Greater prefrontal activation during sitting toe tapping predicts severer freezing of gait in Parkinson's disease: an fNIRS study.

OBJECTIVE: Previous studies have revealed that, compared with Parkinson's disease (PD) patients without freezing of gait (FoG), the ones with FoG showed greater prefrontal activation while doing lower-limb movements involving standing, walking and turning, which require both locomotor and balance control. However, the relation between FoG and pure locomotor control as well as its underlying mechanism remain unclear. METHODS: A total of 56 PD subjects were recruited and allocated to PD-FoG and PD-noFoG subgroups, and 34 age-matched heathy adults were included as heathy control (HC). Functional near-infrared spectroscopy was used to measure their prefrontal activation in a sitting lower-limb movement task, wherein subjects were asked to sit and tap their right toes as big and as fast as possible. RESULTS: Result of one-way ANOVA (Group: PD-FoG vs. PD-noFoG vs. HC) revealed greater activation in the right prefrontal cortex in the PD-FoG group than in the other 2 groups. Linear mixed-effects model showed consistent result. Furthermore, the right prefrontal activation positively correlated with the severity of FoG symptoms in PD-FoG patients. CONCLUSION: These findings suggested that PD patients with FoG require additional cognitive resources to compensate their damaged automaticity in locomotor control, which is more pronounced in severe FoG patients than milder ones.

Survival in patients with Parkinson's disease: a ten-year follow-up study in northern China.

BACKGROUND: A thorough understanding of the factors that influence patient survival in Parkinson's disease (PD) will aid in prognosis prediction and provide a new direction for disease modification treatment. Currently, there are no standardized mortality ratio (SMR) data for PD patients in the northern Chinese mainland. The main focus of this study was to determine which factors in the prospectively collected baseline characteristics can affect the survival of PD patients. In addition, for the first time, we investigated the SMR of PD patients in northern China. METHODS: Between 2009 and 2012, 218 PD patients were continuously recruited from the movement disorder clinic of the First Affiliated Hospital of Dalian Medical University and followed up until death or May 31, 2021. The prespecified prognostic variables were demographics, clinical features, lifestyle factors, and drug dose prospectively collected at baseline. To determine the independent predictors of survival during follow-up, the Cox proportional hazards model was used. Kaplan-Meier analysis was applied to estimate the overall survival curve and to compare survival between layers based on statistically significant predictors. The SMR of this northern Chinese mainland PD cohort was calculated. RESULTS: After a mean follow-up of 9.58 ± 2.27 years, 50 patients (22.90%) died. Factors that could individually predict shortened survival during follow-up included older age at onset (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.06-1.15), Hoehn and Yahr (H&Y) stage ≥ 3 (HR 9.36, 95% CI 2.82-31.03) and severe cognitive impairment (HR 6.18, 95% CI 2.75-13.88). Univariate Cox regression revealed that a certain amount of physical activity was associated with better survival (HR 0.41, 95% CI 0.22-0.74), while fatigue was associated with an increased risk of death (HR 2.54, 95% CI 1.37-4.70). The overall SMR was 1.32 (95% CI 0.98-1.74). CONCLUSIONS: Older age at onset, higher baseline H&Y stage, and severe cognitive impairment have a negative impact on survival. The 10-year survival of PD patients is not significantly different from that of the general population in China.

Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study.

INTRODUCTION: The use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. RESULTS: Compared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. CONCLUSION: These findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.

The impact of anxiety on the cognitive function of informal Parkinson's disease caregiver: Evidence from task-based and resting-state fNIRS.

Informal Parkinson's disease (PD) caregivers are considered to experience high levels of caregiver burden, negatively affecting the health of caregivers. However, few studies explored the relationship between anxiety in caregiver burden and cognitive function in informal PD caregivers. Although, no study has even investigated the neural mechanisms underlying this connection. This study aimed to conduct comprehensive cognitive and clinical assessments and evaluate brain activity from task-based state and resting-state using functional near-infrared spectroscopy (fNIRS). A total of ten informal PD caregivers and 15 matched, healthy, non-caregivers were recruited. Comprehensive cognitive and clinical assessments were conducted to evaluate five cognitive domains and mental states. Neural activity induced by verbal fluency task (VFT) and brain connectivity during resting state were monitored, and their correlations with the neuropsychological and clinical tests were explored. Our results showed that compared to non-caregiver, an informal PD caregiver exhibited no difference in most cognitive domains of function but performed better in attentional function, along with higher levels of anxiety. Decreased activation over prefrontal regions during VFT and hypo-connectivity within the frontoparietal network (FPN) and between default mode network (DMN) and FPN in the resting state were confirmed in this study as a result of the negative effects of anxiety on the brain. Furthermore, Spearman's correlation found that neural activity in FPN during task-based state and resting state was negatively correlated with the severity of anxiety. These findings indicate that despite normal or even better cognitive function, informal PD caregivers have impaired brain function, and this deficit in neural activity was related to anxiety.

Therapeutic benefits of music-based synchronous finger tapping in Parkinson's disease-an fNIRS study protocol for randomized controlled trial in Dalian, China.

BACKGROUND: Music therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson's disease, Alzheimer's disease, and major depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients. METHODS: For patients suffering from Parkinson's disease (PD), we propose a daily 25-min music-based synchronous finger tapping (SFT) intervention for 8 weeks. Eligible participants with PD are split into two groups: an intervention group and a control arm. In addition, a third cohort of healthy controls will be recruited. Assessment of finger tapping performances, the Unified Parkinson's Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) are measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups are compared to baseline performances from healthy controls. DISCUSSION: This exploratory prospective trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease. The study's findings are used to inform larger clinical studies for optimization and further exploration of the therapeutic effects of movement-based music therapy on neural activity in neurological diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04212897 . Registered on December 30, 2019. The participant recruitment and study protocol have received ethical approval from the First Affiliated Hospital of Dalian Medical University. The hospital Protocol Record number is PJ-KY-2019-123. The protocol was named "fNIRS Studies of Music Intervention of Parkinson's Disease." The current protocol is version 1.1, revised on September 1, 2020.