BackgroundFreezing of gait (FoG) is a severely disabling symptom in Parkinson’s disease (PD). The cortical mechanisms underlying FoG during locomotion tasks have rarely been investigated.ObjectivesWe aimed to compare the cerebral haemodynamic response during FoG-prone locomotion tasks in patients with PD and FoG (PD-FoG), patients with PD but without FoG (PD-nFoG), and healthy controls (HCs).MethodsTwelve PD-FoG patients, 10 PD-nFoG patients, and 12 HCs were included in the study. Locomotion tasks included normal stepping, normal turning and fast turning ranked as three difficulty levels based on kinematic requirements and probability of provoking FoG. During each task, we used functional near-infrared spectroscopy to capture concentration changes of oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB) that reflected cortical activation, and recorded task performance time. The cortical regions of interest (ROIs) were prefrontal cortex (PFC), supplementary motor area (SMA), premotor cortex (PMC), and sensorimotor cortex (SMC). Intra-cortical functional connectivity during each task was estimated based on correlation of ΔHBO2 between ROIs. Two-way multivariate ANOVA with task performance time as a covariate was conducted to investigate task and group effects on cerebral haemodynamic responses of ROIs. Z statistics of z-scored connectivity between ROIs were used to determine task and group effects on functional connectivity.ResultsPD-FoG patients spent a nearly significant longer time completing locomotion tasks than PD-nFoG patients. Compared with PD-nFoG patients, they showed weaker activation (less ΔHBO2) in the PFC and PMC. Compared with HCs, they had comparable ΔHBO2 in all ROIs but more negative ΔHHB in the SMC, whereas PD-nFoG showed SMA and PMC hyperactivity but more negative ΔHHB in the SMC. With increased task difficulty, ΔHBO2 increased in each ROI except in the PFC. Regarding functional connectivity during normal stepping, PD-FoG patients showed positive and strong PFC-PMC connectivity, in contrast to the negative PFC-PMC connectivity observed in HCs. They also had greater PFC-SMC connectivity than the other groups. However, they exhibited decreased SMA-SMC connectivity when task difficulty increased and had lower SMA-PMC connectivity than HCs during fast turning.ConclusionInsufficient compensatory cortical activation and depletion of functional connectivity during complex locomotion in PD-FoG patients could be potential mechanisms underlying FoG.Clinical trial registrationChinese clinical trial registry (URL: http://www.chictr.org.cn, registration number: ChiCTR2100042813).

BackgroundConstraint-induced movement therapy (CIMT) targeting the lower limb function uses various methods. The influence of CIMT methods on lower limb outcomes after stroke has rarely been examined.ObjectivesThis study aimed to examine CIMT effects on lower limb outcomes and explore the influence of CIMT methods on treatment effects after stroke, with other potential factors considered as covariates.MethodsPubMed, Web of Science, Cochrane Library, Academic Search Premier via EBSCOHost, and PEDro databases were searched until September 2022. We included randomized control trials with CIMT targeting the lower limb function and dosage-matched active control. The Cochrane risk-of-bias tool was used to evaluate the methodological quality of each study. Hedges' g was used to quantify the effect size of CIMT on outcomes compared to the active control. Meta-analyses were conducted across all studies. A mixed-variable meta-regression analysis was used to investigate the influence of CIMT methods on treatment effects after stroke, with other potential factors considered as covariates.ResultsTwelve eligible randomized controlled trials with CIMT were included in the meta-analysis, where 10 trials were with a low risk of bias. A total of 341 participants with stroke were involved. For the treatment effects on the lower limb function, CIMT showed a moderate short-term effect size [Hedges' g = 0.567; P > 0.05; 95% confidence interval (CI): 0.203–0.931], but a small and insignificant long-term effect size (Hedges' g = 0.470; P > 0.05; 95%CI: −0.173 to 1.112), compared with conventional treatment. The CIMT method of using a weight strapped around the non-paretic leg and the ICF outcome category of the movement function were identified as significant factors contributing to the heterogeneity of short-term effect sizes across studies (β = −0.854 and 1.064, respectively, R2 = 98%, P > 0.05). Additionally, using a weight strapped around the non-paretic leg had a significant contribution to the heterogeneity of long-term effect sizes across studies as well (β = −1.000, R2 = 77%, P > 0.05).ConclusionConstraint-induced movement therapy is superior to conventional treatment for improvement of lower limb function in the short-term but not in the long-term. The CIMT method of using a weight strapped around a non-paretic leg contributed negatively to the treatment effect, and therefore might not be recommended.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021268681.