The Postural Instability/Gait Difficulty (PIGD) subtype of Parkinson\'s disease (PD) has a faster disease progression, a higher risk of cognitive and motor decline, yet the alterations of structural topological organization remain unknown. Diffusion Tensor Imaging (DTI) and 3D-TI scanning were conducted on 31 PD patients with PIGD (PD-PIGD), 30 PD patients without PIGD (PD-non-PIGD) and 35 Healthy Controls (HCs). Structural networks were constructed using DTI brain white matter fiber tractography. A graph theory approach was applied to characterize the topological properties of complex structural networks, and the relationships between significantly different network metrics and motor deficits were analyzed within the PD-PIGD group. PD-PIGD patients exhibited increased shortest path length compared with PD-non-PIGD and HCs (P < 0.05, respectively). Additionally, PD-PIGD patients exhibited decreased nodal properties, mainly in the cerebellar vermis, prefrontal cortex, paracentral lobule, and visual regions. Notably, the degree centrality of the cerebellar vermis was negatively correlated with the PIGD score (r = -0.390; P = 0.030) and Unified Parkinson\'s Disease Rating Scale Part III score (r = -0.436; P = 0.014) in PD-PIGD patients. Furthermore, network-based statistical analysis revealed decreased structural connectivity between the prefrontal lobe, putamen, supplementary motor area, insula, and cingulate gyrus in PD-PIGD patients. Our findings demonstrated that PD-PIGD patients existed abnormal structural connectomes in the cerebellar vermis, frontal-parietal cortex and visual regions. These topological differences can provide a topological perspective for understanding the potential pathophysiological mechanisms of PIGD in PD.

Individualized treatment guided by biomarkers certainly will play a crucial role in the more effective treatment of various neurological diseases in the near future. Identifying the electroencephalographic biomarkers in the brain of patients with Parkinson\'s disease (PD) may help in the decision-making process of health professionals regarding the non-invasive brain stimulation (NIBS) protocols.
To summarize quantitative electroencephalographic (qEEG) characteristics of patients with PD with motor symptoms at rest or during movement to identify potential biomarker associated with motor impairment in PD.
A systematic search was conducted in the databases MEDLINE/PubMed, LILACS/BIREME, CINAHL/EBSCO, Web of Science, and CENTRAL, performed according to PRISMA-statement guidelines. Two independent authors searched for studies that reported qEEG data related to motor outcomes at rest or during movements in patients with PD and compared the data with control healthy group. The studies\' methodological quality was examined using the Cochrane Handbook. Studies/sample characteristics, qEEG parameters/analyses, and the studies\' results were summarized. Prospero-register: CRD42018085660.
Nineteen studies (18 cross-sectional/one cross-over) with 312 PD patients and 277 controls, published between 1994-2018, were included for the qualitative analysis. In comparison to healthy controls, our findings suggest a slowing down of the cortical activity in patients with PD due to an increase of slower band waves activity and a decrease of fast band waves at resting and during complex movement execution mainly in the central and frontal cortex.
Slowing down of cortical waves suggest excitatory NIBS for motor impairment in PD. However, qEEG biomarker for motor symptoms of PD cannot be established yet because the studies that related qEEG with motor outcomes presented methodological poor quality.

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The aim of this study was to examine non-motor symptoms in different Parkinson\'s disease (PD) motor subtypes and their associations with quality of life (QoL).
A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins\' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson\'s Disease Questionnaire-8.
We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD.
Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients\' QoL.

Parkinson\'s disease (PD) is a circuit-level disorder with clinically-determined motor subtypes. Despite evidence suggesting each subtype may have different pathophysiology, few neuroimaging studies have examined levodopa-induced differences in neural activation between tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtype patients during a motor task. The goal of this functional MRI (fMRI) study was to examine task-induced activation and connectivity in the cortico-striatal-thalamo-cortical motor circuit in healthy controls, TD patients, and PIGD patients before and after levodopa administration. Fourteen TD and 12 PIGD cognitively-intact patients and 21 age- and sex-matched healthy controls completed a right-hand, paced tapping fMRI paradigm. Collectively, PD patients off medication (OFF) showed hypoactivation of the motor cortex relative to healthy controls, even when controlling for performance. After levodopa intake, the PIGD patients had significantly increased activation in the left putamen compared with TD patients and healthy controls. Psychophysiological interaction analysis revealed that levodopa increased effective connectivity between the posterior putamen and other areas of the motor circuit during tapping in TD patients, but not in PIGD patients. This novel, levodopa-induced difference in the neural responses between PD motor subtypes may have significant implications for elucidating the mechanisms underlying the distinct phenotypic manifestations and enabling the classification of motor subtypes objectively using fMRI.

BACKGROUND: Postural instability/gait difficulty (PIGD) and fear of falling (FoF) frequently co-exist, but their individual predictive values for falls have not been compared in aging. This study aims to determine both independent and combined effect of PIGD and FoF to falls in older adults without dementia.
METHODS: PIGD and other extrapyramidal signs were systematically assessed in 449 community-dwelling participants without Parkinson\'s disease (76.48±6.61 ys; 56.8% female) enrolled in this longitudinal cohort study. Presence of FoF was measured by a single-item question (Do you have a FoF?) and self-confidence by the Activities-specific Balance Confidence scale (ABC scale).
RESULTS: One hundred sixty-nine participants (38%) had an incident fall over a mean follow-up of 20.1±12.2months. PIGD was present in 32% and FoF in 23% of the participants. Both PIGD (adjusted hazard ratio (aHR): 2.28; p=0.016) and self-confidence (aHR: 0.99; p=0.040) predicted falls when entered simultaneously in the Cox model. However, presence of FoF (aHR: 1.99; p=0.021) and self-confidence (aHR: 0.98; p=0.006) predicted falls only in individuals with PIGD.
CONCLUSIONS: PIGD and FoF were associated with future falls in older adults without dementia but FoF was a fall\'s predictor only in individuals with PIGD.