Browse Articles

Subthalamic Nucleus Deep Brain Stimulation in the Beta Frequency Range Boosts Cortical Beta Oscillations and Slows Down Movement

Recordings from Parkinson's disease (PD) patients show strong beta-band oscillations (13–35 Hz), which can be modulated by deep brain stimulation (DBS). While high-frequency DBS (>100 Hz) ameliorates motor symptoms and reduces beta activity in the basal ganglia and motor cortex, the effects of low-frequency DBS (<30 Hz) are less clear. Clarifying these effects is relevant for the debate about the role of beta oscillations in motor slowing, which might be causal or epiphenomenal. Here, we investigated how subthalamic nucleus (STN) beta-band DBS affects cortical beta oscillations and motor performance. We recorded the magnetoencephalogram of 14 PD patients (nine males) with DBS implants while on their usual medication. Following a baseline recording (DBS OFF), we applied bipolar DBS at beta frequencies (10, 16, 20, 26, and 30 Hz) via the left electrode in a cyclic fashion, turning stimulation on (5 s) and off (3 s) repeatedly. Cyclic stimulation was applied at rest and during right-hand finger tapping. In the baseline recording, we observed a negative correlation between the strength of hemispheric beta power lateralization and the tap rate. Importantly, beta-band DBS accentuated the lateralization and reduced the tap rate proportionally. The change in lateralization was specific to the alpha/beta range (8–26 Hz), outlasted stimulation, and did not depend on the stimulation frequency, suggesting a remote-induced response rather than entrainment. Our study demonstrates that cortical beta oscillations can be manipulated by STN beta-band DBS. This manipulation has consequences for motor performance, supporting a causal role of beta oscillations.

Molecular profiling of breast cancer methylation pattern in triple negative versus non- triple negative breast cancer

Abstract Epigenetic alterations, especially promotor methylation, have a significant impact on gene expression, molecular subtyping, prognosis, and outcome of breast cancer (BC). The methylation profile was assessed for 22 genes of the BC tissue using the EpiTect Methyl II PCR System in 40 triple-negative BC (TNBC) patients compared to 50 non-TNBC group. The data were corelated with the disease-free (DFS) and overall survival (OS) of the patients. Genes that were differentially hypermethylated in TNBC patients compared to those with non-TNBC included CCND2, CDKN2A, ESR1, CDH1, BRCA1, GSTP, RASSF1, SLIT2, MGMT, PTEN, TP73, and PRDM2. These panel achieved 95% sensitivity, 98% specificity, 97.44% positive predictive value (PPV), 94.23% negative predictive value (NPV), and AUC of 0.993. Hypermethylation of BRCA1, CDH1, CDKN2A, ESR1, GSTP, HIC1, MGMT, PRDM2, PTEN, PYCARDM, RASSF1M, THBS1, and TP73 associated significantly with worse OS and DFS in TNBC cohort. Meanwhile, CCNA1 and CDH1 hypermethylation demonstrated significant associations with poor DFS but did not show significant relationships with OS in TNBC patients. PTGS2 and TNFRSF10C methylation were associated with better DFS and OS rates in TNBC patients. On multivariate Cox regression, CCND2 and PTEN hypermethylation were independent predictors of DFS in the overall BC patients. The hypermethylation of BRCA1 and GSTP were independent predictors of DFS, while PTEN hypermethylation was an independent predictor of OS in the TNBC cohort. The identification of hypermethylated genes, such as BRCA1, CCND2, CDH1, ESR1, GSTP, RASSF1, SLIT2, MGMT, and PTEN may serve as potential biomarkers or therapeutic targets for TNBC.

Policy Complexity Suppresses Dopamine Responses

Limits on information processing capacity impose limits on task performance. We show that male and female mice achieve performance on a perceptual decision task that is near-optimal given their capacity limits, as measured by policy complexity (the mutual information between states and actions). This behavioral profile could be achieved by reinforcement learning with a penalty on high complexity policies, realized through modulation of dopaminergic learning signals. In support of this hypothesis, we find that policy complexity suppresses midbrain dopamine responses to reward outcomes. Furthermore, neural and behavioral reward sensitivity were positively correlated across sessions. Our results suggest that policy compression shapes basic mechanisms of reinforcement learning in the brain.

Risk factors and predictive modeling in a US population with sarcopenia: a propensity score cohort study

Topic modeling analysis of the Allen Human Brain Atlas

Cortical Encoding of Spatial Structure and Semantic Content in 3D Natural Scenes

Our visual system enables us to effortlessly navigate and recognize real-world visual environments. Functional magnetic resonance imaging (fMRI) studies suggest a network of scene-responsive cortical visual areas, but much less is known about the temporal order in which different scene properties are analyzed by the human visual system. In this study, we selected a set of 36 full-color natural scenes that varied in spatial structure and semantic content that our male and female human participants viewed both in 2D and 3D while we recorded magnetoencephalography (MEG) data. MEG enables tracking of cortical activity in humans at millisecond timescale. We compared the representational geometry in the MEG responses with predictions based on the scene stimuli using the representational similarity analysis framework. The representational structure first reflected the spatial structure in the scenes in time window 90–125 ms, followed by the semantic content in time window 140–175 ms after stimulus onset. The 3D stereoscopic viewing of the scenes affected the responses relatively late, from ∼140 ms from stimulus onset. Taken together, our results indicate that the human visual system rapidly encodes a scene's spatial structure and suggest that this information is based on monocular instead of binocular depth cues.

Uterine and body temperament in women with and without polycystic ovary syndrome: a case-control study

Retrieval of an Ethanol-Conditioned Taste Aversion Promotes GABAergic Plasticity in the Anterior Insular Cortex

Blunted sensitivity to ethanol’s aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the anterior insular cortex (aIC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit’s potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic currents onto aIC→BLA projections would be facilitated as a consequence of retrieval of an ethanol-conditioned taste aversion (CTA). Consistent with this hypothesis, frequency of mIPSCs was increased 1 h following retrieval of an ethanol-CTA across cell layers in aIC→BLA projection neurons. This increase in GABAergic plasticity occurred in a circuit-specific, time-limited, and ethanol-CTA retrieval-dependent manner. Additionally, local inhibitory inputs onto layer 2/3 aIC→BLA projection neurons were greater in number and strength following ethanol-CTA. Finally, DREADD-mediated inhibition of aIC parvalbumin-expressing cells blunted the retrieval of ethanol-CTA in male, but not female, mice. Collectively, this work implicates a circuit-specific and memory retrieval-dependent increase in GABAergic tone following retrieval of an ethanol-CTA, thereby advancing our understanding of how the aversive effects of ethanol are encoded in the brain.

N-benzyl-N-methyldecane-1-amine derived from garlic ameliorates UVB-induced photoaging in HaCaT cells and SKH-1 hairless mice

miR-16-5p, miR-21-5p, and miR-155-5p in circulating vesicles as psoriasis biomarkers

Abstract Psoriasis is a chronic skin disorder marked by fast skin cell growth, leading to thick, red, scaly patches. MicroRNAs are small, non-coding RNA molecules that play a crucial role in post-transcriptional gene regulation. This study investigates miR-16-5p, miR-21-5p, and miR-155-5p expression in psoriasis EVs and assesses their biomarker potential, exploring associated target genes and pathways via bioinformatics. A cross-sectional and case-control study included 40 psoriasis patients, with blood samples collected in EDTA tubes. RNA from extracellular vesicles was isolated using Qiagen kits, and miRNAs were quantified via RT-qPCR. Bioinformatic analysis predicted target genes using databases like miRDB and TargetScan. Gene expression data from GEO was processed, and differentially expressed genes were identified. This study assessed miR-16-5p, miR-21-5p, and miR-155-5p expression in psoriasis patients’ circulating vesicles versus controls, finding significantly lower levels in patients. ROC analysis confirmed their diagnostic potential. A positive correlation of miR-16-5p with the Psoriasis Area Severity Index (PASI) suggests severity marker potential. Bioinformatics identified 378 common dysregulated genes, revealing key pathways and gene interactions in psoriasis. A heat map confirmed miRNA-mediated gene suppression in the disease. This study identifies miR-16-5p, miR-21-5p, and miR-155-5p as potential psoriasis biomarkers, in addition to finding significant gene interactions and pathways involved in psoriasis pathophysiology.

Cortex-Specific <i>Tmem169</i> Deficiency Induces Defects in Cortical Neuron Development and Autism-Like Behaviors in Mice

The development of the nervous system is a complex process, with many challenging scientific questions yet to be resolved. Disruptions in brain development are strongly associated with neurodevelopmental disorders, such as intellectual disability and autism. While the genetic basis of autism is well established, the precise pathological mechanisms remain unclear. Variations on chromosome 2q have been linked to autism, yet the specific genes responsible for the disorder have not been identified. This study investigates the role of the transmembrane protein 169 ( TMEM169 ) gene, located on human chromosome 2q35, which has not been previously characterized. Our findings indicate that Tmem169 is highly expressed in the nervous system, and its deletion in the male mouse dorsal forebrain results in neuronal morphological abnormalities and synaptic dysfunction. Notably, Tmem169 -deficient mice, irrespective of sex, display behavioral traits resembling those observed in individuals with autism. These results suggest that Tmem169 interacts with several key neuronal proteins, many of which are implicated in neurodevelopmental diseases. Furthermore, we demonstrate that Tmem169 promotes neuronal process and synapse development through its interaction with Shank3.

Effects of startle on cognitive performance and physiological activity revealed by fNIRS and thermal imaging

Abstract Sudden and threatening stimuli can trigger a startle reflex, a stereotyped physiological response that may lead to a brief cognitive incapacitation. Better understanding this reaction would be beneficial to safety-critical occupational domains. We characterized some physiological correlates of the startle response while participants completed a difficult task (Toulouse N-back task) tapping executive functions. During the task, loud and threatening sounds were presented unpredictably to trigger a startle reflex. Brain activity and facial skin temperature were measured in 34 participants using functional near-infrared spectroscopy (fNIRS) and functional infrared thermal imaging (fITI), respectively. In the high difficulty condition, participants were generally less efficient, but their performance improved slightly following startle in the high difficulty condition. Brain activity in the right prefrontal cortex was also higher following startle, potentially reflecting a compensatory overactivation to sustain performance. Interestingly, higher trait-anxiety was associated with lower task performance, still following startle in the high difficulty condition. Finally, we found a decrease in temperature of the right eye and right cheek as well as an increase in the nose temperature following startle. These results underscore the complexity of startle-induced cognitive and physiological dynamics, which may have implications for occupational settings where managing sudden stressors is crucial.

Voxel-Based Lesion–Symptom Mapping Localizes Residual Visual Function in Hemianopia

Damage to the primary visual cortex (V1) results in visual field deficits on the contralateral side of the world corresponding to the damaged region. Patients with such loss nonetheless show varying residual vision within this apparently blind region, with the neural mechanisms underlying this ability obscured by small study populations. We identified lesions on structural scans from 39 patients (12 female) with hemianopia and occipital lobe damage. We estimated the proportion of damage throughout the visual cortex and correlated this with performance in up to three different tests of residual vision in the blind field. We then performed voxel-based lesion–symptom mapping (VLSM) to determine the precise neural regions associated with residual vision. V1 damage did not show a relationship with residual vision measured with any task, although the extent of damage to V4 and hMT+/V5 both correlated with the ability to detect contrast-modulated stimuli. Indeed, damage to hMT+/V5 severely impacted performance across all three tasks, particularly motion detection. Although hMT+/V5 appeared necessary for residual vision, some patients with intact hMT+/V5 had no residual vision, indicating this area alone was not sufficient. VLSM revealed that damage to the optic radiation laterally was most highly associated with poor residual vision. Thus, VLSM indicates that hMT+/V5 and the optic radiation specifically are critical for residual vision in hemianopia.

Robust fuzzy dynamic integrated environmental-economic-social scheduling considering demand response and user’s satisfaction with electricity under multiple uncertainties

An intelligent network framework for driver distraction monitoring based on RES-SE-CNN

Abstract As the quantity of motor vehicles and drivers experiences a continuous upsurge, the road driving environment has grown progressively more complex. This complexity has led to a concomitant increase in the probability of traffic accidents. Ample research has demonstrated that distracted driving constitutes a primary human - related factor precipitating these accidents. Therefore, the real - time monitoring and issuance of warnings regarding distracted driving behaviors are of paramount significance. In this research, an intelligent driver state monitoring methodology founded on the RES - SE - CNN model architecture is proposed. When compared with three classical models, namely VGG19, DenseNet121, and ResNet50, the experimental outcomes indicate that the RES - SE - CNN model exhibits remarkable performance in the detection of driver distraction. Specifically, it attains a correct recognition rate of 97.28%. The RES - SE - CNN network architecture model is characterized by lower memory occupancy, rendering it more amenable to deployment on vehicle mobile terminals. This study validates the potential application of the intelligent driver distraction monitoring model, which is based on transfer learning, within the actual driving environment.

Partially Observable Markov Models Inferred Using Statistical Tests Reveal Context-Dependent Syllable Transitions in Bengalese Finch Songs

Generative models have diverse applications, including language processing and birdsong analysis. In this study, we demonstrate how a statistical test, designed to prevent overgeneralization in sequence generation, can be used to infer minimal models for the syllable sequences in Bengalese finch songs. We focus on the partially observable Markov model (POMM), which consists of states and the probabilistic transitions between them. Each state is associated with a specific syllable, with the possibility that multiple states may correspond to the same syllable. This characteristic differentiates the POMM from a standard Markov model, where each syllable is linked to a single state. The presence of multiple states for a syllable suggests that transitions between syllables are influenced by the specific contexts in which these transitions occur. We apply this method to analyze the songs of six adult male Bengalese finches, both before and after they were deafened. Our results indicate that auditory feedback plays a crucial role in shaping the context-dependent syllable transitions characteristic of Bengalese finch songs.

Genetic variation and heritability of agronomic traits in a native perennial forage species from drylands: breeding potential of Festuca pallescens

Ghrelin Recruits the Endocannabinoid System to Modulate Food Reward

Ghrelin enhances feeding by activating the growth hormone secretagogue receptor (GHSR). In the brain, GHSRs are expressed in regions responsible for regulating food motivation including the ventral tegmental area (VTA). Endogenous cannabinoids also promote food-seeking behaviors through the cannabinoid receptor-1 (CB-1Rs) in brain regions including the VTA. It is not known, however, if ghrelin and endocannabinoids interact in the VTA to produce these effects. We therefore examined if GHSR and CB-1R interact within the VTA to enhance food motivation. Results show that GHSR and CB-1R mRNA are expressed in the VTA cells in male and female rats and mice, with the GHSR being expressed in dopamine cells and the CB-1R being expressed primarily in nondopaminergic cells with no obvious sex differences. Ghrelin directly activated and increased excitatory tone onto dopamine cells of male and female mice. Male rats lacking fully functional GHSR signaling showed disrupted gene expression of transcripts important for regulating the synthesis, release, and degradation of endocannabinoids and lowered the levels of 2-arachidonoylglycerol (2-AG) within the VTA. Moreover, pharmacological antagonism of VTA CB-1Rs attenuates the orexigenic and appetitive effects of intra-VTA ghrelin in rats and blocks the ability of ghrelin to promote excitatory drive to VTA dopamine neurons. Finally, blocking the breakdown of cannabinoids in the VTA enhances the effects of ghrelin on food motivation. Together, our data show that ghrelin stimulates VTA dopamine cells and ultimately food motivation in part through a mechanism that involves endocannabinoid signaling at the CB-1R.

Immune dysregulation in COVID-19 induced ARDS in kidney transplant recipients revealed by single-cell RNA sequencing

Amyloid-β-Driven Synaptic Deficits Are Mediated by Synaptic Removal of GluA3-Containing AMPA Receptors

The detrimental effects of oligomeric amyloid-β (Aβ) on synapses are considered the leading cause for cognitive deficits in Alzheimer's disease. However, through which mechanism Aβ oligomers impair synaptic structure and function remains unknown. Here, we used electrophysiology and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) imaging on mouse and rat neurons to demonstrate that GluA3 expression in neurons lacking GluA3 is sufficient to resensitize their synapses to the damaging effects of Aβ, indicating that GluA3-containing AMPARs at synapses are necessary and sufficient for Aβ to induce synaptic deficits. We found that Aβ oligomers trigger the endocytosis of GluA3 and promote its translocation toward endolysosomal compartments for degradation. Mechanistically, these Aβ-driven effects critically depend on the PDZ-binding motif of GluA3. A single point mutation in the GluA3 PDZ-binding motif prevented Aβ-driven effects and rendered synapses fully resistant to the effects of Aβ. Correspondingly, proteomics on synaptosome fractions from APP/PS1-transgenic mice revealed a selective reduction of GluA3 at an early age. These findings support a model where the endocytosis and lysosomal degradation of GluA3-containing AMPARs are a critical early step in the cascade of events through which Aβ accumulation causes a loss of synapses.