-
Neurobiology of Language (Cambridge,... 2024In computational models of reading, written words can be read using print-to-sound and/or print-to-meaning pathways. Neuroimaging data associate dorsal stream regions...
In computational models of reading, written words can be read using print-to-sound and/or print-to-meaning pathways. Neuroimaging data associate dorsal stream regions (left posterior occipitotemporal cortex, intraparietal cortex, dorsal inferior frontal gyrus [dIFG]) with the print-to-sound pathway and ventral stream regions (left anterior fusiform gyrus, middle temporal gyrus) with the print-to-meaning pathway. In 69 typical adults, we investigated whether resting state functional connectivity (RSFC) between the visual word form area (VWFA) and dorsal and ventral regions correlated with phonological (nonword reading, nonword repetition, spoonerisms), lexical-semantic (vocabulary, sensitivity to morpheme units in reading), and general literacy (word reading, spelling) skills. VWFA activity was temporally correlated with activity in both dorsal and ventral reading regions. In pre-registered whole-brain analyses, spoonerisms performance was positively correlated with RSFC between the VWFA and left dorsal regions (dIFG, superior parietal and intraparietal cortex). In exploratory region-of-interest analyses, VWFA-dIFG connectivity was also positively correlated with nonword repetition, spelling, and vocabulary. Connectivity between the VWFA and ventral stream regions was not associated with performance on any behavioural measure, either in whole-brain or region-of-interest analyses. Our results suggest that tasks such as spoonerisms and spellings, which are both complex (i.e., involve multiple subprocesses) and have high between-subject variability, provide greater opportunity for observing resting-state brain-behaviour associations. However, the complexity of these tasks limits the conclusions we can draw about the specific mechanisms that drive these associations. Future research would benefit from constructing latent variables from multiple tasks tapping the same reading subprocess.
PubMed: 38939731
DOI: 10.1162/nol_a_00146 -
Frontiers in Aging Neuroscience 2024At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid...
INTRODUCTION
At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (ε4) in a cholesterol and phospholipid transporter, Apolipoprotein E (), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD.
METHODS
We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis.
RESULTS
Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-β (Aβ) load and tau tangle pathologies.
DISCUSSION
Our studies highlight the critical differences in acyl chain remodeling in brain tissue from carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention.
PubMed: 38938596
DOI: 10.3389/fnagi.2024.1419253 -
Addiction Neuroscience Jun 2024Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more...
Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults ( = 32, =20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: = 16; LS: = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.
PubMed: 38938269
DOI: 10.1016/j.addicn.2024.100156 -
BMC Genomics Jun 2024Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD.
METHODS
Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD.
RESULTS
Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk.
CONCLUSION
We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.
Topics: Gastroesophageal Reflux; Humans; Polymorphism, Single Nucleotide; Smoking; Genome-Wide Association Study; Genetic Predisposition to Disease; Mendelian Randomization Analysis; Genomics; Multiomics
PubMed: 38937676
DOI: 10.1186/s12864-024-10536-3 -
Molecular Biomedicine Jun 2024Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in...
Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.
Topics: Animals; Mice; Fibrosis; Disease Progression; Single-Cell Analysis; Gene Expression Profiling; Renal Insufficiency, Chronic; Mice, Knockout; Nerve Tissue Proteins; Membrane Proteins; Kidney; Transcriptome; Reactive Oxygen Species; Epithelial-Mesenchymal Transition; Disease Models, Animal; Mitochondria
PubMed: 38937317
DOI: 10.1186/s43556-024-00187-x -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales...
Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability.
Topics: Humans; Female; Male; Adult; Magnetic Resonance Imaging; Middle Aged; Young Adult; Mental Recall; Aged; Memory, Episodic; Memory Consolidation; Aged, 80 and over; Brain; Brain Mapping; Time Factors
PubMed: 38937077
DOI: 10.1093/cercor/bhae233 -
Metallomics : Integrated Biometal... Jun 2024Ferric-tannic nanoparticles (FTs) are now considered to be new pharmaceuticals appropriate for the prevention of brain aging and related diseases. We have previously...
Ferric-tannic nanoparticles (FTs) are now considered to be new pharmaceuticals appropriate for the prevention of brain aging and related diseases. We have previously shown that FTs could activate axon guidance pathways and cellular clearance functioning in neuronal cell lines. Herein, we further investigated whether FTs could activate the two coordinated neuronal functions of axon guidance and synaptic function in rat brains and neuronal cell lines. A single intravenous injection of safe dose of FTs has been shown to activate a protein expression of axon attractant Netrin-1 and neurotransmitter receptor GABRA4 in the cerebral cortexes of male Wistar rats. According to RNA-seq with targeted analysis, axon guidance and synapses have been enriched and Ephrin membered genes have been identified as coordinating a network of genes for such processes. In vitro, as expected, FTs are also found to activate axon guidance markers and promote neuronal tubes in neuronal cell lines. At the same time, presynaptic markers (synaptophysin), post-synaptic markers (synapsin), and GABRA4 neurotransmitter receptors have been found to be activated by FTs. Interestingly, synaptophysin has been found to localize along the promoted neuronal tubes, suggesting that enhanced axon guidance is associated with the formation and transportation of pre-synaptic vesicles. Preliminarily, repeated injection of FTs into adult rats every 3 days for 10 times could enhance an expression of synaptophysin in cerebral cortex, as compared to control rat. This work demonstrates that FTs can be used for activating brain function associated with axon guidance and synaptic function.
PubMed: 38936837
DOI: 10.1093/mtomcs/mfae031 -
NeuroImage Jun 2024The extended practice of meditation may reduce the influence of state fatigue by changing neurocognitive processing. However, little is known about the preventive...
INTRODUCTION
The extended practice of meditation may reduce the influence of state fatigue by changing neurocognitive processing. However, little is known about the preventive effects of one-session brief focused attention meditation (FAM) on state fatigue in healthy participants or its potential neural mechanisms. This study examined the preventive effects of one-session brief FAM on state fatigue and its neural correlates using resting-state functional MRI (rsfMRI) measurements.
METHODS
We randomly divided 56 meditation-naïve participants into FAM and control groups. After the first rsfMRI scan, each group performed a 10-minute each condition while wearing a functional near-infrared spectroscopy (fNIRS) device for assessing brain activity. Subsequently, following a second rsfMRI scan, the participants completed a fatigue-inducing task (a Go/NoGo task) for 60 min. We evaluated the temporal changes in the Go/NoGo task performance of participants as an indicator of state fatigue. We then calculated changes in the resting-state functional connectivity (rsFC) of the rsfMRI from before to after each condition and compared them between groups. We also evaluated neural correlates between the changes in rsFC and state fatigue.
RESULTS AND DISCUSSION
The fNIRS measurements indicated differences in brain activity during each condition between the FAM and control groups, showing decreased medial prefrontal cortex activity and decreased functional connectivity between the medial prefrontal cortex and middle frontal gyrus. The control group exhibited a decrement in Go/NoGo task performance over time, whereas the FAM group did not. These results, thus, suggested that FAM could prevent state fatigue. Compared with the control group, the rsFC analysis revealed a significant increase in the connectivity between the left dorsomedial prefrontal cortex and right superior parietal lobule in the FAM group, suggesting a modification of attention regulation by cognitive effort. In the control group, increased connectivity was observed between the bilateral posterior cingulate cortex and left inferior occipital gyrus, which might be associated with poor attention regulation and reduced higher-order cognitive function. Additionally, the change in the rsFC of the control group was related to state fatigue.
CONCLUSION
Our findings suggested that one session of 10-minute FAM could prevent behavioral state fatigue by employing cognitive effort to modify attention regulation as well as suppressing poor attention regulation and reduced higher-order cognitive function.
PubMed: 38936650
DOI: 10.1016/j.neuroimage.2024.120709 -
NeuroImage Jun 2024Time and space form an integral part of every human experience, and for the neuronal representation of these perceptual dimensions, previous studies point to the...
Time and space form an integral part of every human experience, and for the neuronal representation of these perceptual dimensions, previous studies point to the involvement of the right-hemispheric intraparietal sulcus and structures in the medial temporal lobe. Here we used multi-voxel pattern analysis (MVPA) to investigate long-term memory traces for temporal and spatial stimulus features in those areas. Participants were trained on four images associated with short versus long durations and with left versus right locations. Our results demonstrate stable representations of both temporal and spatial information in the right posterior intraparietal sulcus. Building upon previous findings of stable neuronal codes for directly perceived durations and locations, these results show that the reactivation of long-term memory traces for temporal and spatial features can be decoded from neuronal activation patterns in the right parietal cortex.
PubMed: 38936649
DOI: 10.1016/j.neuroimage.2024.120706 -
Neuroscience and Biobehavioral Reviews Jun 2024Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with... (Review)
Review
Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed.
PubMed: 38936563
DOI: 10.1016/j.neubiorev.2024.105779