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.

Background: α‐Synuclein pathology is associated with neuronal degeneration in Parkinson's disease (PD) and considered to sequentially spread across the brain (Braak stages). According to a new hypothesis of distinct α‐synuclein spreading directions based on the initial site of pathology, the “brain‐first” spreading subtype would be associated with a more asymmetric cerebral and nigrostriatal pathology than the “body‐first” subtype.Objective: Here, we tested if proposed markers of brain‐first PD (ie, higher dopamine transporter [DaT] asymmetry; absence of rapid eye movement sleep behavior disorder [RBD]) are associated with a greater or more asymmetric reduction in gray matter volume (GMV) in comparison to body‐first PD.Methods: Data of 255 de novo PD patients and 110 healthy controls (HCs) were retrieved from the Parkinson's Progression Markers Initiative. Structural magnetic resonance images were preprocessed, and GMVs and their hemispherical asymmetry were obtained for each of the neuropathologically defined Braak stages. Group and correlation comparisons were performed to assess differences in GMV and GMV asymmetry between PD subtypes.Results: PD patients demonstrated significantly smaller bilateral GMVs compared to HCs, in a pattern denoting stage‐dependent disease‐related brain atrophy. However, the degree of putaminal DaT asymmetry was not associated with reduced GMV or higher GMV asymmetry. Furthermore, RBD‐negative and RBD‐positive patients did not demonstrate a significant difference in GMV or GMV asymmetry.Conclusions: Our findings suggest that putative brain‐first and body‐first patients do not present diverging brain atrophy patterns. Although certainly not disproving the brain‐first/body‐first spreading hypothesis, this study fails to provide evidence in support of it. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Tauopathies are a heterogeneous group of neurologic diseases characterized by pathological axodendritic distribution, ectopic expression, and/or phosphorylation and aggregation of the microtubule-associated protein TAU, encoded by the gene MAPT. Neuronal dysfunction, dementia, and neurodegeneration are common features of these often detrimental diseases. A neurodegenerative disease is considered a primary tauopathy when MAPT mutations/haplotypes are its primary cause and/or TAU is the main pathological feature. In case TAU pathology is observed but superimposed by another pathological hallmark, the condition is classified as a secondary tauopathy. In some tauopathies (e.g. MAPT-associated frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Alzheimer's disease (AD)) TAU is recognized as a significant pathogenic driver of the disease. In many secondary tauopathies, including Parkinson's disease (PD) and Huntington's disease (HD), TAU is suggested to contribute to the development of dementia, but in others (e.g. Niemann-Pick disease (NPC)) TAU may only be a bystander. The genetic and pathological mechanisms underlying TAU pathology are often not fully understood. In this review, the genetic predispositions and variants associated with both primary and secondary tauopathies are examined in detail, assessing evidence for the role of TAU in these conditions. We highlight less common genetic forms of tauopathies to increase awareness for these disorders and the involvement of TAU in their pathology. This approach not only contributes to a deeper understanding of these conditions but may also lay the groundwork for potential TAU-based therapeutic interventions for various tauopathies.

Compensatory mechanisms in Parkinson’s disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson’s disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson’s disease, the underlying pathophysiology is unclear. Here, we investigate motor compensation in Parkinson’s disease by investigating the relationship between clinical signs, dopamine transporter imaging data and neurophysiological measures of the primary motor cortex (M1), using transcranial magnetic stimulation in presymptomatic and symptomatic hemispheres of patients. In this cross-sectional, multicentre study, we screened 82 individuals with Parkinson’s disease. Patients were evaluated clinically in their medication OFF state using standardized scales. Sixteen Parkinson’s disease patients with bilateral dopamine transporter deficit in the putamina but unilateral symptoms were included. Twenty-eight sex- and age-matched healthy controls were also investigated. In all participants, we tested cortical excitability using single- and paired-pulse techniques, interhemispheric inhibition and cortical plasticity with paired associative stimulation. Data were analysed with ANOVAs, multiple linear regression and logistic regression models. Individual coefficients of motor compensation were defined in patients based on clinical and imaging data, i.e. the motor compensation coefficient. The motor compensation coefficient includes an asymmetry score to balance motor and dopamine transporter data between the two hemispheres, in addition to a hemispheric ratio accounting for the relative mismatch between the magnitude of motor signs and dopaminergic deficit. In patients, corticospinal excitability and plasticity were higher in the presymptomatic compared with the symptomatic M1. Also, interhemispheric inhibition from the presymptomatic to the symptomatic M1 was reduced. Lower putamen binding was associated with higher plasticity and reduced interhemispheric inhibition in the presymptomatic hemisphere. The motor compensation coefficient distinguished the presymptomatic from the symptomatic hemisphere. Finally, in the presymptomatic hemisphere, a higher motor compensation coefficient was associated with lower corticospinal excitability and interhemispheric inhibition and with higher plasticity. In conclusion, the present study suggests that motor compensation involves M1–striatal networks and intercortical connections becoming more effective with progressive loss of dopaminergic terminals in the putamen. The balance between these motor networks seems to be driven by cortical plasticity.