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BioRxiv : the Preprint Server For... May 2024The cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) is not well characterized. In this study,...
The cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) is not well characterized. In this study, we utilized a single-nucleus RNA sequencing dataset from Dorsolateral Prefrontal Cortex (DLFPC) of 424 donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP) to investigate the effect of 10 VEGF genes ( , and ) on AD endophenotypes. Mean age of death was 89 years, among which 68% were females, and 52% has AD dementia. Negative binomial mixed models were used for differential expression analysis and for association analysis with β-amyloid load, PHF tau tangle density, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated signaling was profiled using CellChat. We discovered prefrontal cortical expression was upregulated in AD brains in both endothelial and microglial cells. Higher expression was also associated with worse cross-sectional global cognitive function, longitudinal cognitive trajectories, and β-amyloid load. Similarly, higher endothelial expression was associated with more β-amyloid load. In contrast to the receptors, showed opposing effects on β-amyloid load whereby higher levels in oligodendrocytes was associated with high amyloid burden, while higher levels in inhibitory neurons was associated with lower amyloid burden. Finally, AD cells showed significant reduction in overall VEGF signaling comparing to those from cognitive normal participants. Our results highlight key changes in VEGF receptor expression in endothelial and microglial cells during AD, and the potential protective role of VEGFB in neurons.
PubMed: 38826287
DOI: 10.1101/2024.04.12.589221 -
Brain Stimulation 2024Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological...
BACKGROUND
Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum.
OBJECTIVE/HYPOTHESIS
Our study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations.
METHODS
We recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS.
RESULTS
Stimulation to DLPFC drove widespread low-frequency increases (3-8 Hz) in frontolimbic cortices and high-frequency decreases (30-110 Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation.
CONCLUSIONS
By combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.
Topics: Humans; Transcranial Magnetic Stimulation; Male; Adult; Female; Middle Aged; Electroencephalography; Electrocorticography; Parietal Lobe; Young Adult; Dorsolateral Prefrontal Cortex; Brain Waves
PubMed: 38821396
DOI: 10.1016/j.brs.2024.05.014 -
Journal of Neuroengineering and... May 2024Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive...
BACKGROUND
Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance.
METHODS
The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power.
RESULTS
We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity.
CONCLUSIONS
These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.
Topics: Humans; Transcranial Direct Current Stimulation; Male; Female; Adult; Inhibition, Psychological; Young Adult; Electroencephalography; Evoked Potentials; Gyrus Cinguli; Reaction Time; Theta Rhythm; Stroop Test; Dorsolateral Prefrontal Cortex
PubMed: 38816860
DOI: 10.1186/s12984-024-01385-y -
Journal of Psychiatry & Neuroscience :... 2024Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine...
BACKGROUND
Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine.
METHODS
We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness.
RESULTS
We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness.
LIMITATIONS
We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine.
CONCLUSION
This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.
Topics: Humans; Ketamine; Male; Female; Adult; Magnetic Resonance Imaging; Substance-Related Disorders; Cerebral Cortex; Young Adult; Brain Cortical Thickness; Middle Aged
PubMed: 38816028
DOI: 10.1503/jpn.230111 -
Frontiers in Psychiatry 2024Transcranial direct current stimulation (tDCS) has emerged as a therapeutic option to mitigate symptoms in individuals with autism spectrum disorder (ASD). Our study...
INTRODUCTION
Transcranial direct current stimulation (tDCS) has emerged as a therapeutic option to mitigate symptoms in individuals with autism spectrum disorder (ASD). Our study investigated the effects of a two-week regimen of tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) in children with ASD, examining changes in rhythmic brain activity and alterations in functional connectivity within key neural networks: the default mode network (DMN), sensorimotor network (SMN), and dorsal attention network (DAN).
METHODS
We enrolled twenty-six children with ASD and assigned them randomly to either an active stimulation group (n=13) or a sham stimulation group (n=13). The active group received tDCS at an intensity of 1mA to the left DLPFC for a combined duration of 10 days. Differences in electrical brain activity were pinpointed using standardized low-resolution brain electromagnetic tomography (sLORETA), while functional connectivity was assessed via lagged phase synchronization.
RESULTS
Compared to the typically developing children, children with ASD exhibited lower current source density across all frequency bands. Post-treatment, the active stimulation group demonstrated a significant increase in both current source density and resting state network connectivity. Such changes were not observed in the sham stimulation group.
CONCLUSION
tDCS targeting the DLPFC may bolster brain functional connectivity in patients with ASD, offering a substantive groundwork for potential clinical applications.
PubMed: 38812483
DOI: 10.3389/fpsyt.2024.1407267 -
The Australian and New Zealand Journal... May 2024Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across... (Review)
Review
Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders.
OBJECTIVE
Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions.
METHODS
A literature search was conducted using various databases with keywords including glutamate, glutamine, schizophrenia, psychosis and proton magnetic resonance spectroscopy. Inclusion criteria were limited to case-control studies that reported glutamatergic metabolite levels in adult patients with a schizophrenia spectrum disorder diagnosis - i.e. first-episode psychosis, schizophrenia, treatment-resistant schizophrenia and/or ultra-treatment-resistant schizophrenia - using proton magnetic resonance spectroscopy at 3 T or above. Pooled study data were synthesized and analysed.
RESULTS
A total of 92 studies met the inclusion criteria, including 2721 healthy controls and 2822 schizophrenia spectrum disorder participants. Glu levels were higher in the basal ganglia, frontal cortex and medial prefrontal of first-episode psychosis participants, contrasting overall lower levels in schizophrenia participants. For Gln, strong differences in metabolite levels were evident in the basal ganglia, dorsolateral prefrontal cortex and frontal cortex, with first-episode psychosis showing significantly higher levels in the basal ganglia. In glutamate + glutamine, higher metabolite levels were found across schizophrenia spectrum disorder groups, particularly in the basal ganglia and dorsolateral prefrontal cortex of treatment-resistant schizophrenia participants. Significant relationships were found between metabolite levels and medication status, clinical measures and methodological variables.
CONCLUSION
The review highlights abnormal glutamatergic metabolite levels throughout schizophrenia spectrum disorders and in specific brain regions. The review underscores the importance of standardized future research assessing glutamatergic metabolites using proton magnetic resonance spectroscopy due to considerable literature heterogeneity.
PubMed: 38812258
DOI: 10.1177/00048674241254216 -
Briefings in Bioinformatics May 2024The advancement of spatial transcriptomics (ST) technology contributes to a more profound comprehension of the spatial properties of gene expression within tissues....
The advancement of spatial transcriptomics (ST) technology contributes to a more profound comprehension of the spatial properties of gene expression within tissues. However, due to challenges of high dimensionality, pronounced noise and dynamic limitations in ST data, the integration of gene expression and spatial information to accurately identify spatial domains remains challenging. This paper proposes a SpaNCMG algorithm for the purpose of achieving precise spatial domain description and localization based on a neighborhood-complementary mixed-view graph convolutional network. The algorithm enables better adaptation to ST data at different resolutions by integrating the local information from KNN and the global structure from r-radius into a complementary neighborhood graph. It also introduces an attention mechanism to achieve adaptive fusion of different reconstructed expressions, and utilizes KPCA method for dimensionality reduction. The application of SpaNCMG on five datasets from four sequencing platforms demonstrates superior performance to eight existing advanced methods. Specifically, the algorithm achieved highest ARI accuracies of 0.63 and 0.52 on the datasets of the human dorsolateral prefrontal cortex and mouse somatosensory cortex, respectively. It accurately identified the spatial locations of marker genes in the mouse olfactory bulb tissue and inferred the biological functions of different regions. When handling larger datasets such as mouse embryos, the SpaNCMG not only identified the main tissue structures but also explored unlabeled domains. Overall, the good generalization ability and scalability of SpaNCMG make it an outstanding tool for understanding tissue structure and disease mechanisms. Our codes are available at https://github.com/ZhihaoSi/SpaNCMG.
Topics: Algorithms; Humans; Animals; Mice; Transcriptome; Gene Expression Profiling; Neural Networks, Computer; Computational Biology; Prefrontal Cortex
PubMed: 38811360
DOI: 10.1093/bib/bbae259 -
General Psychiatry 2024Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response...
BACKGROUND
Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.
AIMS
The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN.
METHODS
In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline.
RESULTS
Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN.
CONCLUSIONS
Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.
PubMed: 38808176
DOI: 10.1136/gpsych-2023-101389 -
Clinical Case Reports Jun 2024We present a case of a single left hemisphere temporal-parietal stroke with subacute global aphasia and severe verbal apraxia and moderate dysphagia. The patient...
We present a case of a single left hemisphere temporal-parietal stroke with subacute global aphasia and severe verbal apraxia and moderate dysphagia. The patient underwent a combined transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) and language stimulation with Virtual Reality Rehabilitation System (VRRS). Patient was treated in a 1-h session, for 5 days a week, for 4 consecutive weeks. After treatment, evident improvements in the comprehension of oral and written language, swallowing abilities, and caregiver burden were detected. Power spectrum analysis of EEG data revealed significant enhancements of , , and waves from baseline to follow-up. These preliminary results seem to confirm the reliability of the tDCS translational application in conjunction with computer-based cognitive treatment for language disorders in a patient with stroke-induced aphasia.
PubMed: 38799514
DOI: 10.1002/ccr3.8928 -
Alpha Psychiatry Jan 2024
PubMed: 38799492
DOI: 10.5152/alphapsychiatry.2024.231485