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Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O 2 and CO 2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O 2 and CO 2 tables., Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O 2 table and CO 2 table. During apnea, peripheral oxygen saturation (SpO 2 ), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO 2 ) was measured before and after apneas., Results: Larger lung volumes, higher resting cTOI and lower resting EtCO 2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO 2 (- 16%) and cTOI (- 13%) than O 2 (- 8%; - 8%) and CO 2 tables (- 6%; - 6%), whereas changes in EtCO 2 , HR and mTOI did not differ between protocols., Conclusion: These results suggest that, in apnea novices, O 2 and CO 2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity., Competing Interests: Declarations Competing interests The authors declare that they have no competing interest. Consent to participate A written informed consent was obtained from all individual participants included in the study. Consent to publish Not applicable. Ethics approval “All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethical committee of the Ghent University Hospital (EC UZG 2018/0221) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acute breath-holding (apnoea) induces a spleen contraction leading to a transient increase in haemoglobin concentration. Additionally, the apnoea-induced hypoxia has been shown to lead to an increase in erythropoietin concentration up to 5 h after acute breath-holding, suggesting long-term haemoglobin enhancement. Given its potential to improve haemoglobin content, an important determinant for oxygen transport, apnoea has been suggested as a novel training method to improve aerobic performance. This review aims to provide an update on the current state of the literature on this topic. Although the apnoea-induced spleen contraction appears to be effective in improving oxygen uptake kinetics, this does not seem to transfer into immediately improved aerobic performance when apnoea is integrated into a warm-up. Furthermore, only long and intense apnoea protocols in individuals who are experienced in breath-holding show increased erythropoietin and reticulocytes. So far, studies on inexperienced individuals have failed to induce acute changes in erythropoietin concentration following apnoea. As such, apnoea training protocols fail to demonstrate longitudinal changes in haemoglobin mass and aerobic performance. The low hypoxic dose, as evidenced by minor oxygen desaturation, is likely insufficient to elicit a strong erythropoietic response. Apnoea therefore does not seem to be useful for improving aerobic performance. However, variations in apnoea, such as hypoventilation training at low lung volume and repeated-sprint training in hypoxia through short end-expiratory breath-holds, have been shown to induce metabolic adaptations and improve several physical qualities. This shows promise for application of dynamic apnoea in order to improve exercise performance. HIGHLIGHTS: What is the topic of this review? Apnoea is considered as an innovative method to improve performance. This review discusses the effectiveness of apnoea (training) on performance. What advances does it highlight? Although the apnoea-induced spleen contraction and the increase in EPO observed in freedivers seem promising to improve haematological variables both acutely and on the long term, they do not improve exercise performance in an athletic population. However, performing repeated sprints on end-expiratory breath-holds seems promising to improve repeated-sprint capacity., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: To investigate the relationship between oral muscle pressure and malocclusion in the mixed dentition., Materials and Methods: Maximum tongue, lip and cheek pressure was measured using the Iowa Oral Performance Instrument (IOPI) in 3 patient cohorts: patients with (1) posterior crossbite, (2) class II relationship and (3) a control group of patients without malocclusion. Linear models were used to compare the mean differences in muscle pressure between groups, with correction for age and gender. The imbalance between lips and tongue and between lips and cheeks was calculated by the Delta z-scores of each group., Results: A total of 146 participants were included, 46 (mean age 8.71±0.85), 41 (mean age 11.74±1.17) and 35 (mean age 10.71±1.92) in groups 1, 2 and 3 respectively. Patients with malocclusion showed significantly higher lip and lower cheek pressure and imbalance favouring the lips over the tongue compared to controls. Class II,1 patients showed significantly higher tongue pressure than Class II,2. No differences were found in muscle pressure or imbalance between crossbite and Class II nor between crossbite types., Conclusion and Clinical Relevance: These findings suggest that oral muscle pressure may be associated with malocclusion. This highlights the importance of functional diagnosis and its implications on the prevention and treatment of malocclusion, as well as on orthodontic stability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings., Competing Interests: Competing interests: EV is Editor in Chief of BMJ Open Sports & Exercise Medicine., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Photobiomodulation (PBM) is rapidly gaining traction as a valuable tool in dermatology for treating many inflammatory skin conditions using low levels of visible light or near-infrared radiation. However, the physiological regulatory pathways responsible for the anti-inflammatory effect of PBM have not been well defined. Since previous studies showed that nuclear factor-erythroid 2 like 2 (Nrf2) is a master regulator of the skin inflammatory response, we have addressed its role in controlling inflammation by PBM. Primary human keratinocytes (KCs) stimulated with 2,4-dinitrochlorobenzene (DNCB) to mimic pro-inflammatory stress were illuminated with two wavelengths: 660 nm or 520 nm. Both lights significantly reduced the mRNA expression of the DNCB-triggered TNF-α , IL-6 , and IL-8 cytokines in KCs, while they enhanced Nrf2 pathway activation. PBM-induced Nrf2 is a key regulator of the inflammatory response in KCs since its absence abolished the regulatory effect of light on cytokines production. Further investigations of the mechanisms contributing to the immunoregulatory effect of PBM in inflamed human skin explants showed that 660 nm light prevented Langerhans cells migration into the dermis, preserving their dendricity, and decreased pro-inflammatory cytokine production compared to the DNCB-treated group. This study is the first to report that the PBM-mediated anti-inflammatory response in KCs is Nrf2-dependent and further support the role of PBM in skin immunomodulation. Therefore, PBM should be considered a promising alternative or complementary therapeutic approach for treating skin-related inflammatory diseases.

Palmitoylation is a lipid modification involving the attachment of palmitic acid to a cysteine residue, thereby affecting protein function. We investigated the effect of palmitoylation of tyrosinase, the rate-limiting enzyme in melanin synthesis, using a human three-dimensional skin model system and melanocyte culture. The palmitoylation inhibitor, 2-bromopalmitate, increased melanin content and tyrosinase protein levels in melanogenic cells by suppressing tyrosinase degradation. The palmitoylation site was Cysteine 500 in the C-terminal cytoplasmic tail of tyrosinase. The nonpalmitoylatable mutant, tyrosinase (C500A), was slowly degraded and less ubiquitinated than wild-type tyrosinase. Screening for the Asp-His-His-Cys (DHHC) family of proteins for tyrosinase palmitoylation suggested that DHHC2, 3, 7, and 15 are involved in tyrosinase palmitoylation. Knockdown of DHHC2, 3, or 15 increased tyrosinase protein levels and melanin content. Determination of their subcellular localization in primary melanocytes revealed that DHHC2, 3, and 15 were localized in the endoplasmic reticulum, Golgi apparatus, and/or melanosomes, whereas only DHHC2 was localized in the melanosomes. Immunoprecipitation showed that DHHC2 and DHHC3 predominantly bind to mature and immature tyrosinase, respectively. Taken together, tyrosinase palmitoylation at Cysteine 500 by DHHC2, 3, and/or 15, especially DHHC2 in trans-Golgi apparatus and melanosomes and DHHC3 in the endoplasmic reticulum and cis-Golgi apparatus, regulate melanogenesis by modulating tyrosinase protein levels., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute apnea is known to induce decreases in oxyhemoglobin desaturation (SpO 2 ) and increases in erythropoietin concentration ([EPO]). This study examined the potential of an apnea training program to induce erythropoiesis and increase hematological parameters and exercise performance. Twenty-two male subjects were randomly divided into an apnea and control group. The apnea group performed a 6-wk apnea training program consisting of a daily series of five maximal static apneas. Before and after training, subjects visited the lab on 3 test days to perform 1 ) a ramp incremental test measuring V̇o 2peak , 2 ) CO-rebreathing for Hbmass determination and a 3-km time trial, and 3 ) an apnea test protocol with continuous finger SpO 2 registration. Venous blood samples were drawn before and 180 min after the apnea test for analysis of [EPO]. Minimal SpO 2 reached during the apnea test protocol was 91 ± 7% pre and 82 ± 7% post apnea training. The apnea test protocol did not elicit an acute increase in [EPO] ( P = 0.685) before nor after the training program. Consequently, resting [EPO] ( P = 0.170), Hbmass ( P = 0.134), V̇o 2peak ( P = 0.796), and 3-km cycling time trial performance ( P = 0.509) were not affected either. The apnea test and training protocol, consisting of five maximal static apneas, did not induce a sufficiently strong hypoxic stimulus to cause erythropoiesis and therefore did not result in an increase in resting [EPO], Hbmass, V̇o 2peak , or time trial performance. Longer and/or more intense training sessions inducing a stronger hypoxic stimulus are probably needed to obtain changes in hematological and exercise parameters. NEW & NOTEWORTHY Apnea training has been suggested as a promising method to improve exercise performance for over a decade. However, to our knowledge, this study is the first to evaluate its value on both hematological parameters and exercise performance, including Hbmass and a control group. No changes in Hbmass nor exercise performance were observed. Contradicting previous research, no acute increase in [EPO] following apnea was observed either, indicating that more intense protocols are needed, at least in nonapnea-trained individuals.

To conduct a multilevel meta-analysis of multiple single-case experimental design (SCED) studies, the individual participant data (IPD) can be analyzed in one or two stages. In the one-stage approach, a multilevel model is estimated based on the raw data. In the two-stage approach, an effect size is calculated for each participant and these effect sizes and their sampling variances are subsequently combined to estimate a meta-analytic multilevel model. The multilevel model in the two-stage approach has fewer parameters to estimate, in exchange for the reduction of information of the raw data to effect sizes. In this paper we explore how the one-stage and two-stage IPD approaches can be applied in the context of meta-analysis of single-case designs. Both approaches are compared for several single-case designs of increasing complexity. Through a simulation study we show that the two-stage approach obtains better convergence rates for more complex models, but that model estimation does not necessarily converge at a faster speed. The point estimates of the fixed effects are unbiased for both approaches across all models, as such confirming results from methodological research on IPD meta-analysis of group-comparison designs. In light of these results, we discuss the implementation of both methods in R.

In meta-analysis, primary studies often include multiple, dependent effect sizes. Several methods address this dependency, such as the multivariate approach, three-level models, and the robust variance estimation (RVE) method. As for today, most simulation studies that explore the performance of these methods have focused on the estimation of the overall effect size. However, researchers are sometimes interested in obtaining separate effect size estimates for different types of outcomes. A recent simulation study (Park & Beretvas, 2019) has compared the performance of the three-level approach and the RVE method in estimating outcome-specific effects when several effect sizes are reported for different types of outcomes within studies. The goal of this paper is to extend that study by incorporating additional simulation conditions and by exploring the performance of additional models, such as the multivariate model, a three-level model that specifies different study-effects for each type of outcome, a three-level model that specifies a common study-effect for all outcomes, and separate three-level models for each type of outcome. Additionally, we also tested whether the a posteriori application of the RV correction improves the standard error estimates and the 95% confidence intervals. Results show that the application of separate three-level models for each type of outcome is the only approach that consistently gives adequate standard error estimates. Also, the a posteriori application of the RV correction results in correct 95% confidence intervals in all models, even if they are misspecified, meaning that Type I error rate is adequate when the RV correction is implemented.

Skin structure and function results from a dynamic interplay between dermal and epidermal cell types. Optimizing skin health through an effective and long-lasting skin care regime therefore requires a global approach, encompassing various mechanisms to stimulate this interplay beyond the action scope of a classical topical solution. This study evaluates the impact of a novel home-use device combining a topical serum, light-emitting diodes and massage on the clinical signs of extrinsic skin aging. The innovative principle relies on potentiating the effect of active ingredients contained in the topical serum with visible and near infra-red photons to prevent extracellular matrix degradation and promote its reconstruction. After in vitro and ex vivo investigations, a clinical study assessed the safety and efficacy of a daily treatment with the home-use device for 28 days. A significant increases in skin density and radiance while reducing the wrinkles was obtained with no side effects., (© 2020 LightInDerm. Journal of Biophotonics published by WILEY-VCH GmbH.)

The focus of the current study is on handling the dependence among multiple regression coefficients representing the treatment effects when meta-analyzing data from single-case experimental studies. We compare the results when applying three different multilevel meta-analytic models (i.e., a univariate multilevel model avoiding the dependence, a multivariate multilevel model ignoring covariance at higher levels, and a multivariate multilevel model modeling the existing covariance) to deal with the dependent effect sizes. The results indicate better estimates of the overall treatment effects and variance components when a multivariate multilevel model is applied, independent of modeling or ignoring the existing covariance. These findings confirm the robustness of multilevel modeling to misspecifying the existing covariance at the case and study level in terms of estimating the overall treatment effects and variance components. The results also show that the overall treatment effect estimates are unbiased regardless of the underlying model, but the between-case and between-study variance components are biased in certain conditions. In addition, the between-study variance estimates are particularly biased when the number of studies is smaller than 40 (i.e., 10 or 20) and the true value of the between-case variance is relatively large (i.e., 8). The observed bias is larger for the between-case variance estimates compared to the between-study variance estimates when the true between-case variance is relatively small (i.e., 0.5).

In meta-analysis, study participants are nested within studies, leading to a multilevel data structure. The traditional random effects model can be considered as a model with a random study effect, but additional random effects can be added in order to account for dependent effects sizes within or across studies. The goal of this systematic review is three-fold. First, we will describe how multilevel models with multiple random effects (i.e., hierarchical three-, four-, five-level models and cross-classified random effects models) are applied in meta-analysis. Second, we will illustrate how in some specific three-level meta-analyses, a more sophisticated model could have been used to deal with additional dependencies in the data. Third and last, we will describe the distribution of the characteristics of multilevel meta-analyses (e.g., distribution of the number of outcomes across studies or which dependencies are typically modeled) so that future simulation studies can simulate more realistic conditions. Results showed that four- or five-level or cross-classified random effects models are not often used although they might account better for the meta-analytic data structure of the analyzed datasets. Also, we found that the simulation studies done on multilevel meta-analysis with multiple random factors could have used more realistic simulation factor conditions. The implications of these results are discussed, and further suggestions are given.

Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare 18 F-DPA714, a second-generation translocator protein tracer, with 11 C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with 18 F-DPA714 and 11 C-JNJ717 was performed on human ALS brain sections in comparison to immunofluorescence with Iba1 and GFAP. For the in vivo portion, 3 male patients with early-stage ALS (59.3 ± 7.2 y old) and 6 healthy volunteers (48.2 ± 16.5 y old, 2 men and 4 women) underwent dynamic PET/MR scanning with 18 F-DPA714 and 11 C-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in 11 C-JNJ717 binding but did show increased 18 F-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in 18 F-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, 18 F-DPA714 showed increased signal whereas 11 C-JNJ717 was not elevated., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Pain-related fear is typically associated with avoidance behavior and pain-related disability in youth with chronic pain. Youth with elevated pain-related fear have attenuated treatment responses; thus, targeted treatment is highly warranted. Evidence supporting graded in vivo exposure treatment (GET) for adults with chronic pain is considerable, but just emerging for youth. The current investigation represents the first sequential replicated and randomized single-case experimental phase design with multiple measures evaluating GET for youth with chronic pain, entitled GET Living. A cohort of 27 youth (81% female) with mixed chronic pain completed GET Living. For each participant, a no-treatment randomized baseline period was compared with GET Living and 3- and 6-month follow-ups. Daily changes in primary outcomes fear and avoidance and secondary outcomes pain catastrophizing, pain intensity, and pain acceptance were assessed using electronic diaries and subjected to descriptive and model-based inference analyses. Based on individual effect size calculations, a third of participants significantly improved by the end of treatment on fear, avoidance, and pain acceptance. By follow-up, over 80% of participants had improved across all primary and secondary outcomes. Model-based inference analysis results to examine the series of replicated cases were generally consistent. Improvements during GET Living was superior to the no-treatment randomized baseline period for avoidance, pain acceptance, and pain intensity, whereas fear and pain catastrophizing did not improve. All 5 outcomes emerged as significantly improved at 3- and 6-month follow-ups. The results of this replicated single-case experimental phase design support the effectiveness of graded exposure for youth with chronic pain and elevated pain-related fear avoidance.

The MultiSCED web application has been developed to assist applied researchers in behavioral sciences to apply multilevel modeling to quantitatively summarize single-case experimental design (SCED) studies through a user-friendly point-and-click interface embedded within R. In this paper, we offer a brief introduction to the application, explaining how to define and estimate the relevant multilevel models and how to interpret the results numerically and graphically. The use of the application is illustrated through a re-analysis of an existing meta-analytic dataset. By guiding applied researchers through MultiSCED, we aim to make use of the multilevel modeling technique for combining SCED data across cases and across studies more comprehensible and accessible.

When (meta-)analyzing single-case experimental design (SCED) studies by means of hierarchical or multilevel modeling, applied researchers almost exclusively rely on the linear mixed model (LMM). This type of model assumes that the residuals are normally distributed. However, very often SCED studies consider outcomes of a discrete rather than a continuous nature, like counts, percentages or rates. In those cases the normality assumption does not hold. The LMM can be extended into a generalized linear mixed model (GLMM), which can account for the discrete nature of SCED count data. In this simulation study, we look at the effects of misspecifying an LMM for SCED count data simulated according to a GLMM. We compare the performance of a misspecified LMM and of a GLMM in terms of goodness of fit, fixed effect parameter recovery, type I error rate, and power. Because the LMM and the GLMM do not estimate identical fixed effects, we provide a transformation to compare the fixed effect parameter recovery. The results show that, compared to the GLMM, the LMM has worse performance in terms of goodness of fit and power. Performance in terms of fixed effect parameter recovery is equally good for both models, and in terms of type I error rate the LMM performs better than the GLMM. Finally, we provide some guidelines for applied researchers about aspects to consider when using an LMM for analyzing SCED count data.

It is common for the primary studies in meta-analyses to report multiple effect sizes, generating dependence among them. Hierarchical three-level models have been proposed as a means to deal with this dependency. Sometimes, however, dependency may be due to multiple random factors, and random factors are not necessarily nested, but rather may be crossed. For instance, effect sizes may belong to different studies, and, at the same time, effect sizes might represent the effects on different outcomes. Cross-classified random-effects models (CCREMs) can be used to model this nonhierarchical dependent structure. In this article, we explore by means of a simulation study the performance of CCREMs in comparison with the use of other meta-analytic models and estimation procedures, including the use of three- and two-level models and robust variance estimation. We also evaluated the performance of CCREMs when the underlying data were generated using a multivariate model. The results indicated that, whereas the quality of fixed-effect estimates is unaffected by any misspecification in the model, the standard error estimates of the mean effect size and of the moderator variables' effects, as well as the variance component estimates, are biased under some conditions. Applying CCREMs led to unbiased fixed-effect and variance component estimates, outperforming the other models. Even when a CCREM was not used to generate the data, applying the CCREM yielded sound parameter estimates and inferences.

In Alzheimer's disease, the density and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomography studies using [ 18 F]9.

The synthesis of standardized regression coefficients is still a controversial issue in the field of meta-analysis. The difficulty lies in the fact that the standardized regression coefficients belonging to regression models that include different sets of covariates do not represent the same parameter, and thus their direct combination is meaningless. In the present study, a new approach called concealed correlations meta-analysis is proposed that allows for using the common information that standardized regression coefficients from different regression models contain to improve the precision of a combined focal standardized regression coefficient estimate. The performance of this new approach was compared with that of two other approaches: (1) carrying out separate meta-analyses for standardized regression coefficients from studies that used the same regression model, and (2) performing a meta-regression on the focal standardized regression coefficients while including an indicator variable as a moderator indicating the regression model to which each standardized regression coefficient belongs. The comparison was done through a simulation study. The results showed that, as expected, the proposed approach led to more accurate estimates of the combined standardized regression coefficients under both random- and fixed-effect models.

Purpose: To assess the binding of the PET tracer [ 18 F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology., Methods: The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [ 18 F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [ 18 F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction., Results: Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [ 18 F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [ 18 F]THK5351 scans without partial volume correction revealed similar results., Conclusion: [ 18 F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [ 18 F]THK5351 binding correlates with the severity of clinical impairment.