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Nature Communications May 2024Understanding the functional connectivity between brain regions and its emergent dynamics is a central challenge. Here we present a theory-experiment hybrid approach...
Understanding the functional connectivity between brain regions and its emergent dynamics is a central challenge. Here we present a theory-experiment hybrid approach involving iteration between a minimal computational model and in vivo electrophysiological measurements. Our model not only predicted spontaneous persistent activity (SPA) during Up-Down-State oscillations, but also inactivity (SPI), which has never been reported. These were confirmed in vivo in the membrane potential of neurons, especially from layer 3 of the medial and lateral entorhinal cortices. The data was then used to constrain two free parameters, yielding a unique, experimentally determined model for each neuron. Analytic and computational analysis of the model generated a dozen quantitative predictions about network dynamics, which were all confirmed in vivo to high accuracy. Our technique predicted functional connectivity; e. g. the recurrent excitation is stronger in the medial than lateral entorhinal cortex. This too was confirmed with connectomics data. This technique uncovers how differential cortico-entorhinal dialogue generates SPA and SPI, which could form an energetically efficient working-memory substrate and influence the consolidation of memories during sleep. More broadly, our procedure can reveal the functional connectivity of large networks and a theory of their emergent dynamics.
Topics: Entorhinal Cortex; Animals; Neurons; Models, Neurological; Male; Connectome; Nerve Net; Membrane Potentials; Neural Pathways; Computer Simulation; Mice
PubMed: 38719802
DOI: 10.1038/s41467-024-47617-6 -
Acta Neuropathologica Communications May 2024Neuroinflammation and Alzheimer's disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to...
BACKGROUND
Neuroinflammation and Alzheimer's disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to clarify whether a different pattern of neuroinflammation, such as alteration in microglial and astroglial morphology and distribution, is present in DLB cases with and without AD co-pathology.
METHODS
The morphology and load (% area of immunopositivity) of total (Iba1) and reactive microglia (CD68 and HLA-DR), reactive astrocytes (GFAP) and proteinopathies of alpha-synuclein (KM51/pser129), amyloid-beta (6 F/3D) and p-tau (AT8) were assessed in a cohort of mixed DLB + AD (n = 35), pure DLB (n = 15), pure AD (n = 16) and control (n = 11) donors in limbic and neocortical brain regions using immunostaining, quantitative image analysis and confocal microscopy. Regional and group differences were estimated using a linear mixed model analysis.
RESULTS
Morphologically, reactive and amoeboid microglia were common in mixed DLB + AD, while homeostatic microglia with a small soma and thin processes were observed in pure DLB cases. A higher density of swollen astrocytes was observed in pure AD cases, but not in mixed DLB + AD or pure DLB cases. Mixed DLB + AD had higher CD68-loads in the amygdala and parahippocampal gyrus than pure DLB cases, but did not differ in astrocytic loads. Pure AD showed higher Iba1-loads in the CA1 and CA2, higher CD68-loads in the CA2 and subiculum, and a higher astrocytic load in the CA1-4 and subiculum than mixed DLB + AD cases. In mixed DLB + AD cases, microglial load associated strongly with amyloid-beta (Iba1, CD68 and HLA-DR), and p-tau (CD68 and HLA-DR), and minimally with alpha-synuclein load (CD68). In addition, the highest microglial activity was found in the amygdala and CA2, and astroglial load in the CA4. Confocal microscopy demonstrated co-localization of large amoeboid microglia with neuritic and classic-cored plaques of amyloid-beta and p-tau in mixed DLB + AD cases.
CONCLUSIONS
In conclusion, microglial activation in DLB was largely associated with AD co-pathology, while astrocytic response in DLB was not. In addition, microglial activity was high in limbic regions, with prevalent AD pathology. Our study provides novel insights into the molecular neuropathology of DLB, highlighting the importance of microglial activation in mixed DLB + AD.
Topics: Humans; Lewy Body Disease; Alzheimer Disease; Female; Male; Aged; Aged, 80 and over; Neuroinflammatory Diseases; Microglia; Astrocytes; alpha-Synuclein; tau Proteins; Antigens, CD; Amyloid beta-Peptides; Middle Aged; Antigens, Differentiation, Myelomonocytic; Brain; CD68 Molecule
PubMed: 38715119
DOI: 10.1186/s40478-024-01786-z -
BioRxiv : the Preprint Server For... Apr 2024There are well-established relationships between aging and neurodegenerative changes, and between aging and hearing loss. The goal of this study was to determine how...
INTRODUCTION
There are well-established relationships between aging and neurodegenerative changes, and between aging and hearing loss. The goal of this study was to determine how structural brain aging is influenced by hearing loss.
METHODS
Human Connectome Project Aging (HCP-A) data were analyzed, including T1-weighted MRI and Words in Noise (WIN) thresholds (n=623). Freesurfer extracted gray and white matter volume, and cortical thickness, area, and curvature. Linear regression models targeted (1) interactions between age and WIN threshold and (2) correlations with WIN threshold adjusted for age, both corrected for false discovery rate (p<0.05).
RESULTS
WIN threshold moderated age-related increase in volume in bilateral inferior lateral ventricles, with higher threshold associated with increased age-related ventricle expansion. Age-related deterioration in occipital cortex was also increased with higher WIN thresholds. When controlling for age, high WIN threshold was correlated with reduced cortical thickness in Heschl's gyrus, calcarine sulcus, and other sensory regions, and reduced temporal lobe white matter. Older volunteers with poorer hearing and cognitive scores had the lowest volume in left parahippocampal white matter.
CONCLUSIONS
Preserved hearing abilities in aging associated with a reduction of age-related changes to medial temporal lobe, and preserved hearing at any age associated with preserved cortical tissue in auditory and other sensory regions. Future longitudinal studies are needed to assess the causal nature of these relationships, but these results indicate interventions which preserve hearing function may combat some neurodegenerative changes in aging.
PubMed: 38712119
DOI: 10.1101/2024.04.22.590589 -
Scientific Reports May 2024Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the...
Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer's disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at < 0.1, there were no differences in global and regional SUVR between CU A+ and prodromal AD groups. Regional volume differences between the two groups were observed in the amygdala, hippocampus, entorhinal cortex, insula, parahippocampal gyrus, and inferior temporal and parietal cortices. LASSO logistic regression model showed significant associations between prodromal AD and atrophy in the entorhinal cortex, inferior parietal cortex, both amygdalae, and left hippocampus. The mean SUVR in the right superior parietal cortex (beta coefficient = 0.0172) and its interaction with the regional volume (0.0672) were also selected in the LASSO model. The mean SUVR in the right superior parietal cortex was associated with an increased likelihood of prodromal AD (Odds ratio [OR] 1.602, p = 0.014), particularly in participants with lower regional volume (OR 3.389, p < 0.001). Only regional volume differences, not amyloid deposition, were observed between CU A+ and prodromal AD. The reduced volume in the superior parietal cortex may play a significant role in the progression to prodromal AD through its interaction with amyloid deposition in that region.
Topics: Humans; Alzheimer Disease; Male; Female; Aged; Positron-Emission Tomography; Magnetic Resonance Imaging; Prodromal Symptoms; Brain; Middle Aged; Atrophy; Amyloid beta-Peptides; Cognition; Aged, 80 and over; Amyloid; Aniline Compounds; Stilbenes
PubMed: 38698190
DOI: 10.1038/s41598-024-60843-8 -
Frontiers in Neuroscience 2024Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However,...
INTRODUCTION
Cognitive impairment (CI) is a common complication of end-stage renal disease (ESRD) that is associated with structural and functional changes in the brain. However, whether a joint structural and functional alteration pattern exists that is related to CI in ESRD is unclear.
METHODS
In this study, instead of looking at brain structure and function separately, we aim to investigate the covariant characteristics of both functional and structural aspects. Specifically, we took the fusion analysis approach, namely, multimodal canonical correlation analysis and joint independent component analysis (mCCA+jICA), to jointly study the discriminative features in gray matter volume (GMV) measured by T1-weighted (T1w) MRI, fractional anisotropy (FA) in white matter measured by diffusion MRI, and the amplitude of low-frequency fluctuation (ALFF) measured by blood oxygenation-level-dependent (BOLD) MRI in 78 ESRD patients versus 64 healthy controls (HCs), followed by a mediation effect analysis to explore the relationship between neuroimaging findings, cognitive impairments and uremic toxins.
RESULTS
Two joint group-discriminative independent components (ICs) were found to show covariant abnormalities across FA, GMV, and ALFF (all < 0.05). The most dominant joint IC revealed associative patterns of alterations of GMV (in the precentral gyrus, occipital lobe, temporal lobe, parahippocampal gyrus, and hippocampus), alterations of ALFF (in the precuneus, superior parietal gyrus, and superior occipital gyrus), and of white matter FA (in the corticospinal tract and inferior frontal occipital fasciculus). Another significant IC revealed associative alterations of GMV (in the dorsolateral prefrontal and orbitofrontal cortex) and FA (in the forceps minor). Moreover, the brain changes identified by FA and GMV in the above-mentioned brain regions were found to mediate the negative correlation between serum phosphate and mini-mental state examination (MMSE) scores (all < 0.05).
CONCLUSION
The mCCA+jICA method was demonstrated to be capable of revealing covariant abnormalities across neuronal features of different types in ESRD patients as contrasted to HCs, and joint brain changes may play an important role in mediating the relationship between serum toxins and CIs in ESRD. Our results show the mCCA+jICA fusion analysis approach may provide new insights into similar neurobiological studies.
PubMed: 38686326
DOI: 10.3389/fnins.2024.1374948 -
The American Journal of Psychiatry Jun 2024To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders.
METHODS
A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis.
RESULTS
After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively.
CONCLUSIONS
Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Magnetic Resonance Imaging; Brain; Female; Male; Neuropsychological Tests
PubMed: 38685858
DOI: 10.1176/appi.ajp.20230270 -
Frontiers in Neuroscience 2024Visual fatigue resulting from sustained, high-workload visual activities can significantly impact task performance and general wellbeing. So far, however, little is...
INTRODUCTION
Visual fatigue resulting from sustained, high-workload visual activities can significantly impact task performance and general wellbeing. So far, however, little is known about the underlying brain networks of visual fatigue. This study aimed to identify such potential networks using a unique paradigm involving myopia-correcting lenses known to directly modulate subjectively-perceived fatigue levels.
METHODS
A sample of = 31 myopia participants [right eye-SE: -3.77D (SD: 2.46); left eye-SE: -3.75D (SD: 2.45)] performed a demanding visual search task with varying difficulty levels, both with and without the lenses, while undergoing fMRI scanning. There were a total of 20 trials, after each of which participants rated the perceived difficulty and their subjective visual fatigue level. We used representational similarity analysis to decode brain regions associated with fatigue and difficulty, analyzing their individual and joint decoding pattern.
RESULTS AND DISCUSSION
Behavioral results showed correlations between fatigue and difficulty ratings and above all a significant reduction in fatigue levels when wearing the lenses. Imaging results implicated the cuneus, lingual gyrus, middle occipital gyrus (MOG), and declive for joint fatigue and difficulty decoding. Parts of the lingual gyrus were able to selectively decode perceived difficulty. Importantly, a broader network of visual and higher-level association areas showed exclusive decodability of fatigue (culmen, middle temporal gyrus (MTG), parahippocampal gyrus, precentral gyrus, and precuneus). Our findings enhance our understanding of processing within the context of visual search, attention, and mental workload and for the first time demonstrate that it is possible to decode subjectively-perceived visual fatigue during a challenging task from imaging data. Furthermore, the study underscores the potential of myopia-correcting lenses in investigating and modulating fatigue.
PubMed: 38660218
DOI: 10.3389/fnins.2024.1307688 -
BMC Sports Science, Medicine &... Apr 2024Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise...
Effects of mini-basketball training program on social communication impairments and regional homogeneity of brain functions in preschool children with autism spectrum disorder.
BACKGROUND
Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise has been shown to improve SCI, this finding has not been supported by comprehensive scientific evidence. Existing research has established a strong link between the SCI in children with ASD and abnormalities in regional homogeneity (ReHo). Therefore, investigating the effects of physical exercise on SCI and Reho in patients with ASD may help to elucidate the neurological mechanisms involved.
METHODS
The present study included 30 preschool children diagnosed with ASD, with 15 participants in each group (experimental and control). The experimental group underwent a 12-week mini-basketball training program (MBTP) based on routine behavioral rehabilitation, while the control group only received routine behavioral rehabilitation. The Social Responsiveness Scale-Second Edition (SRS-2) was employed to assess SCI in both groups. Resting-state functional magnetic resonance imaging technology was used to evaluate ReHo in both groups.
RESULTS
After 12-week of MBTP, significant group × time interactions were observed between the experimental and control groups in total SRS-2 scores (F = 14.514, p < 0.001, η = 0.341), as well as in the domains of social cognition (F = 15.620, p < 0.001, η = 0.358), social communication (F = 12.460, p < 0.01, η = 0.308), and autistic mannerisms (F = 9.970, p < 0.01, η = 0.263). No statistical difference was found in the scores for the social awareness subscale and social motivation subscale in the group × time interaction (all p > 0.05). The experimental group exhibited increased ReHo in the right Cerebellum_Crus1 and right parahippocampal gyrus, coupled with decreased ReHo in the left middle frontal gyrus (orbital part), left superior frontal gyrus (dorsolateral), left postcentral gyrus, and right superior parietal gyrus. Furthermore, a decrease in ReHo in the left postcentral gyrus positively correlated with changes in social communication scores in SCI behaviors (p < 0.05).
CONCLUSIONS
Our study underscores the effectiveness of a 12-week MBTP in ameliorating SCI and abnormalities in ReHo among preschool children with ASD.
TRIAL REGISTRATION
The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973; August 5, 2019).
PubMed: 38659073
DOI: 10.1186/s13102-024-00885-7 -
Nature Communications Apr 2024Cognitive maps in the hippocampal-entorhinal system are central for the representation of both spatial and non-spatial relationships. Although this system, especially in...
Cognitive maps in the hippocampal-entorhinal system are central for the representation of both spatial and non-spatial relationships. Although this system, especially in humans, heavily relies on vision, the role of visual experience in shaping the development of cognitive maps remains largely unknown. Here, we test sighted and early blind individuals in both imagined navigation in fMRI and real-world navigation. During imagined navigation, the Human Navigation Network, constituted by frontal, medial temporal, and parietal cortices, is reliably activated in both groups, showing resilience to visual deprivation. However, neural geometry analyses highlight crucial differences between groups. A 60° rotational symmetry, characteristic of a hexagonal grid-like coding, emerges in the entorhinal cortex of sighted but not blind people, who instead show a 90° (4-fold) symmetry, indicative of a square grid. Moreover, higher parietal cortex activity during navigation in blind people correlates with the magnitude of 4-fold symmetry. In sum, early blindness can alter the geometry of entorhinal cognitive maps, possibly as a consequence of higher reliance on parietal egocentric coding during navigation.
Topics: Humans; Blindness; Male; Adult; Magnetic Resonance Imaging; Female; Entorhinal Cortex; Brain Mapping; Parietal Lobe; Middle Aged; Spatial Navigation; Young Adult; Visually Impaired Persons; Cognition; Imagination
PubMed: 38658530
DOI: 10.1038/s41467-024-47747-x -
Journal of Asthma and Allergy 2024Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We...
PURPOSE
Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not.
PATIENTS AND METHODS
We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models.
RESULTS
For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level.
CONCLUSION
We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.
PubMed: 38651018
DOI: 10.2147/JAA.S454807