Theta Signal Transfer from Parietal to Prefrontal Cortex Ignites Conscious Awareness of Implicit Knowledge during Sequence Learning.

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.

The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents.

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

Learning to read may help promote attention by increasing the volume of the left middle frontal gyrus and enhancing its connectivity to the ventral attention network.

Attention and reading are essential skills for successful schooling and in adult life. While previous studies have documented that attention development supports reading acquisition, whether and how learning to read may improve attention among school-age children and the brain structural and functional development that may be involved remain unknown. In this prospective longitudinal study, we examined bidirectional and longitudinal predictions between attention and reading development and the neural mediators of attention and reading development among school-age children using cross-lagged panel modeling. The results showed that better baseline reading performance significantly predicted better attention performance one year later after controlling for baseline attention performance. In contrast, after controlling for baseline reading performance, attention did not significantly predict reading performance one year later, while more attention problems also significantly predicted worse reading performance. Both the increasing gray matter volume of the left middle frontal gyrus and the increasing connectivity between the left middle frontal gyrus and the ventral attention network mediated the above significant longitudinal predictions. This study, directly revealed that reading skills may predict the development of important cognitive functions, such as attention, in school-age children. Therefore, learning to read is not only a challenge for school-age children but is also an important way to optimize attention and brain development.

Dissociating value-based neurocomputation from subsequent selection-related activations in human decision-making.

Human decision-making requires the brain to fulfill neural computation of benefit and risk and therewith a selection between options. It remains unclear how value-based neural computation and subsequent brain activity evolve to achieve a final decision and which process is modulated by irrational factors. We adopted a sequential risk-taking task that asked participants to successively decide whether to open a box with potential reward/punishment in an eight-box trial, or not to open. With time-resolved multivariate pattern analyses, we decoded electroencephalography and magnetoencephalography responses to two successive low- and high-risk boxes before open-box action. Referencing the specificity of decoding-accuracy peak to a first-stage processing completion, we set it as the demarcation and dissociated the neural time course of decision-making into valuation and selection stages. The behavioral hierarchical drift diffusion modeling confirmed different information processing in two stages, that is, the valuation stage was related to the drift rate of evidence accumulation, while the selection stage was related to the nondecision time spent in response-producing. We further observed that medial orbitofrontal cortex participated in the valuation stage, while superior frontal gyrus engaged in the selection stage of irrational open-box decisions. Afterward, we revealed that irrational factors influenced decision-making through the selection stage rather than the valuation stage.

Developmental Sex Differences in Negative Emotion Decision-Making Dynamics: Computational Evidence and Amygdala-Prefrontal Pathways.

Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

High-altitude exposure duration dependent global and regional gray matter volume decrease in healthy immigrants: a cross-sectional study.

BACKGROUND: The correlation between brain injury and high-altitude (HA) exposure duration (Dur_HA) as well as peripheral oxygen saturation (SpO2) remains unclear. PURPOSE: To evaluate the global and regional brain volume differences between HA immigrants and sea-level residents, and the relationship between brain volume with Dur_HA and SpO2. MATERIAL AND METHODS: Structural magnetic resonance imaging (MRI) scans were acquired in 33 healthy male HA immigrants (HA group) and 33 matched sea-level male residents (SL group). Differences in global gray matter volume (GMV), white matter volume (WMV), brain parenchyma volume (BV), total intracranial volume (TIV), and the volume-fraction (the ratio of GMV/TIV, WMV/TIV, BV/TIV) were assessed. Regional gray matter differences were investigated using voxel-based morphology analysis. The volume of clusters with GM loss were calculated as the volume of volume of interest (V_VOI). Student's t-test and partial correlation were adopted for statistic calculation. RESULTS: Compared to the SL group, the HA immigrants had larger WMV (P = 0.015), smaller ratio of GMV/WMV (P = 0.022), and regional gray matter loss in bilateral basal ganglion, limbic system, midbrain, and vermis (cluster size >100 voxels, family-wise error corrected at P = 0.01). The global GMV, BV, and V_VOI confined to vermis had negative correlations with the Dur_HA (r = -0.369, P = 0.049; r = -0.380, P = 0.042; and r = -0.471, P = 0.010. Neither global nor regional brain volume correlated with SpO2. CONCLUSION: Global and regional brain are affected by long-term HA exposure, and global and regional gray matter have a time-dependent volume loss.

Development of the default-mode network during childhood and adolescence: A longitudinal resting-state fMRI study.

The default-mode network (DMN) is a set of functionally connected regions that play crucial roles in internal cognitive processing. Previous resting-state fMRI studies have demonstrated that the intrinsic functional organization of the DMN undergoes remarkable reconfigurations during childhood and adolescence. However, these studies have mainly focused on cross-sectional designs with small sample sizes, limiting the consistency and interpretations of the findings. Here, we used a large sample of longitudinal resting-state fMRI data comprising 305 typically developing children (6-12 years of age at baseline, 491 scans in total) and graph theoretical approaches to delineate the developmental trajectories of the functional architecture of the DMN. For each child, the DMN was constructed according to a prior parcellation with 32 brain nodes. We showed that the overall connectivity increased in strength from childhood to adolescence and became spatially similar to that in the young adult group (N = 61, 18-28 years of age). These increases were primarily located in the midline structures. Global and local network efficiency in the DMN also increased with age, indicating an enhanced capability in parallel information communication within the brain system. Based on the divergent developmental rates of nodal centrality, we identified three subclusters within the DMN, with the fastest rates in the cluster mainly comprising the anterior medial prefrontal cortex and posterior cingulate cortex. Together, our findings highlight the developmental patterns of the functional architecture in the DMN from childhood to adolescence, which has implications for the understanding of network mechanisms underlying the cognitive development of individuals.

Individualized Cortical Parcellation Based on Diffusion MRI Tractography.

The spatial topological properties of cortical regions vary across individuals. Connectivity-based functional and anatomical cortical mapping in individuals will facilitate research on structure-function relationships. However, individual-specific cortical topographic properties derived from anatomical connectivity are less explored than those based on functional connectivity. We aimed to develop a novel individualized anatomical connectivity-based parcellation framework and investigate individual differences in spatial topographic features of cortical regions using diffusion magnetic resonance imaging (dMRI) tractography. Using a high-quality, repeated-session dMRI dataset (42 subjects, 2 sessions per subject), cortical parcels were derived through in vivo anatomical connectivity-based parcellation. These individual-specific parcels demonstrated good within-individual reproducibility and reflected interindividual differences in anatomical brain organization. Connectivity in these individual-specific parcels was significantly more homogeneous than that based on the group atlas. We found that the position, size, and topography of these anatomical parcels were highly variable across individuals and demonstrated nonredundant information about individual differences. Finally, we found that intersubject variability in anatomical connectivity was correlated with the diversity of anatomical connectivity patterns. Overall, we identified cortical parcels that show homogeneous anatomical connectivity patterns. These parcels displayed marked intersubject spatial variability, which may be used in future functional studies to reveal structure-function relationships in the human brain.

The pontine-driven somatic gaze tract contributes to affective processing in humans.

The relevance of subcortical structures for affective processing is not fully understood. Inspired by the gerbil retino-raphe pathway that has been shown to regulate affective behavior and previous human work showing that the pontine region is important for processing emotion, we asked whether well-established tracts in humans traveling between the eye and the brain stem contribute to functions beyond their conventionally understood roles. Here we report neuroimaging findings showing that optic chiasm-brain stem diffusivity predict responses reflecting perceived arousal and valence. Analyses of subsequent task-evoked connectivity further revealed that visual affective processing implicates the brain stem, particularly the pontine region at an early stage of the cascade, projecting to cortico-limbic regions in a feedforward manner. The optimal model implies that all intrinsic connections between the regions of interest are unidirectional and outwards from the pontine region. These findings suggest that affective processing implicates regions outside the cortico-limbic network. The involvement of a phylogenetically older locus in the pons that has consequences in oculomotor control may imply adaptive consequences of affect detection.

Doctor, Teacher, and Stethoscope: Neural Representation of Different Types of Semantic Relations.

Concepts can be related in many ways. They can belong to the same taxonomic category (e.g., "doctor" and "teacher," both in the category of people) or be associated with the same event context (e.g., "doctor" and "stethoscope," both associated with medical scenarios). How are these two major types of semantic relations coded in the brain? We constructed stimuli from three taxonomic categories (people, manmade objects, and locations) and three thematic categories (school, medicine, and sports) and investigated the neural representations of these two dimensions using representational similarity analyses in human participants (10 men and nine women). In specific regions of interest, the left anterior temporal lobe (ATL) and the left temporoparietal junction (TPJ), we found that, whereas both areas had significant effects of taxonomic information, the taxonomic relations had stronger effects in the ATL than in the TPJ ("doctor" and "teacher" closer in ATL neural activity), with the reverse being true for thematic relations ("doctor" and "stethoscope" closer in TPJ neural activity). A whole-brain searchlight analysis revealed that widely distributed regions, mainly in the left hemisphere, represented the taxonomic dimension. Interestingly, the significant effects of the thematic relations were only observed after the taxonomic differences were controlled for in the left TPJ, the right superior lateral occipital cortex, and other frontal, temporal, and parietal regions. In summary, taxonomic grouping is a primary organizational dimension across distributed brain regions, with thematic grouping further embedded within such taxonomic structures.SIGNIFICANCE STATEMENT How are concepts organized in the brain? It is well established that concepts belonging to the same taxonomic categories (e.g., "doctor" and "teacher") share neural representations in specific brain regions. How concepts are associated in other manners (e.g., "doctor" and "stethoscope," which are thematically related) remains poorly understood. We used representational similarity analyses to unravel the neural representations of these different types of semantic relations by testing the same set of words that could be differently grouped by taxonomic categories or by thematic categories. We found that widely distributed brain areas primarily represented taxonomic categories, with the thematic categories further embedded within the taxonomic structure.

Unbiased age-specific structural brain atlases for Chinese pediatric population.

In magnetic resonance (MR) imaging studies of child brain development, structural brain atlases usually serve as important references for the pediatric population, in which individual images are spatially normalized into a common or standard stereotactic space. However, the popular existing pediatric brain atlases (e.g., National Institutes of Health pediatric atlases, NIH-PD) are mostly based on MR images obtained from Caucasian populations and thus are not ideal for the characterization of the brains of Chinese children due to neuroanatomical differences related to genetic and environmental factors. Here, we use an unbiased template construction algorithm to create a set of age-specific Chinese pediatric (CHN-PD) atlases based on high-quality T1-and T2-weighted MR images from 328 cognitively normal Chinese children aged 6-12 years. The CHN-PD brain atlases include asymmetric and symmetric templates, sex-specific templates and tissue probability templates, and contain multiple age-specific templates at one-year intervals. A direct comparison of the CHN-PD and NIH-PD atlases reveals dramatic anatomical differences mainly in the bilateral frontal and parietal regions. After applying the CHN-PD and NIH-PD atlases to two independent Chinese pediatric datasets (N = 114 and N = 71), we find that the CHN-PD atlases result in significantly higher accuracy than the NIH-PD atlases in both predicting "brain age" and guiding brain tissue segmentation. These results suggest that the CHN-PD brain atlases are necessary for studies of the typical and atypical development of the Chinese pediatric population. These CHN-PD atlases have been released on the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) website (https://www.nitrc.org/projects/chn-pd).

Selectively thermal radiation control in long-wavelength infrared with broadband all-dielectric absorber.

Artificial control of the thermal radiation is of growing importance to fundamental science and technological applications, ranging from waste heat recovery to thermophotovoltaics. Nanophotonics has been proven to be an efficient approach to manipulate the radiation. In comparison with structures utilizing planar subwavelength scale lithography, in this paper, we propose a cascaded all-dielectric multilayer structure to selectively manipulate the thermal radiation characteristics in long-wavelength infrared (LWIR). The broadband emissivity in non-atmospheric windows (6.3-7.5 µm) can reach 0.95 and the average absorption rate is below 3% in atmospheric windows (8-14 µm). The multilayer structure is insensitive to the polarization of the incident waves and maintains a good rectangular absorptivity curve even with large oblique incidence angle at 45 degrees. The outstanding properties of the nanostructures promise various applications in infrared sensing and thermal imaging.

Organizational Principles of Abstract Words in the Human Brain.

words constitute nearly half of the human lexicon and are critically associated with human abstract thoughts, yet little is known about how they are represented in the brain. We tested the neural basis of 2 classical cognitive notions of abstract meaning representation: by linguistic contexts and by semantic features. We collected fMRI BOLD responses for 360 abstract words and built theoretical representational models from state-of-the-art corpus-based natural language processing models and behavioral ratings of semantic features. Representational similarity analyses revealed that both linguistic contextual and semantic feature similarity affected the representation of abstract concepts, but in distinct neural levels. The corpus-based similarity was coded in the high-level linguistic processing system, whereas semantic feature information was reflected in distributed brain regions and in the principal component space derived from whole-brain activation patterns. These findings highlight the multidimensional organization and the neural dissociation between linguistic contextual and featural aspects of abstract concepts.

Transformed Neural Pattern Reinstatement during Episodic Memory Retrieval.

Contemporary models of episodic memory posit that remembering involves the reenactment of encoding processes. Although encoding-retrieval similarity has been consistently reported and linked to memory success, the nature of neural pattern reinstatement is poorly understood. Using high-resolution fMRI on human subjects, our results obtained clear evidence for item-specific pattern reinstatement in the frontoparietal cortex, even when the encoding-retrieval pairs shared no perceptual similarity. No item-specific pattern reinstatement was found in the ventral visual cortex. Importantly, the brain regions and voxels carrying item-specific representation differed significantly between encoding and retrieval, and the item specificity for encoding-retrieval similarity was smaller than that for encoding or retrieval, suggesting different nature of representations between encoding and retrieval. Moreover, cross-region representational similarity analysis suggests that the encoded representation in the ventral visual cortex was reinstated in the frontoparietal cortex during retrieval. Together, these results suggest that, in addition to reinstatement of the originally encoded pattern in the brain regions that perform encoding processes, retrieval may also involve the reinstatement of a transformed representation of the encoded information. These results emphasize the constructive nature of memory retrieval that helps to serve important adaptive functions.SIGNIFICANCE STATEMENT Episodic memory enables humans to vividly reexperience past events, yet how this is achieved at the neural level is barely understood. A long-standing hypothesis posits that memory retrieval involves the faithful reinstatement of encoding-related activity. We tested this hypothesis by comparing the neural representations during encoding and retrieval. We found strong pattern reinstatement in the frontoparietal cortex, but not in the ventral visual cortex, that represents visual details. Critically, even within the same brain regions, the nature of representation during retrieval was qualitatively different from that during encoding. These results suggest that memory retrieval is not a faithful replay of past event but rather involves additional constructive processes to serve adaptive functions.

Value of 3D Pseudo-continuous Arterial Spin Labeling Magnetic Resonance Perfusion Imaging in Evaluating Posterior Circulation Ischemia in the Elderly.

Objective To investigate the value of 3D pseudo-continuous arterial spin labeling (3D-pCASL) magnetic resonance perfusion technique in evaluating posterior circulation ischemia (PCI) of the elderly beyond 80 years old and to offer the evidence of PCI of the elderly for clinical diagnosis. Methods Totally 53 male subjects older than 80 years were recruited in this study,including 20 subjects with clinically diagnosed PCI and 33 normal subjects. All the subjects underwent routine brain magnetic resonance imaging and 3D-pCASL sequence on a 3.0T magnetic resonance imaging system with 8 channel brain coil. Two post-labeling delay (PLD) time (PLD=1525 ms and PLD=2525 ms) of 3D-pCASL were used in this study to increase the accuracy of cerebral blood flow (CBF) change of posterior circulation region. We used SPM12 software to measure mean CBF values of bilateral occipital lobes and bilateral cerebellums. Independent sample t-test and rank-sum test were performed to evaluate the difference of CBF changes of anterior circulation and posterior circulation in two groups at two PLD time,the difference of CBF changes of bilateral occipital lobes and bilateral cerebellums in two groups of two PLD time,and the difference of increment of CBF between two PLD interval between two groups. Results In case group,the CBF value of the anterior circulation was significantly higher than that of posterior circulation at both two PLD time points (PLD=1525 ms and PLD=2525 ms)(P=0.000,P=0.000);in control group,the CBF value of the anterior circulation was significantly higher than that of the posterior circulation only at PLD=1525ms (P=0.025). The CBF values at bilateral occipital lobes and bilateral cerebellums at two PLD time points (PLD=1525 ms and PLD=2525 ms) were significantly higher in case group than in control group(P=0.003,P=0.002,P=0.000,P=0.001,P=0.000,P=0.001,P=0.002,P=0.014,respectively). Compared with the control group,the difference was statistically significant in bilateral occipital lobes and cerebellums with a smaller △CBF between two PLD interval in case group (P=0.004,P=0.001,P=0.001,P=0.025). Conclusion Multiple PLD time points need to be used in 3D-pCASL in diagnosing PCI of the elderly because the posterior circulation is slow in these patients. 3D-pCASL technique is sensitive in detecting decreased CBF in posterior circulation and therefore can be used to predict posterior circulation stroke in the elderly.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

BACKGROUND: We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). MATERIAL AND METHODS: A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. RESULTS: Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. CONCLUSIONS: Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways.

Altered topological properties of the cortical motor-related network in patients with subcortical stroke revealed by graph theoretical analysis.

Cerebral neuroplasticity after stroke has been elucidated by functional neuroimaging. However, little is known concerning how topological properties of the cortical motor-related network evolved following subcortical stroke. In the present study, we investigated 24 subcortical stroke patients with only left motor pathway damaged and 24 matched healthy controls. A cortical motor-related network consisting of 20 brain regions remote from the primary lesion was constructed using resting-state functional MRI datasets. We subsequently used graph theoretical approaches to analyze the topological properties of this network in both stroke patients and healthy controls. In addition, we divided the stroke patients into two subgroups according to their outcomes in hand function to explore relationships between topological properties of this network and outcomes in hand function. Although we observed that the cortical motor-related network in both healthy controls and stroke patients exhibited small-world topology, the local efficiency of this network in stroke patients is higher than and global efficiency is lower than those in healthy controls. In addition, striking alterations in the betweenness centrality of regions were found in stroke patients, including the contralesional supplementary motor area, dorsolateral premotor cortex, and anterior inferior cerebellum. Moreover, we observed significant correlations between betweenness centrality of regions and Fugl-Meyer assessment scores. A tendency for the cortical motor-related network to be close to a regular configuration and altered betweenness centrality of regions were demonstrated in patients with subcortical stroke. This study provided insight into functional organization after subcortical stroke from the viewpoint of network topology.

A magnetic nanoparticle stabilized gas containing emulsion for multimodal imaging and triggered drug release.

PURPOSE: To develop a multimodal imaging guided and triggered drug delivery system based on a novel emulsion formulation composed of iron oxide nanoparticles, nanoscopic bubbles, and oil containing drugs. METHODS: Iron oxide paramagnetic nanoparticles were synthesized and modified with surface conjugation of polyethylenimide (PEI) or Bovine Serum Albumin (BSA). Both particles were used to disperse and stabilize oil in water emulsions containing coumarin-6 as the model drug. Sulfur hexafluoride was introduced into the oil phase to form nanoscopic bubbles inside the emulsions. The resulted gas containing emulsions were evaluated for their magnetic resonance (MR) and ultrasound (US) imaging properties. The drug release profile triggered by ultrasound was also examined. RESULTS: We have successfully prepared the highly integrated multi-component emulsion system using the surface modified iron oxide nanoparticles to stabilize the interfaces. The resulted structure had distinctive MR and US imaging properties. Upon application of ultrasound waves, the gas containing emulsion would burst and encapsulated drug could be released. CONCLUSION: The integrated emulsion formulation was multifunctional with paramagnetic, sono-responsive and drug-carrying characteristics, which may have potential applications for disease diagnosis and imaging guided drug release.