Here we test the hypothesis that the neurodegenerative process in Parkinson’s disease (PD) moves stereotypically along neural networks, possibly reflecting the spread of toxic alpha-synuclein molecules. PD patients (n = 105) and matched controls (n = 57) underwent T1-MRI at entry and 1 year later as part of the Parkinson’s Progression Markers Initiative. Over this period, PD patients demonstrate significantly greater cortical thinning than controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical thinning is correlated to connectivity (measured functionally or structurally) to a “disease reservoir” evaluated by MRI at baseline. The atrophy pattern in the ventral frontal lobes resembles one described in certain cases of Alzheimer’s disease. Our findings suggest that disease propagation to the cortex in PD follows neuronal connectivity and that disease spread to the cortex may herald the onset of cognitive impairment.

Addiction professionals and the public are recognizing that certain nonsubstance behaviors—such as gambling, Internet use, video-game playing, sex, eating, and shopping—bear resemblance to alcohol and drug dependence. Growing evidence suggests that these behaviors warrant consideration as nonsubstance or “behavioral” addictions and has led to the newly introduced diagnostic category “Substance-Related and Addictive Disorders” in DSM-5. At present, only gambling disorder has been placed in this category, with insufficient data for other proposed behavioral addictions to justify their inclusion. This review summarizes recent advances in our understanding of behavioral addictions, describes treatment considerations, and addresses future directions. Current evidence points to overlaps between behavioral and substance-related addictions in phenomenology, epidemiology, comorbidity, neurobiological mechanisms, genetic contributions, responses to treatments, and prevention efforts. Differences also exist. Recognizing behavioral addictions and developing appropriate diagnostic criteria are important in order to increase awareness of these disorders and to further prevention and treatment strategies.

It is becoming increasingly clear that brain network organization shapes the course and expression of neurodegenerative diseases. Parkinson disease (PD) is marked by progressive spread of atrophy from the midbrain to subcortical structures and, eventually, to the cerebral cortex. Recent discoveries suggest that the neurodegenerative process involves the misfolding and prion-like propagation of endogenous α-synuclein via axonal projections. However, the mechanisms that translate local "synucleinopathy" to large-scale network dysfunction and atrophy remain unknown. Here, we use an agent-based epidemic spreading model to integrate structural connectivity, functional connectivity, and gene expression and to predict sequential volume loss due to neurodegeneration. The dynamic model replicates the spatial and temporal patterning of empirical atrophy in PD and implicates the substantia nigra as the disease epicenter. We reveal a significant role for both connectome topology and geometry in shaping the distribution of atrophy. The model also demonstrates that SNCA and GBA transcription influence α-synuclein concentration and local regional vulnerability. Functional coactivation further amplifies the course set by connectome architecture and gene expression. Altogether, these results support the theory that the progression of PD is a multifactorial process that depends on both cell-to-cell spreading of misfolded proteins and regional vulnerability.

Given the prevalence of Internet use among youth, there is concern that a subset of Internet-using youth may exhibit problematic or addictive patterns of Internet use. The present study examines the association between problematic Internet use (PIU), demographic variables, and health-related measures among Chinese adolescents. Survey data from 1552 adolescents (male = 653, mean age = 15.43 years) from Jilin Province, China, were collected. According to the Young Diagnostic Questionnaire for Internet Addiction (YDQ), 77.8% (n=1,207), 16.8% (n=260), and 5.5% (n=85) showed adaptive, maladaptive, and problematic Internet use, respectively. Multinomial logistic regression analysis revealed that gender and family income per month differed between youth showing problematic and adaptive patterns of Internet use. Well-being, self-esteem, and self-control were related to severity of problematic Internet use, with greater severity typically associated with poorer measures in each domain. The findings that severity of problematic Internet use is associated with specific socio-demographic features and temperamental and well-being measures suggest that specific groups of youth may be particularly vulnerable to developing problematic Internet use. Early prevention/intervention programs targeting at-risk groups may help improve public health.

Parkinson’s disease varies in severity and age of onset. One source of this variability is sex. Males are twice as likely as females to develop Parkinson’s disease, and tend to have more severe symptoms and greater speed of progression. However, to date, there is little information in large cohorts on sex differences in the patterns of neurodegeneration. Here we used MRI and clinical information from the Parkinson Progression Markers Initiative to measure structural brain differences between sexes in Parkinson’s disease after regressing out the expected effect of age and sex. We derived atrophy maps from deformation-based morphometry of T1-weighted MRI and connectivity from diffusion-weighted MRI in de novo Parkinson’s disease patients (149 males: 83 females) with comparable clinical severity, and healthy control participants (78 males: 39 females). Overall, even though the two patient groups were matched for disease duration and severity, males demonstrated generally greater brain atrophy and disrupted connectivity. Males with Parkinson’s disease had significantly greater tissue loss than females in 11 cortical regions including bilateral frontal and left insular lobe, right postcentral gyrus, left inferior temporal and cingulate gyrus and left thalamus, while females had greater atrophy in six cortical regions, including regions in the left frontal lobe, right parietal lobe, left insular gyrus and right occipital cortex. Local efficiency of white matter connectivity showed greater disruption in males in multiple regions such as basal ganglia, hippocampus, amygdala and thalamus. These findings support the idea that development of Parkinson’s disease may involve different pathological mechanisms and yield distinct prognosis in males and females, which may have implications for research into neuroprotection, and stratification for clinical trials.

White Matter Hyperintensities (WMHs) are associated with cognitive decline in aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in Parkinson's disease (PD) is not as clearly related to vascular causes, and therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is less clear. Currently, SVD in PD is assessed and treated independently of the disease. However, if WMH as the major MRI sign of SVD has a higher impact on cognitive decline in PD patients than in healthy controls, vascular pathology needs to be assessed and treated with a higher priority in this population. Here we investigate whether the presence of WMHs leads to increased cognitive decline in de novo PD, and if these effects relate to cortical atrophy. WMHs and cortical thickness were measured in de novo PD patients and age-matched controls (NPD = 365, NControl = 174) from Parkinson's Progression Markers Initiative (PPMI) to study the relationship between baseline WMHs, future cognitive decline (follow-up: 4.09 ± 1.14 years) and cortical atrophy (follow-up: 1.05 ± 0.10 years). PD subjects with high baseline WMH loads had significantly greater cognitive decline than i) PD subjects with low WMH load, and ii) control subjects with high WMH load. Furthermore, in PD subjects, high WMH load resulted in more cortical thinning in the right frontal lobe. Theses results show that the presence of WMHs in de novo PD patients predicts greater future cognitive decline and cortical atrophy than in normal aging.

While the conceptualization of problematic Internet use (PIU) as a ‘behavioral addiction’ resembling substance-use disorders is debated, the neurobiological underpinnings of PIU remain understudied. This study examined whether adolescents displaying features of PIU (at-risk PIU; ARPIU) are more impulsive and exhibit blunted responding in the neural mechanisms underlying feedback processing and outcome evaluation during risk-taking. Event-related potentials (ERPs) elicited by positive (i.e. reward) and negative (i.e. loss) feedback were recording during performance on a modified version of the Balloon Analogue Risk Task (BART) among ARPIU (n=39) and non-ARPIU subjects (n=27). Compared to non-ARPIU, ARPIU adolescents displayed higher levels of urgency and lack of perseverance on the UPPS Impulsive Behavior Scale. Although no between-group difference in BART performance was observed, ERPs demonstrated overall decreased sensitivity to feedback in ARPIU compared to non-ARPIU adolescents, as indexed by blunted feedback-related negativity (FRN) and P300 amplitudes to both negative and positive feedback. The present study provides evidence for feedback processing during risk-taking as a neural correlate of ARPIU. Given recent concerns regarding the growing prevalence of PIU as a health concern, future work should examine the extent to which feedback processing may represent a risk factor for PIU, a consequence of PIU, or possibly both.

It is becoming increasingly clear that brain network organization shapes the course and expression of neurodegenerative diseases. Parkinson's disease (PD) is marked by progressive spread of atrophy from the midbrain to subcortical structures and eventually, to the cerebral cortex. Recent discoveries suggest that the neurodegenerative process involves the misfolding and prion-like propagation of endogenous α-synuclein via axonal projections. However, the mechanisms that translate local "synucleinopathy" to large-scale network dysfunction and atrophy remain unknown. Here we use an agent-based epidemic spreading model to integrate structural connectivity, functional connectivity and gene expression, and to predict sequential volume loss due to neurodegeneration. The dynamic model replicates the spatial and temporal patterning of empirical atrophy in PD and implicates the substantia nigra as the disease epicenter. We reveal a significant role for both connectome topology and geometry in shaping the distribution of atrophy. The model also demonstrates that SNCA and GBA transcription influence α-synuclein concentration and local regional vulnerability. Functional co-activation further amplifies the course set by connectome architecture and gene expression. Altogether, these results support the theory that the progression of PD is a multifactorial process that depends on both cell-to-cell spreading of misfolded proteins and regional vulnerability.Neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), 2 and Amyotrophic Lateral Sclerosis, are a major cause of psychosocial burden and 3 mortality, but lack specific therapy. Until recently, the mechanism of progressive 4 neuronal death in these conditions was unknown. However, converging lines of evidence 5 from molecular, animal and human postmortem studies point to misfolded neurotoxic 6 proteins that propagate through the central nervous system via neuronal 7 connections [1-6]. These pathogenic misfolded disease-specific proteins function as 8 corruptive templates that induce their normal protein counterparts to adopt a similar 9 conformational alteration, analogous to the self-replication process in prion diseases. 10Examples include amyloid β-protein (Aβ) and tau in AD and α-synuclein in PD. The 11 November 1, 2019 1/26 misfolded proteins can deposit into insoluble aggregates and progressively spread to 12 interconnected neuronal populations through synaptic connections. The model of a 13propagating proteinopathy remains controversial however [7], and direct evidence in 14 humans remains mostly circumstantial [8]. 15The prion hypothesis suggests that propagation dynamics in neurodegenerative 16 diseases may be modeled using methods derived from infectious disease epidemiology. 17Just as infectious diseases spread via social contact networks, misfolded proteins 18 propagate via the brain's connectome. There are different approaches for modeling 19 epidemic spread over a network. In simple diffusion models, disease in any region is 20 model...