Cerebral Cortex Research Articles

Distinct Effects of Olanzapine Depot Treatment on Behavior and Muscarinic M1 Receptor Expression in the Triple-Hit Wisket Rat Model of Schizophrenia.

This study aimed to characterize the triple-hit schizophrenia-like model rats (Wisket) by the assessment of (1) behavioral parameters in different test conditions (reward-based Ambitus test and HomeManner system) for a prolonged period, (2) cerebral muscarinic M1 receptor (M1R) expression, and (3) the effects of olanzapine treatment on these parameters. Wistar (control) and Wisket rats were injected for three consecutive weeks with olanzapine depot (100 mg/kg) and spent 4 weeks in large cages with environmental enrichment (HomeManner). The vehicle-treated Wisket rats spent longer time awake with decreased grooming activity compared to controls, without changes in their active social behavior (sniffing, playing, fighting) obtained in HomeManner. Olanzapine treatment decreased most of these parameters, only the passive social interaction (huddling during sleeping) enhanced mostly in the Wisket rats on the injection day, which recovered within 4 days. In the Ambitus test, vehicle-treated Wisket rats showed lower locomotor and exploratory activities and impaired cognition compared to control rats, deteriorating by olanzapine in both groups. In Wisket brain samples, the M1R mRNA expression was significantly lower in the cerebral cortex and elevated in the hippocampus, with no difference in the prefrontal cortex versus control. Olanzapine normalized the hippocampal M1R expression, but enhanced it in the prefrontal cortex. The triple-hit Wisket model rats had impaired behavioral characteristics in both acute reward-based test and undisturbed circumstances investigated for prolonged periods, and altered cerebral M1R expression. Chronic olanzapine treatment resulted deterioration of some parameters in control group, and could restore only few negative signs in model rats.

Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome.

Individuals with Prader Willi syndrome (PWS) often exhibit behavioral difficulties characterized by deficient impulse regulation and obsessive-compulsive features resembling those observed in obsessive-compulsive disorder. The genetic configuration of PWS aligns with molecular and neurophysiological findings suggesting dysfunction in the inhibitory gamma-aminobutyric acid (GABA) interneuron system may contribute to its clinical manifestation. In the cerebral cortex, this dysfunction is expressed as desynchronization of local neural activity. We used functional connectivity MRI to examine potential alterations in the local synchrony of the cerebral cortex in PWS. Whole-brain functional connectivity maps were generated using iso-distance average correlation (IDAC) measures in 22 patients with PWS and 22 control participants. Patients with PWS showed reduced local connectivity (weaker synchrony) in frontal areas, including the orbitofrontal cortex, ventral medial and lateral frontal regions, the anterior cingulate cortex, and sensory areas. The presence of obsessive-compulsive symptoms was significantly associated with the degree of functional structure alteration in part of the orbitofrontal and sensory cortices. In addition, abnormally heightened functional connectivity (stronger synchrony) was identified in the posterior cingulate cortex and the bilateral angular gyri, core components of the default mode network, with distance-dependent effects. Our findings of cortical synchrony alterations indicate a degree of overlap with the anatomy of the alterations previously observed in primary obsessive-compulsive disorder, while also suggesting the implication of GABAergic dysfunction in the pathophysiology of the disorder. Our observations may support the rational development of more specific therapeutic strategies in the treatment of behavioral disinhibition characteristic of PWS.

Deciphering consciousness: The role of corticothalamocortical interactions in general anesthesia.

General anesthesia is administered to millions of individuals each year, however, the precise mechanism by which it induces unconsciousness remains unclear. While some theories suggest that anesthesia shares similarities with natural sleep, targeting sleep-promoting areas and inhibiting arousal nuclei, recent research indicates a more complex process. Emerging evidence highlights the critical role of corticothalamocortical circuits, which are involved in higher cognitive functions, in controlling arousal states and modulating transitions between different conscious states during anesthesia. The administration of general anesthetics disrupts connectivity within these circuits, resulting in a reversible state of unconsciousness. This review elucidates how anesthetics impair corticothalamocortical interactions, thereby affecting the flow of information across various cortical layers and disrupting higher-order cognitive functions while preserving basic sensory processing. Additionally, the role of the prefrontal cortex in regulating arousal through both top-down and bottom-up pathways was examined. These findings highlight the intricate interplay between the cortical and subcortical networks in maintaining and restoring consciousness under anesthesia, offering potential therapeutic targets for enhancing anesthesia management.

Elevation of ganglioside degradation pathway drives GM2 and GM3 within amyloid plaques in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that accounts for two-thirds of all dementia cases, and age is the strongest risk factor. In addition to the amyloid hypothesis, lipid dysregulation is now recognized as a core component of AD pathology. Gangliosides are a class of membrane lipids of the glycosphingolipid family and are enriched in the central nervous system (CNS). Ganglioside dysregulation has been implicated in various neurodegenerative diseases, including AD, but the spatial distribution of ganglioside dysregulation with respect to amyloid-beta (Aβ) deposition is not well understood. To address this gap, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was employed to investigate the age-dependent expression profiles of the A-series ganglioside species GD1a, GM1, GM2, and GM3 in the APP/PS1 transgenic mouse model of AD in which age-dependent amyloid-beta (Aβ) plaques develop. This study utilized a dual-resolution approach in combination with whole-brain imaging for comprehensive detection of ganglioside expression across neuroanatomical regions via high-resolution imaging of the cerebral cortex and hippocampus to investigate plaque-associated ganglioside alterations. The results revealed age-dependent changes in the complex gangliosides GM1 and GD1a across white and gray matter regions in both wildtype and APP/PS1 mice. Significantly greater levels of simple gangliosides GM2 and GM3 were observed in the cortex and dentate gyrus of the hippocampus in transgenic mice at 12 and 18m than in age-matched controls. The accumulation of GM3 colocalized with Aβ plaques in aged APP/PS1 mice and correlated with Hexa gene expression, suggesting that ganglioside degradation is a mechanism for the accumulation of GM3. This work is the first to demonstrate that age-related ganglioside dysregulation is spatiotemporally associated with Aβ plaques using sophisticated MSI and reveals novel mechanistic insights into lipid regulation in AD.

4-amino-3-(phenylselanyl) benzenesulfonamide attenuates intermittent cold stress-induced fibromyalgia in mice: Targeting to the Nrf2-NFκB axis

Stress is widely recognized as the primary environmental factor associated with chronic pain conditions, including fibromyalgia. A recent study demonstrated the potential antinociceptive effects of 4-amino-3-(phenylselanyl) benzenesulfonamide (4-APSB) in acute nociceptive animal models due to its antioxidant and anti-inflammatory properties. However, the efficacy of 4-APSB in managing chronic painful conditions, such as fibromyalgia, has not been explored so far. This study investigated the pharmacological effects of 4-APSB in an experimental model of fibromyalgia induced by intermittent cold stress (ICS). Male and female mice were divided into Control, ICS, 4-APSB, and ICS + 4-APSB. After the ICS, the animals were treated with 4-APSB (1 mg kg−1) or vehicle by the intragastric route until the tenth day. The behavioral tasks were performed on days 5, 8, and 10. The findings showed a negative correlation between paw withdrawal threshold and Nrf2 or NFκB mRNA expression levels caused by ICS exposure. The 4-APSB suppressed the nociceptive signs and a depressive like-phenotype in male and female mice exposed to ICS. 4-APBS normalized the elevated levels of TBARS and the up-regulation of Nrf2 and NFκB expression in the cerebral cortex of ICS-exposed mice. This compound also modulated the oxidative stress in the spinal cord of female mice. The 4-APSB attenuated the inhibition of Na+, K+ − ATPase activity in the central nervous system (CNS) of female mice exposed to ICS. 4-APSB attenuated behavioral and redox imbalance triggered by the ICS model in male and female mice, suggesting its beneficial effects for treating fibromyalgia in both sexes.

Assessment of operator performance during dynamically guided osteotomy and root-end resection in endodontic microsurgery: a cross-sectional in vitro study

ObjectivesTo compare in vitro the magnitude of deviations, task-focused performance, and perspective on instrumentation of two operators with different levels of experience using computer-assisted dynamic navigation (C-ADN) systems during osteotomy/root-end resection (RER) in models mimicking thick bone layers overlying the apices. MethodsEight models with 15 tooth replicas each were assigned equally to two operators (experienced/less experienced). Pre- and post-operative cone-beam computed tomography images were superimposed using a C-ADN software to determine discrepancies between the planned and real trajectory of the trephine bur. Task-focused operator performance and subjective aspects derived from operator's perspective related to C-ADN were also analyzed. Statistical analysis was completed through parametric methods and Chi-square/fisher exact tests. ResultsPearson correlation tests showed positive correlations between the distance from buccal cortical plate to root apex regarding deviation at apex, trephination depth, and visuomotor coordination time. The less experienced operator had significantly greater values of visuomotor coordination time, deviation at buccal entry point and apex, trephination depth, and angular deviation, as well as a significantly higher frequency of apex location failures, poor RER quality, and mishaps in comparison with those of the experienced operator, thus leading to a significantly higher task-focused performance for the experienced operator. Both operators improved the visuomotor task through diverse attempts, acknowledged enhanced situation awareness, surgical procedure quality, and patient safety associated to the use of C-ADN, and reported a positive impact on the developing and maintaining navigational skills. Concerns regarding perceived workload, mental demand, and usability difficulties were reported only by the less experienced operator. ConclusionsDynamically guided osteotomy and RER prepared with trephine burs entail a subset of visuomotor skills requiring a special learning which may vary depending on the operator's experience and the procedure complexity as determined by dentoalveolar anatomy. Likewise, the perceived usability about C-ADN systems increases insofar the complexity of the user interface decreases and upsurge the earlier experience with these systems. Statement of clinical relevanceThis study shows that both the technical characteristics involved in the function of C-ADN systems and the subjective operators' perceptions are critical for the accuracy of task-focused performance during endodontic microsurgery.

The Effect of Disulfiram and N-Acetylcysteine, Potential Compensators for Sulfur Disorders, on Lipopolysaccharide-Induced Neuroinflammation Leading to Memory Impairment and the Metabolism of L-Cysteine Disturbance

Background: The role of sulfur-containing drugs, disulfiram (DSF) and N-acetylcysteine (NAC), in alleviating neuroinflammation is poorly understood. The objective of this study was to examine the effect of DSF and NAC on memory and on the metabolism of L-cysteine and inflammation-related parameters in the cerebral cortex of rats in a model of neuroinflammation induced by the administration of lipopolysaccharide (LPS). Methods: All the treatments were administered intraperitoneally for 10 days (LPS at a dose of 0.5 mg/kg b.w., DSF at a dose of 100 mg/kg b.w, and NAC at a dose of 100 mg/kg b.w.). Behavior was evaluated by the novel object recognition (NOR) test and object location (OL) test, and the level of brain-derived neurotrophic factor (BDNF) was assayed to evaluate neuronal functioning. Cerebral cortex homogenates were tested for hydrogen sulfide (H2S), sulfane sulfur, sulfates, non-protein sulfhydryl groups (NPSH), nitric oxide (NO), and reactive oxygen species (ROS) by biochemical analysis. Results: Neither DSF nor NAC alleviated LPS-induced memory disorders estimated by the NOR test and OL test. The studied compounds also did not affect significantly the levels of BDNF, ROS, NO, H2S, and sulfane sulfur in the cerebral cortex. However, we observed an increase in sulfate concentration in brain tissues after LPS treatment, while DSF and NAC caused an additional increase in sulfate concentration. On the other hand, our study showed that the administration of DSF or NAC together with LPS significantly enhanced the cortical level of NPSH, of which glutathione is the main component. Conclusions: Our study did not confirm the suggested potential of DSF and NAC to correct memory disorders; however, it corroborated the notion that they reduced oxidative stress induced by LPS by increasing the NPSH level. Additionally, our study showed an increase in sulfate concentration in the brain tissues after LPS treatment, which means the upregulation of sulfite and sulfate production in inflammatory conditions.

Brain state-dependent neocortico-hippocampal network dynamics are modulated by postnatal stimuli.

Neurons in the cerebral cortex and hippocampus discharge synchronously in brain state-dependent manner to transfer information. Published studies have highlighted the temporal coordination of neuronal activities between the hippocampus and a neocortical area, however, how the spatial extent of neocortical activity relates to hippocampal activity remains partially unknown. We imaged mesoscopic neocortical activity while recording hippocampal local field potentials in anesthetized and unanesthetized GCaMP-expressing transgenic mice. We found that neocortical activity elevates around hippocampal sharp wave ripples (SWR). SWR-associated neocortical activities occurred predominantly in vision-related regions including visual, retrosplenial and frontal cortex. While pre-SWR neocortical activities were frequently observed in awake and natural sleeping states, post-SWR neocortical activity decreased significantly in the latter. Urethane anesthetized mice also exhibited SWR-correlated calcium elevation, but in longer time scale than observed in natural sleeping mice. During hippocampal theta oscillation states, phase-locked oscillations of calcium activity were observed throughout the entire neocortical areas. In addition, possible environmental effects on neocortico-hippocampal dynamics were assessed in this study by comparing mice reared in ISO (isolated condition) and ENR (enriched environment). In both SWR and theta oscillations, mice reared in ISO exhibited clearer brain state-dependent dynamics than those reared in ENR. Our data demonstrate that the neocortex and hippocampus exhibit heterogeneous activity patterns that characterize brain states, and postnatal experience plays a significant role in modulating these patterns.Significant Statement The hippocampus is a center for memory formation. However, the memory formed in the hippocampus is not stored forever, but gradually transferred into the cerebral cortex synchronized activities between the neocortex and hippocampus has been hypothesized (for hippocampus-independent memory see (Sutherland and Rudy, 1989)). However, spatio-temporal dynamics between hippocampus and whole neocortical areas remains partially unexplored. We measured cortical calcium activities with hippocampal electroencephalogram (EEG) simultaneously and found that the activities of widespread neocortical areas are temporally associated with hippocampal EEG. The neocortico-hippocampal dynamics is primarily regulated by animal awake/sleep state. Even if similar EEG patters were observed, temporal dynamics between the neocortex and hippocampus exhibit distinct patterns between awake and sleep period. In addition, animals' postnatal experience modulates the dynamics.

Bilingualism Is Associated with Significant Structural and Connectivity Alterations in the Thalamus in Adulthood.

Language is a sophisticated cognitive skill that relies on the coordinated activity of cerebral cortex. Acquiring a second language creates intricate modifications in brain connectivity. Although considerable studies have evaluated the impact of second language acquisition on brain networks in adulthood, the results regarding the ultimate form of adaptive plasticity remain inconsistent within the adult population. Furthermore, due to the assumption that subcortical regions are not significantly involved in language-related tasks, the thalamus has rarely been analyzed in relation to other language-relevant cortical regions. Given these limitations, we aimed to evaluate the functional connectivity and volume modifications of thalamic subfields using magnetic resonance imaging (MRI) modalities following the acquisition of a second language. Structural MRI and fMRI data from 51 participants were collected from the OpenNeuro database. The participants were divided into three groups: monolingual (ML), early bilingual (EB), and late bilingual (LB). The EB group consisted of individuals proficient in both English and Spanish, with exposure to these languages before the age of 10 years. The LB group consisted of individuals proficient in both English and Spanish, but with exposure to these languages after the age of 14 years. The ML group included participants proficient only in English. Our results revealed that the ML group exhibited increased functional connectivity in all thalamic subfields (anterior, intralaminar-medial, lateral, ventral, and pulvinar) compared with the EB and LB groups. In addition, a significantly decreased volume of the left suprageniculate nucleus was found in the bilingual groups compared with the ML group. This study provides valuable evidence suggesting that acquiring a second language may be protective against dementia, due to its high plasticity potential, which acts synergistically with cognitive functions to slow the degenerative process.

Disturbed hierarchy and mediation in reward-related circuits in depression.

Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation. Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N=52) and demographically matched healthy controls (N=60). Utilizing existing DBS targets as seeds, we conducted step-wise functional connectivity (sFC) analyses to delineate hierarchical pathways linking to cerebral cortices. Subsequently, the mediation effects of cortical regions on the interaction within reward-related circuits were further explored by constructing mediation models. In both cohorts, sFC analysis revealed two reward-related pathways from the deepest DBS targets to intermediate regions including the thalamus, insula, and anterior cingulate cortex (ACC), then to the superficial cortical cortex including medial frontal cortex, posterior default mode network (pDMN), and right dorsolateral prefrontal cortex (DLPFC). Patients exhibited reduced sFC in bilateral thalamus and medial frontal cortex in short and long steps respectively compared to healthy controls. We also discovered the disappearance of the mediation effects of superficial cortical regions on the interaction between DBS targets and intermediate regions in reward-related pathways in patients with MDD. Our findings support abnormal hierarchical connectivity and mediation effects in reward-related brain regions at different depth levels in MDD, which might elucidate the underlying pathophysiological mechanisms and inspire novel targets for non-invasive interventions.

The functional role of oscillatory dynamics in neocortical circuits: A computational perspective

The dynamics of neuronal systems are characterized by hallmark features such as oscillations and synchrony. However, it has remained unclear whether these characteristics are epiphenomena or are exploited for computation. Due to the challenge of selectively interfering with oscillatory network dynamics in neuronal systems, we simulated recurrent networks of damped harmonic oscillators in which oscillatory activity is enforced in each node, a choice well supported by experimental findings. When trained on standard pattern recognition tasks, these harmonic oscillator recurrent networks (HORNs) outperformed nonoscillatory architectures with respect to learning speed, noise tolerance, and parameter efficiency. HORNs also reproduced a many characteristic features of neuronal systems, such as the cerebral cortex and the hippocampus. In trained HORNs, stimulus-induced interference patterns holistically represent the result of comparing sensory evidence with priors stored in recurrent connection weights, and learning-induced weight changes are compatible with Hebbian principles. Implementing additional features characteristic of natural networks, such as heterogeneous oscillation frequencies, inhomogeneous conduction delays, and network modularity, further enhanced HORN performance without requiring additional parameters. Taken together, our model allows us to give plausible a posteriori explanations for features of natural networks whose computational role has remained elusive. We conclude that neuronal systems are likely to exploit the unique dynamics of recurrent oscillator networks whose computational superiority critically depends on the oscillatory patterning of their nodal dynamics. Implementing the proposed computational principles in analog hardware is expected to enable the design of highly energy-efficient and self-adapting devices that could ideally complement existing digital technologies.

PSYCHOPHYSICAL FEATURES OF THE DEVELOPMENT OF PRESCHOOL CHILDREN WITH SPEECH DISORDERS IN THE CONTEXT OF MUSICAL-CREATIVE AND PHYSICAL EDUCATION

Abstract. The comprehensive and harmonious development of a child is linked to their morphological-functional, physical, somatic, mental, and other individual characteristics. Based on this, we considered it necessary, within the framework of a pedagogical experiment, to analyze how subjectively parents assess their children's speech development. Subsequently, for further analysis of the correctional process technology which effectively forms the basis of dance-cognitive education – thus being constantly perfected and practically applied – we deemed it essential to identify certain features of the musical-creative and physical development of children at the initial stage of their preschool education. Objective: to identify the psychophysical and speech characteristics of children’s development, define the specifics of their musical-creative and physical education, in order to develop a further strategy for conducting classes with elements of dance exercises that address speech correction. Subjects: 87 parents of children aged 4–6 years. To study the parameters of speech development and create a characterization of musical- creative and physical education for children, we used the questionnaire survey method. Analysis of the survey data revealed that, despite parents' evident interest in their child’s speech development, not all of them understand their role in the process of speech formation. It was also identified that at the early stages of development, children’s cognitive interests play a predominant role. The results of the survey allowed us to determine the main strategy for physical education for preschoolers with speech disorders, based on the technology we developed for correcting speech impairments through classes incorporating dance exercises. In this aspect, classes with dance elements can creatively fulfill this need, develop a sense of rhythm, strengthen the skeletal and muscular systems, and stimulate memory, attention, thinking, and imagination. This experience may further assist children in successfully mastering various artistic-creative and sports activities such as choreography, theatre arts, playing musical instruments, gymnastics, etc. Among other benefits, dance-corrective exercises involve the use of both short-term and long-term memory to memorize and reproduce dance figures. These exercises impact the activity of motor neurons in the cerebral cortex, thereby developing motor centers. Constant changes in sequences and rhythms in dance stimulate brain neurons, enhancing the functional flexibility of neural processes. Further research – conduct an analysis of the results of assessing speech and psychophysical development, cognitive functions and dance abilities of preschool children at the initial stage of education.

Organizational Principles of the Primate Cerebral Cortex at the Single-Cell Level.

The primate cerebral cortex, the major organ for cognition, consists of an immense number of neurons. However, the organizational principles governing these neurons remain unclear. By accessing the single-cell spatial transcriptome of over 25 million neuron cells across the entire macaque cortex, it is discovered that the distribution of neurons within cortical layers is highly non-random. Strikingly, over three-quarters of these neurons are located in distinct neuronal clusters. Within these clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory neuron clusters mainly consist of excitatory-excitatory combinations, while inhibitory clusters primarily contain excitatory-inhibitory combinations. Both cluster types have roughly equal numbers of neurons in each layer. Importantly, most excitatory and inhibitory neuron clusters form spatial partnerships, indicating a balanced local neuronal network and correlating with specific functional regions. These organizational principles are conserved across mouse cortical regions. These findings suggest that different brain regions of the cortex may exhibit similar mechanisms at the neuronal population level.

Local cortical structure pattern and genetic links in schizophrenia: An MRI and CRISPR/Cas9 study.

While the etiology of schizophrenia (SZ) remains elusive, its diverse phenotypes suggest the involvement of distinct functional cortical areas, and the heritability of SZ implies the underlying genetic factors. This study aimed to integrate imaging and molecular analyses to elucidate the genetic underpinnings of SZ. We investigated the local cortical structural pattern changes in Brodmann areas (BAs) by calculating the cortical structural pattern index (SPI) using magnetic resonance imaging analysis from 194 individuals with SZ and 330 controls. Significant local structural changes were detected in certain Brodmann areas in symmetric or asymmetric patterns, such as symmetric changes in the BA4 primary motor area and BA23 part of posterior cingulate cortex, and asymmetric changes in the BA13 insula, BA11 inferior orbitofrontal area, and BA 24, and BA 31 cingulate cortex. Following genome-wide association tests, we found genetic variants and SNP-mapped genes and verified the areal preferential expression profiles in the developing human and mouse neocortex. Finally, we performed a loss-of-function analysis using the CRISPR/Cas9 system to investigate the effects of disrupting the SZ-related SNP-mapped Morf4l1, Reep3, or Tmed3 gene on cortical cell fate to understand their roles in generating appropriate composition of cortical neurons. This study outlines a pipeline for identifying local structural changes, associated genetic causes, and potential molecular mechanisms underlying mental disorders. Additionally, these data shed light on establishing a structurally integral cerebral cortex for higher cognitive functions.

Auditory Rhythm Encoding during the Last Trimester of Human Gestation: From Tracking the Basic Beat to Tracking Hierarchical Nested Temporal Structures.

Rhythm perception and synchronization to periodicity hold fundamental neurodevelopmental importance for language acquisition, musical behavior, and social communication. Rhythm is omnipresent in the fetal auditory world and newborns demonstrate sensitivity to auditory rhythmic cues. During the last trimester of gestation, the brain begins to respond to auditory stimulation and to code the auditory environment. When and how during this period do the neural capacities for rhythm processing develop? We conducted a cross-sectional study in 46 neonates (24 male) born between 27 and 35 weeks gestational age (wGA), measuring their neural responses to auditory rhythms with high-density electroencephalography during sleep. We developed measures to evaluate neural synchronization to nested rhythmic periodicities, including the fast isochronous beat and slower metrical (beat grouping) structures. We show that neural synchronization to beat and meter becomes stronger with increasing GA, converging on small phase differences between stimulus and neural responses near term, similar to those observed in adults. Dividing the cohort into subpopulations born before and after 33 wGA revealed that both younger and older groups showed neural synchronization to the fast periodicity related to the isochronous beat, whereas only the older group showed significant neural synchronization to the slower meter frequencies related to beat groupings, suggesting that encoding of nested periodicities arrives during late gestation. Together, our results shed light on the rapid evolution of neural coding of external hierarchical auditory rhythms during the third trimester of gestation, starting from the age when the thalamocortical axons establish the first synapses with the cortical plate.

A Deterministic Model for Harmful Algal Bloom (HAB) Patterns Under Turing’s Instability Perspective

Turing’s instability has been widely introduced to explain the formation of several biological and ecological patterns, such as the skin patterning of fish or animals, wings of butterflies, pigmentation, and labyrinth patterns of the cerebral cortex of mammals. Such a mechanism may occur in the ecosystem due to the differential diffusion dispersal that happen if one of the constituent species results in the activator or the prey, showing a tendency to undergo autocatalytic growth. The diffusion of the constituent species activator is a random mobility function called passive diffusion. If the other species in the system (the predator/inhibitor) disperses sufficiently faster than the activator, then the spatially uniform distribution of species becomes unstable, and the system will settle into a stationary state. This paper introduced Turing’s mechanism in our reaction–taxis–diffusion model to simulate the harmful algal bloom (HAB) pattern. A numerical approach, the Runge–Kutta method, was used to deal with this system of reaction–taxis–diffusion equations, and the findings were qualitatively compared to the aerial patterns obtained by a drone flying over Torment Lake in Nova Scotia (Canada) during the bloom season of September 2023.

Bisdemethoxycurcumin mitigates traumatic brain injury in rats by modulating autophagy and oxidative stress via heat shock protein 90 alpha family class A member 1-mediated nuclear translocation of transcription factor EB.

Bisdemethoxycurcumin (BDMC), the primary active compound found in turmeric, exhibits diverse pharmacological properties. The study aimed to investigate the mechanisms underlying the protective effects of BDMC in traumatic brain injury (TBI). A rat TBI model was established using the Feeney's freefall epidural impact method, followed by BDMC treatment. Rat cortical neuron cells were exposed to hydrogen peroxide (H2O2) to induce oxidative stress and then treated with BDMC. The cells were also pretreated with autophagy inhibitor 3-MA and heat shock protein 90 alpha family class A member 1 (HSP90AA1) inhibitor 17-AAG. Additionally, the experiments also involved treating H2O2-exposed cortical neurons with 17-AAG and silencing HSP90AA1 expression. Co-immunoprecipitation was utilized to verify interactions between HSP90AA1 and transcription factor EB (TFEB), TFEB and nuclear factor erythroid 2 related factor 2 (Nrf2), and the localization of these complexes in the cytoplasm and nucleus. BDMC treatment significantly reduced modified neurological severity scores, brain water content, inflammatory infiltration, oxidative stress, and apoptosis in the cerebral cortex of TBI rats. Additionally, BDMC treatment elevated the expression of Beclin 1 and light chain 3 (LC3) II/LC3 I ratio while decreasing p62 expression. It also promoted TFEB nuclear translocation and increased HSP90AA1 levels in both the cytoplasm and nucleus, along with elevated nuclear Nrf2 expressions in TBI models. In vitro experiments showed decreased malondialdehyde levels, elevated glutathione peroxidase and superoxide dismutase levels upon BDMC treatment, along with repressed cortical neurons apoptosis, elevated Beclin 1 and LC3 II/LC3 I expressions, decreased p62 expressions, reduced cytoplasmic TFEB expression, increased nuclear TFEB and Nrf2 expression, and elevated HSP90AA1 expression in the cytoplasm and nucleus. Mechanistically, BDMC mediated autophagy and oxidative stress by activating HSP90AA1/TFEB/Nrf2 axis. Finally, HSP90AA1 was shown to regulate Nrf2 expression by binding to TFEB in the cellular model. BDMC alleviated TBI in rats by regulating autophagy and oxidative stress through HSP90AA1-mediated nuclear translocation of TFEB.

Fast-Spike Interneurons in Visual Cortical Layer 5: Heterogeneous Response Properties Are Related to Thalamocortical Connectivity.

Layer 4 (L4) of rabbit V1 contains fast-spike GABAergic interneurons (suspected inhibitory interneurons, SINs) that receive potent synaptic input from the LGN and generate fast, local feedforward inhibition. These cells display receptive fields with overlapping ON/OFF subregions, nonlinear spatial summation, very broad orientation/directional tuning, and high spontaneous and visually driven firing rates. Fast-spike interneurons are also found in Layer 5 (L5), which receives a much sparser input from the LGN, but the response properties and thalamocortical connectivity of L5 SINs are relatively unstudied. Here, we study L5 SINs in awake rabbits (both sexes) and compare their response properties with previously studied SINs of L4. We also assess thalamocortical connectivity of L5 SINs, examining cross-correlation of retinotopically aligned LGN-SIN spike trains and L5 SIN responses to electrical stimulation of the LGN. These analyses confirmed that many L5 SINs, like L4 SINs, receive a strong, fast monosynaptic drive from the LGN. Moreover, these LGN-connected L5 SINs had response properties similar to those of L4 SINs and were predominantly found in the upper half of L5. In contrast, L5 SINs with longer synaptic latencies to LGN stimulation displayed (1) sharper orientation tuning, (2) longer visual response latencies, (3) lower spontaneous and (4) visually driven firing rates, and (5) were found in the deeper half of L5. We suggest that the long-latency synaptic responses in such L5 SINs reflect a multisynaptic intracortical pathway that generates a different constellation of response properties than seen in L5 SINs that are driven directly by LGN input.

Effective connectivity predicts distributed neural coding of perceptual decision confidence, uncertainty, and speed

Abstract Decision making is often accompanied by a level of confidence regarding the accuracy of one’s decision. Previous studies have indicated neural activity associated with perceptual decision confidence during sensory stimulus presentation. Choice-based reaction time (RT) has been suggested as an indirect but more objective measure of decision confidence—generally faster RT for higher confidence. However, it is unclear whether choice confidence and RT are mediated by distinct neural pathways, and whether their neural correlates are encoded nonlinearly. Within a perceptual decision-making task, we applied functional magnetic resonance imaging-informed electroencephalography-based effective connectivity analysis via dynamic causal modelling (DCM) on event-related potentials and found the frontoparietal network for fast-vs-slow RT condition to be different from that of high-vs-low confidence rating condition. Furthermore, trial-by-trial DCM analysis predicted cortical layer-based, distributed, and nonlinear coding of RT, confidence or uncertainty. Collectively, our study suggests that decision confidence and speed are instantiated by different dynamical networks distributed across cortical layers.

Spatiotemporal network dynamics and structural correlates in the human cerebral cortex in vitro.

Elucidating human cerebral cortex function is essential for understanding the physiological basis of both healthy and pathological brain states. We obtained extracellular local field potential recordings from cortical slices of neocortical tissue from refractory epilepsy patients. Multi-electrode recordings were combined with histological information, providing a two-dimensional spatiotemporal characterization of human cortical dynamics in control conditions and following modulation of the excitation/inhibition balance. Slices expressed spontaneous rhythmic activity consistent with slow wave activity, comprising alternating active (Up) and silent (Down) states (Up-duration: 0.08±0.03s, Down-duration: 2.62±2.12s, frequency: 0.75±0.39Hz). Up states propagated from deep to superficial layers, with faster propagation speeds than in other species (vertical: 64.6mm/s; horizontal: 65.9mm/s). GABAA blockade progressively transformed the emergent activity into epileptiform discharges, marked by higher firing rates, faster network recruitment and propagation, and infraslow rhythmicity (0.01Hz). This dynamical characterization broadens our understanding of the mechanistic organization of the human cortical network at the micro- and mesoscale.