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Alpha-synuclein preformed fibril-induced aggregation and dopaminergic cell death in cathepsin D overexpression and ZKSCAN3 knockout mice 在cathepsin D过表达和ZKSCAN3基因敲除小鼠体内,α-突触核蛋白预成纤维诱导聚集和多巴胺能细胞死亡
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.18.613763
Toni Mueller, Parker Jeffrey, Yecheng He, Xiaosen Ouyang, David Westbrook, Victor Darley-Usmar, Matthew S Goldberg, Laura Volpicelli-Daley, Jianhua Zhang
{"title":"Alpha-synuclein preformed fibril-induced aggregation and dopaminergic cell death in cathepsin D overexpression and ZKSCAN3 knockout mice","authors":"Toni Mueller, Parker Jeffrey, Yecheng He, Xiaosen Ouyang, David Westbrook, Victor Darley-Usmar, Matthew S Goldberg, Laura Volpicelli-Daley, Jianhua Zhang","doi":"10.1101/2024.09.18.613763","DOIUrl":"https://doi.org/10.1101/2024.09.18.613763","url":null,"abstract":"alpha-synuclein accumulation is recognized as a prominent feature in the majority of Parkinson disease cases and also occurs in a broad range of neurodegenerative disorders including Alzheimer disease. It has been shown that alpha-synuclein can spread from a donor cell to neighboring cells and thus propagate cellular damage, antagonizing the effectiveness of therapies such as transplantation of fetal or iPSC derived dopaminergic cells. As we and others previously have shown, insufficient lysosomal function due to genetic mutations or targeted disruption of cathepsin D can cause alpha-synuclein accumulation. We here investigated whether overexpression of cathepsin D or knockout (KO) of the transcriptional suppressor of lysosomal biogenesis ZKSCAN3 can attenuate propagation of alpha-synuclein aggregation and cell death. We examined dopaminergic neurodegeneration in the substantia nigra using stereology of tyrosine hydroxylase-immunoreactive cells 4 months and 6 months after intrastriatal injection of alpha-synuclein preformed fibrils or monomeric alpha-synuclein control in control, central nervous system (CNS)-cathepsin D overexpressing and CNS-specific ZKSCAN3 KO mice. We also examined pS129-alpha-synuclein aggregates in the substantia nigra, cortex, amygdala and striatum. The extent of dopaminergic neurodegeneration and pS129-alpha-synuclein aggregation in the brains of CNS-specific ZKSCAN3 knockout mice and CNS-cathepsin D overexpressing mice was similar to that observed in wild-type mice. Our results indicate that neither enhancing cathepsin D expression nor disrupting ZKSCAN3 in the CNS is sufficient to attenuate pS129-alpha-synuclein aggregate accumulation or dopaminergic neurodegeneration.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250158","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}
引用次数: 0
The mechanism and consequences of amyloid-β modulating thiamine pyrophosphokinase-1 expression in microglia 淀粉样蛋白-β调节小胶质细胞中硫胺素焦磷酸激酶-1表达的机制及后果
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.18.613405
Xiaoqin Cheng, Ruoqi Zhao, Hongyan Qiu, Peiwen Song, Lanwen Kou, Shaoming Sang, Yingfeng Xia, Wenwen Cai, Boru Jin, Qiang Huang, Peng Yuan, Chunjiu Zhong
{"title":"The mechanism and consequences of amyloid-β modulating thiamine pyrophosphokinase-1 expression in microglia","authors":"Xiaoqin Cheng, Ruoqi Zhao, Hongyan Qiu, Peiwen Song, Lanwen Kou, Shaoming Sang, Yingfeng Xia, Wenwen Cai, Boru Jin, Qiang Huang, Peng Yuan, Chunjiu Zhong","doi":"10.1101/2024.09.18.613405","DOIUrl":"https://doi.org/10.1101/2024.09.18.613405","url":null,"abstract":"Ample studies attribute cognitive decline in Alzheimer's disease to amyloid-β deposition 1-6. However, brain amyloid-β accumulation that saturates years before the manifestation of clinical symptoms is dissociated with cognitive decline of the disease 7. It is unknown how these two processes are mechanistically linked. In this and our accompanied study, we report that thiamine pyrophosphokinase-1 (TPK) deficiency plays essential roles in both processes via distinct mechanisms. Here we describe that diminished microglia Tpk controls the propagation of amyloid-β plaques. In APP/PS1 transgenic mice, microglia showed elevated Tpk expression at 2-month-old, but reduction in a plaque-centric manner at 8-month-old. Interestingly, lipopolysaccharide, but not amyloid-β, induceed Tpk reduction in cultured microglia. Tpk reduction led to microglia dysfunction, showing volatile motility but reduced phagocytosis and weak response to focal tissue injury, with accumulation of intracellular lipid droplets and abnormal mitochrondria. In Alzheimer's disease mice, microglia-specific knockout of Tpk caused diminished plaque coverage, exacerbated plaque burden and synaptic loss. However, increased plaques were not accompanied by the development of neurofibrillary tangles or brain atrophy, in contrast to the phenotype described in our accompanied paper with neuronal Tpk deletion. In conclusion, plaque-induced inflammation reduces Tpk in microglia, selectively exacerbating the spread of amyloid pathology.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"200 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250204","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}
引用次数: 0
Lateralized cerebellar connectivity differentiates auditory pathways in echolocating and non-echolocating whales 小脑侧向连接区分回声定位和非回声定位鲸鱼的听觉通路
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.18.609772
Sophie A Flem, Gregory Berns, Ben Inglis, Dillon Niederhut, Eric Montie, Terrence Deacon, Karla L Miller, Peter Tyack, Peter F Cook
{"title":"Lateralized cerebellar connectivity differentiates auditory pathways in echolocating and non-echolocating whales","authors":"Sophie A Flem, Gregory Berns, Ben Inglis, Dillon Niederhut, Eric Montie, Terrence Deacon, Karla L Miller, Peter Tyack, Peter F Cook","doi":"10.1101/2024.09.18.609772","DOIUrl":"https://doi.org/10.1101/2024.09.18.609772","url":null,"abstract":"We report the first application of diffusion tractography to a mysticete, which was analyzed alongside three odontocete brains, allowing the first direct comparison of strength and laterality of auditory pathways in echolocating and non-echolocating whales. Brains were imaged post-mortem at high resolution with a specialized steady state free precession diffusion sequence optimized for dead tissue. We conducted probabilistic tractography to compare the qualitative features, tract strength, and lateralization of potential ascending and descending auditory paths in the mysticete versus odontocetes. Tracts were seeded in the inferior colliculi (IC), a nexus for ascending auditory information, and the cerebellum, a center for sensorimotor integration. Direct IC to temporal lobe pathways were found in all animals, replicating previous cetacean tractography and suggesting conservation of the primary auditory projection path in the cetacean clade. Additionally, odontocete IC-cerebellum pathways exhibited higher overall tract strength than in the mysticete, suggesting a role as descending acousticomotor tracts supporting the rapid sensorimotor integration demands of echolocation. Further, in the mysticete, contralateral right IC to left cerebellum pathways were 17x stronger than those between left IC and right cerebellum, while in odontocetes, the laterality was reversed, and left IC to right cerebellum pathways were 2-4x stronger than those between right IC and left cerebellum. The stronger left IC-right cerebellum connectivity observed in odontocetes corroborates the theory that odontocetes preferentially echolocate with their right phonic lips, as the right phonic lips are likely innervated by left-cortical motor efferents that integrate with left-cortical auditory afferents in right cerebellum. This interpretation is further supported by the reversed lateralization of IC-cerebellar tracts observed in the non-echolocating mysticete. We also found differences in the specific subregions of cerebellum targeted by the IC, both between the mysticete and odontocetes, and between left and right sides. This study establishes foundational knowledge on mysticete auditory connectivity and extends knowledge on the neural basis of echolocation in odontocetes.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250206","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}
引用次数: 0
The transcriptomic landscape of spinal V1 interneurons reveals a role for En1 in specific elements of motor output 脊髓 V1 中间神经元的转录组图谱揭示了 En1 在特定运动输出要素中的作用
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.18.613279
Alexandra J. Trevisan, Katie Han, Phillip Chapman, Anand S. Kulkarni, Jennifer M. Hinton, Cody Ramirez, Ines Klein, Graziana Gatto, Mariano I. Gabitto, Vilas Menon, Jay B. Bikoff
{"title":"The transcriptomic landscape of spinal V1 interneurons reveals a role for En1 in specific elements of motor output","authors":"Alexandra J. Trevisan, Katie Han, Phillip Chapman, Anand S. Kulkarni, Jennifer M. Hinton, Cody Ramirez, Ines Klein, Graziana Gatto, Mariano I. Gabitto, Vilas Menon, Jay B. Bikoff","doi":"10.1101/2024.09.18.613279","DOIUrl":"https://doi.org/10.1101/2024.09.18.613279","url":null,"abstract":"Neural circuits in the spinal cord are composed of diverse sets of interneurons that play crucial roles in shaping motor output. Despite progress in revealing the cellular architecture of the spinal cord, the extent of cell type heterogeneity within interneuron populations remains unclear. Here, we present a single-nucleus transcriptomic atlas of spinal V1 interneurons across postnatal development. We find that the core molecular taxonomy distinguishing neonatal V1 interneurons perdures into adulthood, suggesting conservation of function across development. Moreover, we identify a key role for En1, a transcription factor that marks the V1 population, in specifying one unique subset of V1-Pou6f2 interneurons. Loss of En1 selectively disrupts the frequency of rhythmic locomotor output but does not disrupt flexion/extension limb movement. Beyond serving as a molecular resource for this neuronal population, our study highlights how deep neuronal profiling provides an entry point for functional studies of specialized cell types in motor output.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250207","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}
引用次数: 0
Is there a ubiquitous spectrolaminar motif of local field potential power across primate neocortex? 灵长类动物新皮层的局部场电位功率是否存在无处不在的谱层图案?
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.18.613490
Chase A Mackey, Katharina Duecker, Samuel A Neymotin, Salvador Dura-Bernal, Saskia Haegens, Annamaria Barczak, Monica N O'Connell, Stephanie Jones, Mingzhou Ding, Avniel S Ghuman, Charles E Schroeder
{"title":"Is there a ubiquitous spectrolaminar motif of local field potential power across primate neocortex?","authors":"Chase A Mackey, Katharina Duecker, Samuel A Neymotin, Salvador Dura-Bernal, Saskia Haegens, Annamaria Barczak, Monica N O'Connell, Stephanie Jones, Mingzhou Ding, Avniel S Ghuman, Charles E Schroeder","doi":"10.1101/2024.09.18.613490","DOIUrl":"https://doi.org/10.1101/2024.09.18.613490","url":null,"abstract":"Mendoza-Halliday, Major et al. 2024 (\"The Paper\") advocates a local field potential (LFP)-based approach to functional identification of cortical layers during \"laminar\" (simultaneous recordings from all cortical layers) multielectrode recordings in nonhuman primates (NHPs). The Paper describes a \"ubiquitous spectrolaminar motif\" in the primate neocortex: 1) 75-150 Hz power peaks in the supragranular layers, 2) 10-19 Hz power peaks in the infragranular layers and 3) the crossing point of their laminar power gradients identifies layer 4 (L4). Identification of L4 is critical in general, but especially for The Paper as the \"motif\" discovery is couched within a framework whose central hypothesis is that gamma activity originates in the supragranular layers and reflects feedforward activity, while alpha-beta activity originates in the infragranular layers and reflects feedback activity. In an impressive scientific effort, The Paper analyzed laminar data from 14 cortical areas in 2 prior macaque studies and compared them to marmoset, mouse and human data to further bolster the canonical nature of the motif. Identification of such canonical principles of brain operation is clearly a topic of broad scientific interest. Similarly, a reliable online method for L4 identification would be of broad scientific value for the rapidly increasing use of laminar recordings using numerous evolving technologies. Despite The Paper's strengths, and its potential for scientific impact, a series of concerns that are fundamental to the analysis and interpretation of laminar activity profile data in general, and local field potential (LFP) signals in particular, led us to question its conclusions. We thus evaluated the generality of The Paper's methods and findings using new sets of data comprised of stimulus-evoked laminar response profiles from primary and higher-order auditory cortices (A1 and belt cortex), and primary visual cortex (V1). The rationale for using these areas as a test bed for new methods is that their laminar anatomy and physiology have already been extensively characterized by prior studies, and there is general agreement across laboratories on key matters like L4 identification. Our analyses indicate that The Paper's findings do to generalize well to any of these cortical areas. In particular, we find The Paper's methods for L4 identification to be unreliable. Moreover, both methodological and statistical concerns, outlined below and in the supplement, question the stated prevalence of the motif in The Paper's published dataset. After summarizing our findings and related broader concerns, we briefly critique the evidence from biophysical modeling studies cited to support The Paper's conclusions. While our findings are at odds with the proposition of a ubiquitous spectrolaminar motif in the primate neocortex, The Paper already has, and will continue to spark debate and further experimentation. Hopefully this countervailing presentation will lead to rob","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250450","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}
引用次数: 0
Brain plasticity for visual words: Elementary school teachers can drive changes in weeks that rival those formed over years 大脑对视觉文字的可塑性:小学教师可推动数周内的变化,这些变化可与多年形成的变化相媲美
bioRxiv - Neuroscience Pub Date : 2024-09-19 DOI: 10.1101/2024.09.17.613570
Fang Wang, Elizabeth Y. Toomarian, Radhika S. Gosavi, Blair Kaneshiro, Anthony M. Norcia, Bruce McCandliss
{"title":"Brain plasticity for visual words: Elementary school teachers can drive changes in weeks that rival those formed over years","authors":"Fang Wang, Elizabeth Y. Toomarian, Radhika S. Gosavi, Blair Kaneshiro, Anthony M. Norcia, Bruce McCandliss","doi":"10.1101/2024.09.17.613570","DOIUrl":"https://doi.org/10.1101/2024.09.17.613570","url":null,"abstract":"This study aims to investigate the impact of vocabulary acquisition through short-term classroom learning and its relation to broader forms of vocabulary learning through long-term exposure in daily life. Through a two week of \"learning sprint\" in collaboration with a local elementary school and EEG-Steady State Visual Evoked Potentials (EEG SSVEP) paradigm, we assessed new vocabulary learning in first and second graders within their pedagogical environment. We then compared the results with the word frequency effect, a well-established phenonmenon that reflects long-term vocabulary learning. After two weeks of classroom instruction, newly acquired words elicited neural responses similar to those of high-frequency words, with the effect significantly correlated with children's phonological decoding skills. Additionally, we successfully replicated the word frequency effect using the SSVEP paradigm for the first time. These findings highlight the potential of the \"learning sprint\" model for conducting neuroscience research in authentic educational settings, thereby fostering a stronger connection between education and neuroscience.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250196","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}
引用次数: 0
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses 分离的基底神经节输出通路与基因不同的神经元亚类相对应
bioRxiv - Neuroscience Pub Date : 2024-09-18 DOI: 10.1101/2024.08.28.610136
Alana Mendelsohn, Laudan Nikoobakht, Jay Bikoff, Rui Costa
{"title":"Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses","authors":"Alana Mendelsohn, Laudan Nikoobakht, Jay Bikoff, Rui Costa","doi":"10.1101/2024.08.28.610136","DOIUrl":"https://doi.org/10.1101/2024.08.28.610136","url":null,"abstract":"The basal ganglia control multiple sensorimotor behaviors though anatomically segregated and topographically organized subcircuits with outputs to specific downstream circuits. However, it is unclear how the anatomical organization of basal ganglia output circuits relates to the molecular diversity of cell types. Here, we demonstrate that the major output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) is comprised of transcriptomically distinct subclasses that reflect its distinct progenitor lineages. We show that these subclasses are topographically organized within SNr, project to distinct targets in the midbrain and hindbrain, and receive inputs from different striatal subregions. Finally, we show that these mouse subclasses are also identifiable in human SNr neurons, suggesting that the genetic organization of SNr is evolutionarily conserved. These findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"191 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250231","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}
引用次数: 0
Interaction between facial expression and color in modulating ERP P3 面部表情和颜色在调节 ERP P3 方面的相互作用
bioRxiv - Neuroscience Pub Date : 2024-09-18 DOI: 10.1101/2024.09.16.612994
Yuya Hasegawa, Hideki Tamura, Shigeki Nakauchi, Tetsuto Minami
{"title":"Interaction between facial expression and color in modulating ERP P3","authors":"Yuya Hasegawa, Hideki Tamura, Shigeki Nakauchi, Tetsuto Minami","doi":"10.1101/2024.09.16.612994","DOIUrl":"https://doi.org/10.1101/2024.09.16.612994","url":null,"abstract":"The relationships between facial expression and color affect human cognition functions such as perception and memory. However, whether these relationships influence attention remains unclear. Additionally, whether facial expressions affect selective attention is unknown; for example, reddish angry faces increase negative social evaluation or emotion intensity, but it is unclear whether selective attention is similarly enhanced. To investigate these questions, we examined whether event-related potentials for faces vary depending on facial expression and color by recording electroencephalography (EEG) data. We conducted an oddball task using stimuli that combined facial expressions (angry, neutral) and facial colors (original, red, green). The participants counted the number of times a rarely appearing target face stimulus appeared among the standard face stimuli. The results indicated that the difference in P3 amplitudes for the target and standard faces depended on the combinations of facial expressions and facial colors; the P3 amplitudes for red angry faces were greater than those for red neutral faces. Additionally, there was no significant main effect or interaction effect of facial expression or facial color on P1 amplitudes for the target, and there were significant main effects of facial expression only on the N170 amplitude. These findings suggest that the intensity of a human's selective attention to facial expressions varies according to the higher-order semantic processing of the relationship between emotion and color rather than simple facial expression or facial color effects individually. Our results support the idea that red color increases the human response to anger from an EEG perspective.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"188 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250230","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}
引用次数: 0
Off-Equilibrium Fluctuation-Dissipation Theorem Paves the Way in Alzheimer's Disease Research 非平衡波动-消散定理为阿尔茨海默病研究铺平道路
bioRxiv - Neuroscience Pub Date : 2024-09-18 DOI: 10.1101/2024.09.15.613131
Gustavo A. Patow, Juan Manuel Monti, Irene Acero-Pous, Sebastian Idesis, Anira Escrichs, Yonatan Sanz Perl, Petra Ritter, Morten L Kringelbach, Gustavo Deco
{"title":"Off-Equilibrium Fluctuation-Dissipation Theorem Paves the Way in Alzheimer's Disease Research","authors":"Gustavo A. Patow, Juan Manuel Monti, Irene Acero-Pous, Sebastian Idesis, Anira Escrichs, Yonatan Sanz Perl, Petra Ritter, Morten L Kringelbach, Gustavo Deco","doi":"10.1101/2024.09.15.613131","DOIUrl":"https://doi.org/10.1101/2024.09.15.613131","url":null,"abstract":"INTRODUCTION:\u0000Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Although traditional methods have provided insights into brain dynamics in AD, they have limitations in capturing non-equilibrium dynamics across disease stages. Recent studies suggest that dynamic functional connectivity in resting-state networks (RSNs) may serve as a biomarker for AD, but the role of deviations from dynamical equilibrium remains underexplored.\u0000OBJECTIVE:\u0000This study applies the off-equilibrium fluctuation-dissipation theorem (FDT) [Monti2024] to analyze brain dynamics in AD, aiming to compare deviations from equilibrium in healthy controls, patients with mild cognitive impairment (MCI), and those with AD. The goal is to identify potential biomarkers for early AD detection and understand disease progression's mechanisms.\u0000METHODS: We employed a model-free approach based on FDT to analyze functional magnetic resonance imaging (fMRI) data, including healthy controls, MCI patients, and AD patients. Deviations from equilibrium in resting-state brain activity were quantified using fMRI scans. In addition, we performed model-based simulations incorporating Amyloid-Beta (ABeta), tau burdens, and Generative Effective Connectivity (GEC) for each subject.\u0000RESULTS:\u0000Our findings show that deviations from equilibrium increase during the MCI stage, indicating hyperexcitability, followed by a significant decline in later stages of AD, reflecting neuronal damage. Model-based simulations incorporating ABeta and tau burdens closely replicated these dynamics, especially in AD patients, highlighting their role in disease progression. Healthy controls exhibited lower deviations, while AD patients showed the most significant disruptions in brain dynamics.\u0000DISCUSSION:\u0000The study demonstrates that the off-equilibrium FDT framework can accurately characterize brain dynamics in AD, providing a potential biomarker for early detection. The increase in non-equilibrium deviations during the MCI stage followed by their decline in AD offers a mechanistic explanation for disease progression. Future research should explore how combining this framework with other dynamic brain measures could further refine diagnostic tools and therapeutic strategies for AD and other neurodegenerative diseases.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"113 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250232","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}
引用次数: 0
Anisotropy of object non-rigidity: High-level perceptual consequences of cortical anisotropy 物体非刚性的各向异性:大脑皮层各向异性的高级感知后果
bioRxiv - Neuroscience Pub Date : 2024-09-18 DOI: 10.1101/2024.09.10.612333
Akihito Maruya, Qasim Zaidi
{"title":"Anisotropy of object non-rigidity: High-level perceptual consequences of cortical anisotropy","authors":"Akihito Maruya, Qasim Zaidi","doi":"10.1101/2024.09.10.612333","DOIUrl":"https://doi.org/10.1101/2024.09.10.612333","url":null,"abstract":"This study presents instances where variations in a complex, higher-level perceptual phenomenon- an anisotropy in object non-rigidity is explained by the distribution of low-level neural properties in the primary visual cortex. Specifically, we examine the visual interpretation of two rigidly connected rotating circular rings. At speeds where observers predominantly perceive rigid rotation of the rings rotating horizontally, observers perceive only non-rigid wobbling when the image is rotated by 90°. Additionally, vertically rotating rings appear narrower and longer compared to their physically identical horizontally rotating counterparts. We show that these perceived shape changes can be decoded from V1 outputs by considering anisotropies in orientation-selective cells. We then empirically demonstrate that even when the vertically rotating ellipses are widened or the horizontally rotating ellipses are elongated so that the shapes match, the perceived difference in non-rigidity is reduced only by a small amount and increased non-rigidity persists in vertical rotations, suggesting that motion mechanisms also play a role. By incorporating cortical anisotropies into optic flow computations, we show that motion gradients for vertical rotations align more with physical non-rigidity, while horizontal rotations align closer to rigidity, indicating that cortical anisotropies contribute to the heightened perception of non-rigidity when orientation shifts from horizontal to vertical. The study underscores the importance of low-level anisotropies in shaping high-level percepts and raises questions about their evolutionary significance, particularly for shape constancy and motion perception.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":"136 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250226","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}
引用次数: 0
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