The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson’s disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed.

ObjectivesHigher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential ...

Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. Thereby, molecular imaging enables to investigate functional changes and pathological hallmarks in neurodegenerative disorders, thus allowing to better differentiate between different forms of degenerative parkinsonism, improve the accuracy of the clinical diagnosis and disentangle the pathophysiology of disease-related symptoms. The past decade led to significant progress in the field of molecular imaging, including the development of multiple new and promising radioactive tracers for single photon emission computed tomography (SPECT) and positron emission tomography (PET) as well as novel analytical methods. Here, we review the most recent advances in molecular imaging for the diagnosis, prognosis, and mechanistic understanding of parkinsonian disorders. First, advances in imaging of neurotransmission abnormalities, metabolism, synaptic density, inflammation, and pathological protein aggregation are reviewed, highlighting our renewed understanding regarding the multiplicity of neurodegenerative processes involved in parkinsonian disorders. Consequently, we review the role of molecular imaging in the context of disease-modifying interventions to follow neurodegeneration, ensure stratification, and target engagement in clinical trials.

Objectives Anti-IgLON5 disease is a recently discovered neurologic disorder combining autoimmunity and neurodegeneration. Core manifestations include sleep disorders, bulbar symptoms, gait abnormalities, and cognitive dysfunction, but other presentations have been reported. Hallmarks are autoantibodies targeting the neuronal surface protein IgLON5, a strong human leukocyte antigen system Class II association, and brainstem and hypothalamus-dominant tau deposits. The purpose of this cohort study was to visualize tau deposition in vivo with the second-generation tau-PET tracer. Methods A cohort of 4 patients with anti-IgLON5 disease underwent a dynamic PET scan with [18F]PI-2620. One patient received a follow-up scan. Z-deviation maps and a 2-sample t test in comparison with healthy controls (n = 10) were performed. Antibody titers, neurofilament light chain, and disease duration were correlated with brainstem binding potentials. Results Patients demonstrated increased [18F]PI2620 tau binding potentials in the pons, dorsal medulla, and cerebellum. The longitudinal scan after 28 months showed an increase of tracer uptake in the medulla despite immunotherapy. Higher antibody titers and neurofilament light chain correlated with higher tracer retention. Discussion The results indicate that tau depositions in anti-IgLON5 disease can be visualized with [18F]PI-2620 and might correlate with the extent of disease. For validation, a larger longitudinal study is necessary.

The spatial extent of amyloid, tau, and neurodegeneration, derived from PET imaging, has higher diagnostic performance for cognitive impairment severity compared with standardized uptake value ratios.

Disorders characterized by changes in dopamine (DA) neurotransmission are often linked to changes in the temporal discounting of future rewards. Likewise, pharmacological manipulations of DA neurotransmission in healthy individuals modulate temporal discounting, but there is considerable variability in the directionality of reported pharmacological effects, as enhancements and reductions of DA signaling have been linked to both increases and reductions of temporal discounting. This may be due to meaningful individual differences in drug effects and/or false-positive findings in small samples. To resolve these inconsistencies, we (1) revisited pharmacological effects of the DA precursor l -DOPA on temporal discounting in a large sample of N = 76 healthy participants ( n = 44 male) and (2) examined several putative proxy measures for DA to revisit the role of individual differences in a randomized, double-blind placebo–controlled preregistered study ( https://osf.io/a4k9j/ ). Replicating previous findings, higher rewards were discounted less (magnitude effect). Computational modeling using hierarchical Bayesian parameter estimation confirmed that the data in both drug conditions were best accounted for by a nonlinear temporal discounting drift diffusion model. In line with recent animal and human work, l -DOPA reliably reduced the discount rate with a small effect size, challenging earlier findings in substantially smaller samples. We found no credible evidence for effects of putative DA proxy measures on model parameters, calling into question the role of these measures in accounting for individual differences in DA drug effects.