Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology.

INTRODUCTION: The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes. METHODS: Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity. RESULTS: Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance. CONCLUSIONS: The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.

Electrical stimulation of the nucleus basalis of meynert: a systematic review of preclinical and clinical data.

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been clinically investigated in Alzheimer's disease (AD) and Lewy body dementia (LBD). However, the clinical effects are highly variable, which questions the suggested basic principles underlying these clinical trials. Therefore, preclinical and clinical data on the design of NBM stimulation experiments and its effects on behavioral and neurophysiological aspects are systematically reviewed here. Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow, released several neuroprotective factors, and facilitates plasticity of cortical and subcortical receptive fields. However, the translation of these outcomes to current clinical practice is hampered by the fact that mainly animals with an intact NBM were used, whereas most animals were stimulated unilaterally, with different stimulation paradigms for only restricted timeframes. Future animal research has to refine the NBM stimulation methods, using partially lesioned NBM nuclei, to better resemble the clinical situation in AD, and LBD. More preclinical data on the effect of stimulation of lesioned NBM should be present, before DBS of the NBM in human is explored further.

Relationship between Paternal and Maternal Parenting Style with Internet Addiction Level of Adolescents.

Objective: Internet addiction has become a major problem worldwide, especially for adolescents. Adolescents are considered vulnerable and at risk of internet addiction due to the immature self-control, easy access, and flexible schedule. Parenting style has a significant influence on the incidence of internet addiction in adolescents. This study aimed to analyze the relationship between paternal and maternal parenting style toward internet addiction level of adolescents at one of junior high Schools in Surabaya, Indonesia. Method : In this cross-sectional study, a total of 114 adolescents (44 boys and 70 girls) aged ranging from 12 to 15 in a junior high school in Surabaya, Indonesia, were recruited by stratified random sampling method in November 2019. The Internet Addiction Test (IAT) and Parental Authority Questionnaire (PAQ) were used to measure internet addiction level, and maternal and paternal parenting style of adolescents. The data were analyzed using Pearson correlation and multiple regression tests with IBM SPSS Statistics 25 to adjust the relationship between paternal and maternal parenting style toward internet addiction level of adolescents. Results: a total of 77.2% of adolescents were internet addicts and the majority experienced 'mild' internet addiction level (52.60%). Furthermore, the Pearson correlation results indicated that paternal permissive and authoritarian parenting styles were positively correlated with internet addiction level of adolescents. The multiple regression analysis results indicated that paternal permissive parenting style significantly predicted adolescents' internet addiction level. Conclusion: This study highlighted the significant role of paternal permissive and authoritarian parenting styles among adolescents' internet addiction.

Oscillatory activity and cortical coherence of the nucleus basalis of Meynert in Parkinson's disease dementia.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is a new potential treatment for Parkinson's Disease dementia (PDD) and other types of dementia. To get a better understanding of this structure, its local neurophysiological properties and cortical connectivity patterns were studied. METHODS: We simultaneously recorded DBS local field potentials (LFPs) and electroencephalography (EEG) in two patients with PDD. Both patients had DBS electrodes in the internal globus pallidus (GPi) with one or more distal contacts close to or inside the NBM. Measurements were obtained during routine battery replacement. The distance of DBS contacts to the NBM were calculated using CT-MRI fusion. RESULTS: Delta (1-4 Hz) oscillations were more prominently present in the NBM region than in its vicinity, whereas temporal coherence in the theta (4-8 Hz) range was less outspoken. CONCLUSION: These neurophysiological characteristics, if also proven in larger cohorts, might help to map the NBM more precisely during electrode implantation.

MMP7 cleaves remyelination-impairing fibronectin aggregates and its expression is reduced in chronic multiple sclerosis lesions.

Upon demyelination, transient expression of fibronectin precedes successful remyelination. However, in chronic demyelination observed in multiple sclerosis (MS), aggregates of fibronectin persist and contribute to remyelination failure. Accordingly, removing fibronectin (aggregates) would constitute an effective strategy for promoting remyelination. Matrix metalloproteinases (MMPs) are enzymes known to remodel extracellular matrix components, including fibronectin. Here, we examined the ability of MMPs to degrade fibronectin aggregates. Our findings reveal that MMP7 cleaved fibronectin aggregates resulting into a prominent 13 kDa EIIIA (16 kDa EDA)-containing fragment. MMP7 was upregulated during lysolecithin-induced demyelination, indicating its potential for endogenous fibronectin clearance. In contrast, the expression of proMMP7 was substantially decreased in chronic active and inactive MS lesions compared with control white matter and remyelinated MS lesions. Microglia and macrophages were major cellular sources of proMMP7 and IL-4-activated, but not IFNγ+LPS-activated, microglia and macrophages secreted significant levels of proMMP7. Also, conditioned medium of IL-4-activated macrophages most efficiently cleaved fibronectin aggregates upon MMP-activating conditions. Yet, coatings of MMP7-cleaved fibronectin aggregate fragments inhibited oligodendrocyte maturation, indicating that further degradation and/or clearance by phagocytosis is essential. These findings suggest that MMP7 cleaves fibronectin aggregates, while reduced (pro)MMP7 levels in MS lesions contribute to their persistent presence. Therefore, upregulating MMP7 levels may be key to remove remyelination-impairing fibronectin aggregates in MS lesions.