Frontiers in neuroimagingPub Date : 2024-08-14eCollection Date: 2024-01-01DOI: 10.3389/fnimg.2024.1423770
Niels Schwaderlapp, Enya Paschen, Pierre LeVan, Dominik von Elverfeldt, Carola A Haas
{"title":"Probing hippocampal stimulation in experimental temporal lobe epilepsy with functional MRI.","authors":"Niels Schwaderlapp, Enya Paschen, Pierre LeVan, Dominik von Elverfeldt, Carola A Haas","doi":"10.3389/fnimg.2024.1423770","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1423770","url":null,"abstract":"<p><p>Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10 Hz and demonstrated the effects of different stimulation amplitudes (80-230 μA) and frequencies (1-100 Hz) in epileptic mice. Motivated by recent studies exploring 1 Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1 Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1 Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"3 ","pages":"1423770"},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksandra Tolmacheva, Olga Agranovich, E. Blagovechtchenski
{"title":"The importance of brain mapping for rehabilitation in birth nonprogressive neuromuscular diseases","authors":"Aleksandra Tolmacheva, Olga Agranovich, E. Blagovechtchenski","doi":"10.3389/fnimg.2024.1359491","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1359491","url":null,"abstract":"While motor mapping has been extensively studied in acquired motor conditions, a lack has been observed in terms of research on neurological disorders present since birth, with damage to the spinal cord and peripheral nerves (hence, defined in this study as nonprogressive neuromuscular diseases). Despite an injury at the level below the brain, the subsequent changes in the motor system involve cortical reorganization. In the scientific community, the need for a comprehensive approach targeting the brain is increasingly recognized for greater motor recovery in these patients. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are the most utilized techniques for motor mapping. The knowledge obtained through motor mapping may be used to develop effective individual neuromodulation therapy that helps in functional motor recovery. This brief review compares the results of the brain mapping of a few existing studies in individuals with nonprogressive motor disorders of nonbrain origin present at birth to the brain mapping of individuals with similar acquired motor conditions. The review reveals some particular features in terms of central adaptation in individuals with birth conditions compared to their acquired counterparts, such as the nonsomatotopic presentation of involved muscles in the sensorimotor cortex and nonadjacent cortical areas. This topic is undoubtedly intriguing, justifying further research in the field. This review also discusses the benefits these patients can obtain from neuromodulation therapy addressed to the central nervous system and the importance of individual neurophysiological assessment in designing rehabilitation therapy for children with birth motor disorders.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"26 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141645502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in neuroimagingPub Date : 2024-06-25eCollection Date: 2024-01-01DOI: 10.3389/fnimg.2024.1336887
Mo Shahdloo, Nima Khalighinejad, Luke Priestley, Matthew Rushworth, Mark Chiew
{"title":"Dynamic off-resonance correction improves functional image analysis in fMRI of awake behaving non-human primates.","authors":"Mo Shahdloo, Nima Khalighinejad, Luke Priestley, Matthew Rushworth, Mark Chiew","doi":"10.3389/fnimg.2024.1336887","DOIUrl":"10.3389/fnimg.2024.1336887","url":null,"abstract":"<p><strong>Introduction: </strong>Use of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data.</p><p><strong>Methods: </strong>We correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction.</p><p><strong>Results: </strong>Applying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates.</p><p><strong>Conclusions: </strong>Our results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"3 ","pages":"1336887"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew B. Newberg, N. Wintering, Chloe Hriso, Faezeh Vedaei, Sara Gottfried, Reneita Ross
{"title":"Neuroimaging evaluation of the long term impact of a novel paired meditation practice on brain function","authors":"Andrew B. Newberg, N. Wintering, Chloe Hriso, Faezeh Vedaei, Sara Gottfried, Reneita Ross","doi":"10.3389/fnimg.2024.1368537","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1368537","url":null,"abstract":"A growing number of advanced neuroimaging studies have compared brain structure and function in long term meditators to non-meditators. The goal is to determine if there may be long term effects on the brain from practicing meditation. In this paper, we present new data on the long term effects of a novel meditation practice in which the focus is on clitoral stimulation. The findings from such a study have implications for potential therapeutic uses with regard to various neurological or psychiatric conditions.We evaluated the cerebral glucose metabolism in 40 subjects with an extended history (>1 year of practice, 2–3 times per week) performing the meditation practice called Orgasmic Meditation (OM) and compared their brains to a group of non-meditating healthy controls (N = 19). Both meditation and non-meditation subjects underwent brain PET after injection with 148 to 296 MBq of FDG using a standard imaging protocol. Resting FDG PET scans of the OM group were compared to the resting scans of healthy, non-meditating, controls using statistical parametric mapping.The OM group showed significant differences in metabolic activity at rest compared to the controls. Specifically, there was significantly lower metabolism in select areas of the frontal, temporal, and parietal lobes, as well as the anterior cingulate, insula, and thalamus, in the OM group compared to the controls. In addition, there were notable distinctions between the males and females with the females demonstrating significantly lower metabolism in the thalamus and insula.Overall, these findings suggest that the long term meditation practitioners of OM have different patterns of resting brain metabolism. Since these areas of the brain in which OM practitioners differ from controls are involved in cognition, attention, and emotional regulation, such findings have implications for understanding how this meditation practice might affect practitioners over long periods of time.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":" October","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141364647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in neuroimagingPub Date : 2024-05-09eCollection Date: 2024-01-01DOI: 10.3389/fnimg.2024.1356713
Adam C Searleman, Yajun Ma, Srihari Sampath, Srinath Sampath, Robert Bussell, Eric Y Chang, Lisa Deaton, Andrew M Schumacher, Jiang Du
{"title":"3D inversion recovery ultrashort echo time MRI can detect demyelination in cuprizone-treated mice.","authors":"Adam C Searleman, Yajun Ma, Srihari Sampath, Srinath Sampath, Robert Bussell, Eric Y Chang, Lisa Deaton, Andrew M Schumacher, Jiang Du","doi":"10.3389/fnimg.2024.1356713","DOIUrl":"10.3389/fnimg.2024.1356713","url":null,"abstract":"<p><strong>Purpose: </strong>To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.</p><p><strong>Methods: </strong>Non-aqueous myelin protons have ultrashort T<sub>2</sub>s and are \"invisible\" with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T<sub>2</sub> water signal so that the remaining signal is from the ultrashort T<sub>2</sub> myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (<i>n</i> = 4) or control chow (<i>n</i> = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin.</p><p><strong>Results: </strong>IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content.</p><p><strong>Conclusions: </strong>3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"3 ","pages":"1356713"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in neuroimagingPub Date : 2024-04-30eCollection Date: 2024-01-01DOI: 10.3389/fnimg.2024.1405806
Simon Levinson, Michelle Miller, Ahmed Iftekhar, Monica Justo, Daniel Arriola, Wenxin Wei, Saman Hazany, Josue M Avecillas-Chasin, Taylor P Kuhn, Andreas Horn, Ausaf A Bari
{"title":"Corrigendum: A structural connectivity atlas of limbic brainstem nuclei.","authors":"Simon Levinson, Michelle Miller, Ahmed Iftekhar, Monica Justo, Daniel Arriola, Wenxin Wei, Saman Hazany, Josue M Avecillas-Chasin, Taylor P Kuhn, Andreas Horn, Ausaf A Bari","doi":"10.3389/fnimg.2024.1405806","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1405806","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnimg.2022.1009399.].</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"3 ","pages":"1405806"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction and evaluation of a neurofeedback system using finger tapping and near-infrared spectroscopy","authors":"Shingo Takahashi, Daishi Takahashi, Yuki Kuroiwa, Noriko Sakurai, Naoki Kodama","doi":"10.3389/fnimg.2024.1361513","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1361513","url":null,"abstract":"Neurofeedback using near-infrared spectroscopy (NIRS) has been used in patients with stroke and other patients, but few studies have included older people or patients with cognitive impairment.We constructed a NIRS-based neurofeedback system and used finger tapping to investigate whether neurofeedback can be implemented in older adults while finger tapping and whether brain activity improves in older adults and healthy participants. Our simple neurofeedback system was constructed using a portable wearable optical topography (WOT-HS) device. Brain activity was evaluated in 10 older and 31 healthy young individuals by measuring oxygenated hemoglobin concentration during finger tapping and neurofeedback implementation.During neurofeedback, the concentration of oxygenated hemoglobin increased in the prefrontal regions in both the young and older participants.The results of this study demonstrate the usefulness of neurofeedback using simple NIRS devices for older adults and its potential to mitigate cognitive decline.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"52 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. S. Sanabria Bohórquez, Suzanne Baker, P. Manser, Matteo Tonietto, Christopher Galli, Kristin R. Wildsmith, Yixuan Zou, G. Kerchner, R. Weimer, E. Teng
{"title":"Evaluation of partial volume correction and analysis of longitudinal [18F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models","authors":"S. S. Sanabria Bohórquez, Suzanne Baker, P. Manser, Matteo Tonietto, Christopher Galli, Kristin R. Wildsmith, Yixuan Zou, G. Kerchner, R. Weimer, E. Teng","doi":"10.3389/fnimg.2024.1355402","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1355402","url":null,"abstract":"We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates.The VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability.The results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability.NCT02640092 and NCT03289143.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"29 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140371939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federico Spagnolo, Susanna Gobbi, E. Zsoldos, Manon Edde, Matthias Weigel, C. Granziera, Maxime Descoteaux, M. Barakovic, Stefano Magon
{"title":"Down-sampling in diffusion MRI: a bundle-specific DTI and NODDI study","authors":"Federico Spagnolo, Susanna Gobbi, E. Zsoldos, Manon Edde, Matthias Weigel, C. Granziera, Maxime Descoteaux, M. Barakovic, Stefano Magon","doi":"10.3389/fnimg.2024.1359589","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1359589","url":null,"abstract":"Multi-shell diffusion Magnetic Resonance Imaging (dMRI) data has been widely used to characterise white matter microstructure in several neurodegenerative diseases. The lack of standardised dMRI protocols often implies the acquisition of redundant measurements, resulting in prolonged acquisition times. In this study, we investigate the impact of the number of gradient directions on Diffusion Tensor Imaging (DTI) and on Neurite Orientation Dispersion and Density Imaging (NODDI) metrics.Data from 124 healthy controls collected in three different longitudinal studies were included. Using an in-house algorithm, we reduced the number of gradient directions in each data shell. We estimated DTI and NODDI measures on six white matter bundles clinically relevant for neurodegenerative diseases.Fractional Anisotropy (FA) measures on bundles where data were sampled at the 30% rate, showed a median L1 distance of up to 3.92% and a 95% CI of (1.74, 8.97)% when compared to those obtained at reference sampling. Mean Diffusivity (MD) reached up to 4.31% and a 95% CI of (1.60, 16.98)% on the same premises. At a sampling rate of 50%, we obtained a median of 3.90% and a 95% CI of (1.99, 16.65)% in FA, and 5.49% with a 95% CI of (2.14, 21.68)% in MD. The Intra-Cellular volume fraction (ICvf) median L1 distance was up to 2.83% with a 95% CI of (1.98, 4.82)% at a 30% sampling rate and 3.95% with a 95% CI of (2.39, 7.81)% at a 50% sampling rate. The volume difference of the reconstructed white matter at reference and 50% sampling reached a maximum of (2.09 ± 0.81)%.In conclusion, DTI and NODDI measures reported at reference sampling were comparable to those obtained when the number of dMRI volumes was reduced by up to 30%. Close to reference DTI and NODDI metrics were estimated with a significant reduction in acquisition time using three shells, respectively with: 4 directions at a b value of 700 s/mm2, 14 at 1000 s/mm2, and 32 at 2000 s/mm2. The study revealed aspects that can be important for large-scale clinical studies on bundle-specific diffusion MRI.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"94 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140370844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. H. Magnussen, A. Ettrup, S. Lehel, Dan Peters, A. Dyssegaard, M. S. Thomsen, Jens D. Mikkelsen, G. Knudsen
{"title":"Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig","authors":"J. H. Magnussen, A. Ettrup, S. Lehel, Dan Peters, A. Dyssegaard, M. S. Thomsen, Jens D. Mikkelsen, G. Knudsen","doi":"10.3389/fnimg.2024.1358221","DOIUrl":"https://doi.org/10.3389/fnimg.2024.1358221","url":null,"abstract":"The alpha7 nicotinic acetylcholine receptor (α7-nAChR) has has long been considered a promising therapeutic target for addressing cognitive impairments associated with a spectrum of neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, despite this potential, clinical trials employing α7-nAChR (partial) agonists such as TC-5619 and encenicline (EVP-6124) have fallen short in demonstrating sufficient efficacy. We here investigate the target engagement of TC-5619 and encenicline in the pig brain by use of the α7-nAChR radioligand 11C-NS14492 to characterize binding both with in vitro autoradiography and in vivo occupancy using positron emission tomography (PET). In vitro autoradiography demonstrates significant concentration-dependent binding of 11C-NS14492, and both TC-5619 and encenicline can block this binding. Of particular significance, our in vivo investigations demonstrate that TC-5619 achieves substantial α7-nAChR occupancy, effectively blocking approximately 40% of α7-nAChR binding, whereas encenicline exhibits more limited α7-nAChR occupancy. This study underscores the importance of preclinical PET imaging and target engagement analysis in informing clinical trial strategies, including dosing decisions.","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"21 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140375344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}