG), cognitive function in different domains, and fall efficacy scale (FES-I). RESULTS: The motor-cognitive training group demonstrated greater improvements in obstacle walking speed and stride length, SMA activity, obstacle crossing velocity and stride length, digit span test, and TUG than the control group. The complex walking training did not show significant improvement in obstacle walking or change in brain activation compared with control group. However, the complex walking training resulted in greater improvements in Rey-Osterrieth Complex Figure test, TUG and FES-I compared with the control group. CONCLUSIONS: Our 12-session of the cognitive-motor training improved obstacle walking performance with increased SMA activities in people with PD. However, the complex walking training did not lead such beneficial effects as the cognitive-motor training. CLINICAL REHABILITATION IMPACT: The cognitive-motor training is suggested as an effective rehabilitation program to improve obstacle walking ability in individuals with PD.

Effects of Transcranial Direct Current Stimulation Followed by Treadmill Training on Dual-Task Walking and Cortical Activity in Chronic Stroke: A Double-Blinded Randomized Controlled Trial.

OBJECTIVE: To explore the effects of transcranial direct current stimulation followed by treadmill training on dual-task gait performance and contralesional cortical activity in chronic stroke patients. METHODS: Forty-five chronic stroke participants were randomized into 3 groups: a bilateral transcranial direct current stimulation and treadmill training group; a cathodal transcranial direct current stimulation and treadmill training group; and a sham transcranial direct current stimulation and treadmill training group for 50 min per session (20 min transcranial direct current stimulation followed by 30 min treadmill training), 3 sessions per week for 4 weeks. Outcome measures included cognitive dual-task walking, motor dual-task walking, walking performance, contralesional cortical activity, and lower-extremity motor control. RESULTS: The cathodal transcranial direct current stimulation + treadmill training group showed significantly greater improvements in cognitive dual-task walking speed than the other groups (p cathodal vs sham = 0.006, p cathodal vs bilateral = 0.016). In the cathodal transcranial direct current stimulation + treadmill training group the silent period duration increased significantly more than in the other groups (p < 0.05). Changes in motor evoked potentials in the cathodal transcranial direct current stimulation + treadmill training group were greater than those in the sham transcranial direct current stimulation + treadmill training group (p < 0.05). No significant changes were observed in the bilateral transcranial direct current stimulation + treadmill training group. CONCLUSION: Cathodal transcranial direct current stimulation followed by treadmill training is an effective intervention for improving cognitive dual-task walking and modulating contralesional cortical activity in chronic stroke. No beneficial effects were observed after bilateral transcranial direct current stimulation and treadmill training.

Effects of Dual Task Training on Dual Task Gait Performance and Cognitive Function in Individuals With Parkinson Disease: A Meta-analysis and Meta-regression.

OBJECTIVE: To explore the effects of dual task (DT) training on DT gait performance and cognitive function in individuals with Parkinson disease (PD) and to examine factors that might influence the effects of DT training. DATA SOURCES: PubMed, Wiley Online Library, Cochrane Library, CINAHL, and Medline were searched for articles published from January 2006 to December 2021. STUDY SELECTION: Randomized controlled trials comparing DT training with usual care or general exercise were included. DATA EXTRACTION: The outcomes studied were DT gait parameters including speed, step and stride length, cadence, step and stride time variability, dual-task cost on gait speed, and Trail Making Tests presented as standardized mean differences (SMDs). The Grading of Recommendations, Assessment, Development, and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Ten randomized controlled trials with 466 participants were included in the meta-analysis. The included studies presented, in general, with a low to high risk of bias. Meta-analyses used a random-effects model for all analyses. The meta-analysis showed the DT training effects on DT gait speed (SMD=0.825, P=.012), DT step and stride length (SMD=0.400, P=.015), Trail Making Tests-part A (TMT-A; SMD=0.533, P=.010), and Trail Making Tests-part B (SMD=0.516, P=.012) compared with the control group. Only the effect on TMT-A was maintained at the follow-up assessment. The results of meta-regression showed that participants with slower initial single task gait speed improved more after DT training on DT step and stride length. CONCLUSIONS: The DT training improved more in DT gait speed with moderate-quality evidence as compared with usual care or conventional physical training in individuals with PD. The beneficial effects of DT training on DT step and stride length, attention, and executive function were also demonstrated in this meta-analysis. Furthermore, the improvement in the DT walking step and stride length was related to the participant's initial single task gait speed.

Comparing different montages of transcranial direct current stimulation on dual-task walking and cortical activity in chronic stroke: double-blinded randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation to modulate cortical activity for improving motor function. However, the different tDCS applications for modulating cortical activity and dual task gait performance in chronic stroke have not yet been investigated. This study investigated the effects of different tDCS applications on dual task gait performance and contralesional M1 activation in chronic stroke. METHODS: Forty-eight participants were randomized to anodal, bilateral, cathodal, and sham tDCS groups. Each group received 20 min of tDCS stimulation, except the sham group. Gait performance was measured by GaitRite system during cognitive dual task (CDT) walking, motor dual task (MDT) walking, and single walking (SW). Contralesional M1 activity of unaffected tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). Intragroup difference was analyzed by Wilconxon sign ranks test with Bonferroni correction, and Kruskal-Wallis one-way analysis of variance by ranks was used for intergroup comparisons, followed by post-hoc Mann-Whitney U tests with Bonferroni correction. RESULTS: The bilateral tDCS (p = 0.017) and cathodal tDCS (p = 0.010) improved the CDT walking speed more than sham group. The bilateral tDCS (p = 0.048) and cathodal tDCS (p = 0.048) also improved the MDT walking speed more than sham group. Furthermore, bilateral tDCS (p = 0.012) and cathodal tDCS (p = 0.040) increased the silent period (SP) more than the anodal and sham group. Thus, one-session of bilateral and cathodal tDCS improved dual task walking performance paralleled with increasing contralesional corticomotor inhibition in chronic stroke. CONCLUSIONS: Our results indicate that one-session of bilateral and cathodal tDCS increased contralesional corticomotor inhibition and improved dual task gait performance in chronic stroke. TRIAL REGISTRATION: Thai Clinical Trials Registry (TCTR20180116001). Registered prospectively on 16th Jan, 2018 at http://www.thaiclinicaltrials.org .

Transcranial Direct Current Stimulation on Different Targets to Modulate Cortical Activity and Dual-Task Walking in Individuals With Parkinson's Disease: A Double Blinded Randomized Controlled Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation to modulate cortical activity for improving motor function. However, the information of tDCS stimulation on different brain regions for dual-task walking and cortical modulation in Parkinson's disease (PD) has not yet been compared. OBJECTIVE: The objective of this study was to investigate the effects of different tDCS targets on dual-task gait performance and cortical activity in patients with PD. METHODS: A total of 36 participants were randomly assigned to primary motor cortex (M1) tDCS, dorsal lateral prefrontal cortex (DLPFC) tDCS, cerebellum tDCS, or Sham tDCS group. Each group received 20 min of tDCS stimulation, except for the Sham group. Gait performance was measured by the GAITRite system during dual-task walking and single walking. Corticomotor activity of the tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). The functional mobility was assessed using the timed up and go (TUG) test. RESULTS: All participants showed no significant differences in baseline data. Following the one session of tDCS intervention, M1 (p = 0.048), DLPFC (p < 0.001), and cerebellum (p = 0.001) tDCS groups demonstrated significant improvements in dual-task gait speed compared with a pretest. The time × group interaction [F(3, 32) = 5.125, p = 0.005] was detected in dual-task walking speed. The post hoc Tukey's test showed that the differences in gait speed were between the Sham tDCS group and the DLPFC tDCS group (p = 0.03). Moreover, DLPFC tDCS also increased the silent period (SP) more than M1 tDCS (p = 0.006) and Sham tDCS (p = 0.002). CONCLUSION: The results indicate that DLPFC tDCS exerted the most beneficial effects on dual-task walking and cortical modulation in participants with PD. CLINICAL TRIAL REGISTRATION: [http://www.thaiclinicaltrials.org/show/TCTR20200909005], Thai Clinical Trials Registry [TCTR20200909005].

Tumor suppressor PAX6 functions as androgen receptor co-repressor to inhibit prostate cancer growth.

BACKGROUND: PAX6, a transcription factor, has currently been suggested to function as a tumor suppressor in glioblastoma and to act as an early differentiation marker for neuroendocrine cells. The androgen receptor (AR) plays a pivotal role in prostate cancer development and progression due to its transcriptional activity in regulating genes involved in cell growth, differentiation, and apoptosis. To determine the role of PAX6 in prostate cancer, we investigated whether PAX6 interacts with AR to affect prostate cancer development. METHODS: We used immunostaining, RT-PCR, and Western blotting assays to show the expression status of PAX6 in prostate tissue and human prostate cancer cell lines. The role of PAX6 in cell growth and colony regeneration potential of LNCaP cells were evaluated by MTT assay and soft agar assay with PAX6-overexpressed LNCaP cells. Mammalian two-hybrid and co-immunoprecipitation (Co-IP) assays were used to demonstrate the interaction between PAX6 and AR. Reporter gene and Q-RT-PCR assays were performed to determine the effects of PAX6 on the function of AR. RESULTS: In prostate cancer tissues, PAX6 expression was stronger in normal epithelial cells than cancer cells, and decreased in LNCaP cells compared to that of DU145 and PC3 cells. Enforced expression of PAX6 suppressed the cell growth of LNCaP cells and also inhibited the colony formation of LNCaP cells. PAX 6 interacted with AR and repressed its transcriptional activity. PAX6 overexpression decreased the expression of androgen target gene PSA in LNCaP cells. CONCLUSIONS: In this study, we found that PAX6 may act as a prostate cancer repressor by interacting with AR and repressing the transcriptional activity and target gene expression of AR to regulate cell growth and regeneration.

Alternative splicing of the ovine CFTR gene.

Alternative splicing of the human CFTR gene was studied previously and shown not to generate functional CFTR-like chloride ion channels. However, it is possible that some of the alternatively spliced forms may encode CFTR proteins with different functions. The ovine CFTR gene is very similar to the human gene and has regulatory mechanisms in common. To evaluate whether the alternatively spliced forms of human CFTR are conserved in the sheep, the splice forms of the ovine CFTR gene were examined. A transcript lacking exon 9 was observed in the sheep, but unlike the human exon 9-transcript, it did not result from a polymorphic intron 8 splice acceptor site. Sheep CFTR transcripts lacking exon 17b were seen and have also been described in the human. Transcripts lacking 98 bp of the 5' end of exon 13, the whole of exon 13, and both exons 14b and 15 respectively were seen in sheep but have not been reported in human. Splice site donor and acceptor sequences were isolated, and alternative transcripts were shown to result from a combination of aberrant sites and competition of 5' splice donor sequences.