Frontal Cerebral Cortex Research Articles

Investigating the shared genetic links between hypothyroidism and psychiatric disorders: a large-scale genomewide cross-trait analysis

BackgroundAssociations between thyroid diseases and psychiatric disorders have been mainly described before. However, the genetic mechanism behind hypothyroidism and psychiatric disorders remains unexplained. MethodsWe examined the genetic architecture of hypothyroidism and 8 psychiatric disorders. Firstly, the global and local genetic relationship between the paired traits was explored. Secondly, cross-trait analysis was performed to investigate the genomic loci and genes between psychiatric disorders and hypothyroidism. Thirdly, the significant expression of these genes and the causal relationships were investigated. Lastly, enrichment analysis was conducted on these genes to explore their biological mechanisms. ResultsWe observed significant positive genetic correlations between psychiatric disorders and hypothyroidism. The cross-trait meta-analysis identified 62 shared genetic loci between hypothyroidism and psychiatric disorders. The colocalization analysis additionally revealed 15 potential pleiotropic loci with a posterior probabilities.H4 (PP·H4) value >0.7. We also found 2308 genes shared between both traits, which were highly enriched in biological pathways such as immune cell differentiation and autoimmune diseases, as well as in tissue structures like the frontal cortex and cerebral cortex. Especially, many pleiotropic genes were significantly expressed for multiple pairwise traits, such as BCL11B, RERE, and SUOX. Lastly, the Latent causal variable model (LCV) analysis did not find any causal components in the genetic structure between them. LimitationsThe limitations of this study include that the conclusions were drawn from a European population. ConclusionsThese findings not only deepens our understanding of their biological mechanisms but also has significant implications for the intervention and treatment of these diseases.

Discovery of Potential Drug Targeting Key Genes in Alzheimer's Disease: Insights from Transcriptome Analysis and Molecular Docking.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that presents a significant global health challenge. To explore drugs targeting key genes in AD, R software was used to analyze the data of single nuclei transcriptome from human cerebral frontal cortex in AD, and the differentially expressed genes (DEGs) were screened. Then the gene ontology (GO) analysis, Kyoto gene and genome encyclopedia (KEGG) pathway enrichment and protein-protein interaction (PPI) network were analyzed. The hub genes were calculated by Cytoscape software. Molecular docking and molecular dynamics simulation were used to evaluate and visualize the binding between candidate drugs and key genes. A total of 564 DEGs were screened, and the hub genes were ISG15, STAT1, MX1, IFIT3, IFIT2, RSAD2, IFIT1, IFI44, IFI44L and DDX58. Enrichment terms mainly included response to virus, IFN-γ signaling pathway and virus infection. Diclofenac had good binding effect with IFI44 and IFI44L. Potential drugs may act on key gene targets and then regulate biological pathways such as virus response and IFN-γ-mediated signal pathway, so as to achieve anti-virus, improve immune balance and reduce inflammatory response, and thus play a role in anti-AD.

A cross-tissue transcriptome-wide association study identifies new susceptibility genes for frailty.

Background: Although genome-wide association studies (GWAS) have identified 14 loci associated with frailty index (FI) susceptibility, the underlying causative genes and biological mechanisms remain elusive. Methods: A cross-tissue transcriptome-wide association study (TWAS) was conducted utilizing the Unified Test for Molecular Markers (UTMOST), which integrates GWAS summary statistics from 164,610 individuals of European ancestry and 10,616 Swedish participants, alongside gene expression matrices from the Genotype-Tissue Expression (GTEx) Project. Validation of the significant genes was performed through three distinct methods: FUSION, FOCUS, and Multiple Marker Analysis of Genome-wide Annotation (MAGMA). Exploration of tissue and functional enrichment for FI-associated SNPs was conducted using MAGMA. Conditional and joint analyses, along with fine mapping, were employed to enhance our understanding of FI's genetic architecture. Mendelian randomization was employed to ascertain causal relationships between significant genes and FI, and co-localization analysis was utilized to investigate shared SNPs between significant genes and FI. Results: In this study, two novel susceptibility genes associated with the risk of FI were identified through the application of four TWAS methods. Mendelian randomization demonstrated that HTT may elevate the risk of developing frailty, whereas LRPPRC could offer protection against the onset of frailty. Additionally, co-localization analysis identified a shared SNP between LRPPRC and FI. Tissue enrichment analyses revealed that genomic regions linked to SNPs associated with frailty were predominantly enriched in various brain regions, including the frontal cortex, cerebral cortex, and cerebellar hemispheres. Conditional, combined analyses, and fine mapping collectively identified two genetic regions associated with frailty: 2p21 and 4q16.3. Functional enrichment analyses revealed that the pathways associated with frailty were primarily related to the MHC complex, PD-1 signaling, cognition, inflammatory response to antigenic stimuli, and the production of second messenger molecules. Conclusion: This investigation uncovers two newly identified genes with forecasted expression levels associated with the risk of FI, offering new perspectives on the genetic architecture underlying FI.

Classification of MDD using a Transformer classifier with large-scale multisite resting-state fMRI data.

Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide with high recurrence rate. Identifying MDD patients, particularly those with recurrent episodes with resting-state fMRI, may reveal the relationship between MDD and brain function. We proposed a Transformer-Encoder model, which utilized functional connectivity extracted from large-scale multisite rs-fMRI datasets to classify MDD and HC. The model discarded the Transformer's Decoder part, reducing the model's complexity and decreasing the number of parameters to adapt to the limited sample size and it does not require a complex feature selection process and achieves end-to-end classification. Additionally, our model is suitable for classifying data combined from multiple brain atlases and has an optional unsupervised pre-training module to acquire optimal initial parameters and speed up the training process. The model's performance was tested on a large-scale multisite dataset and identified brain regions affected by MDD using the Grad-CAM method. After conducting five-fold cross-validation, our model achieved an average classification accuracy of 68.61% on a dataset consisting of 1611 samples. For the selected recurrent MDD dataset, the model reached an average classification accuracy of 78.11%. Abnormalities were detected in the frontal gyri and cerebral cortex of MDD patients in both datasets. Furthermore, the identified brain regions in the recurrent MDD dataset generally exhibited a higher contribution to the model's performance.

Open access dataset integrating EEG and fNIRS during Stroop tasks

Conflict monitoring and processing are crucial components of the human cognitive system, with significant implications for daily life and the diagnosis of cognitive disorders. The Stroop task, combined with brain function detection technology, has been widely employed as a classical paradigm for investigating conflict processing. However, there remains a lack of public datasets that integrate Electroencephalogram (EEG) and functional Near-infrared Spectroscopy (fNIRS) to simultaneously record brain activity during a Stroop task. We introduce a dual-modality Stroop task dataset incorporating 34-channel EEG (sampling frequency is 1000 Hz) and 20-channel high temporal resolution fNIRS (sampling frequency is 100 Hz) measurements covering the whole frontal cerebral cortex from 21 participants (9 females/12 males, aged 23.0 ± 2.3 years). Event-related potential analysis of EEG recordings and activation analysis of fNIRS recordings were performed to show the significant Stroop effect. We expected that the data provided would be utilized to investigate multimodal data processing algorithms during cognitive processing.

Treponema denticola Has the Potential to Cause Neurodegeneration in the Midbrain via the Periodontal Route of Infection-Narrative Review.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common example of dementia. The neuropathological features of AD are the abnormal deposition of extracellular amyloid-β (Aβ) and intraneuronal neurofibrillary tangles with hyperphosphorylated tau protein. It is recognized that AD starts in the frontal cerebral cortex, and then it progresses to the entorhinal cortex, the hippocampus, and the rest of the brain. However, some studies on animals suggest that AD could also progress in the reverse order starting from the midbrain and then spreading to the frontal cortex. Spirochetes are neurotrophic: From a peripheral route of infection, they can reach the brain via the midbrain. Their direct and indirect effect via the interaction of their virulence factors and the microglia potentially leads to the host peripheral nerve, the midbrain (especially the locus coeruleus), and cortical damage. On this basis, this review aims to discuss the hypothesis of the ability of Treponema denticola to damage the peripheral axons in the periodontal ligament, to evade the complemental pathway and microglial immune response, to determine the cytoskeletal impairment and therefore causing the axonal transport disruption, an altered mitochondrial migration and the consequent neuronal apoptosis. Further insights about the central neurodegeneration mechanism and Treponema denticola's resistance to the immune response when aggregated in biofilm and its quorum sensing are suggested as a pathogenetic model for the advanced stages of AD.

Motivational self-talk mitigates the harmful impact of mental fatigue on endurance performance

In sports, athletes might train or compete with some degree of mental fatigue that has an impact on performance. The present study investigated the effect of strategic motivational self-talk on endurance performance in mentally fatigued individuals. Twelve healthy men performed three cycling endurance tests at 80% peak power output until exhaustion. Two experimental conditions (mental fatigue [MF] and mental fatigue plus motivational self-talk [MF + M−ST]) and a control condition (CO) were set out. Mental fatigue was induced via 30 min Stroop task; an electroencephalogram of the frontal cerebral cortex was continually monitored. Affective state and perceived exertion were recorded during each session and subjective workload after the endurance exercise trials. Theta band power spectral density was significantly higher in both experimental condition (MF and MF + M−ST) compared to CO, without significant differences between MF and MF + M−ST. Endurance performance was significantly worse in MF (227 ± 63s) than in CO (329 ± 84s). However, motivational self-talk reversed the deleterious effect of MF on endurance performance as in MF + M−ST (368 ± 139s) it was significantly better than MF and not significantly different from CO. Displeasure and perceived exertion scores were similar at the end of exercise and presented similar rate of increase among conditions. Mental demand after exercise was significantly greater in MF than in CO condition. These results suggest that motivational self-talk mitigates the negative effect of MF on endurance performance due to an elevated engagement with the task. Lay summary: This study examined to what extent the deliberate and planned use of cue words to enhance motivation (i.e., motivational self-talk), influenced endurance performance in mentally fatigued individuals. The harmful impact of mental fatigue on endurance performance was mitigated by using motivational self-talk during cycling exercise.

Lifetime caffeine and adolescent nicotine exposure in mice: effects on anxiety-like behavior and reward.

Caffeine consumption occurs throughout life, while nicotine use typically begins during adolescence, the period when caffeine-nicotine epidemiological association begins in earnest. Despite that, few studies in animal models parallel the pattern of coexposure that occurs in humans. Therefore, the neurobehavioral consequences of the association between these drugs remain unclear. Here, we exposed Swiss mice to lifetime caffeine. Caffeine solutions of 0.1 g/L (CAF0.1), 0.3 g/L (CAF0.3), or water (CTRL) were used as the sole liquid source, being offered to progenitors until weaning and, after that, directly to the offspring until the last day of adolescent behavioral evaluation. The open field test was used to evaluate acute effects of nicotine, of lifetime caffeine and of their interaction on locomotion and anxiety-like behavior, while the conditioned place preference test was used to assess the impact of caffeine on nicotine (0.5 mg/Kg, i.p.) reward. Frontal cerebral cortex dopamine content, dopamine turnover, and norepinephrine levels, as well as hippocampal serotonin 1A receptor expression were assessed. CAF0.3 mice exhibited an increase in anxiety-like behavior when compared to CAF0.1 and CTRL ones, but nicotine coexposure mitigated the anxiogenic-like caffeine-induced effect. Distinctively, caffeine had no effect on locomotion and failed to interfere with both nicotine-induced hyperactivity and place preference. There were no significant effects on dopaminergic and serotonergic markers. In conclusion, although caffeine did not affect nicotine reward, considering the strong association between anxiety disorders and tobacco consumption, caffeine-induced anxiety-like behavior advises limiting its consumption during development, including adolescence, as caffeine could be a risk factor to nicotine use.

Neonatal Isoflurane Exposure in Rats Impairs Short-Term Memory, Cell Viability, and Glutamate Uptake in Slices of the Frontal Cerebral Cortex, But Not the Hippocampus, in Adulthood.

Neonatal exposure to general anesthetics has been associated with neurotoxicity and morphologic changes in the developing brain. Isoflurane is a volatile anesthetic widely used in pediatric patients to induce general anesthesia, analgesia, and perioperative sedation. In the present study, we investigated the effects of a single neonatal isoflurane (3% in oxygen, 2h) exposure in rats at postnatal day (PND) 7, in short-term (24h - PND8) and long-term (adulthood) protocols. In PND8, ex vivo analysis of hippocampal and frontal cortex slices evaluated cell viability and susceptibility to in vitro glutamate challenge. In adult rats, behavioral parameters related to anxiety-like behavior, short-term memory, and locomotor activity (PND60-62) and ex vivo analysis of cell viability, membrane permeability, glutamate uptake, and susceptibility to in vitro glutamate challenge in hippocampal and cortical slices from PND65. A single isoflurane (3%, 2h) exposure at PND7 did not acutely alter cell viability in cortical and hippocampal slices of infant rats (PND8) per se and did not alter slice susceptibility to in vitro glutamate challenge. In rat's adulthood, behavioral analysis revealed that the neonatal isoflurane exposure did not alter anxiety-like behavior and locomotor activity (open field and rotarod tests). However, isoflurane exposure impaired short-term memory evaluated in the novel object recognition task. Ex vivo analysis of brain slices showed isoflurane neonatal exposure selectively decreased cell viability and glutamate uptake in cortical slices, but it did not alter hippocampal slice viability or glutamate uptake (PND65). Isoflurane exposure did not alter in vitro glutamate-induced neurotoxicity to slices, and isoflurane exposure caused no significant long-term damage to cell membranes in hippocampal or cortical slices. These findings indicate that a single neonatal isoflurane exposure did not promote acute damage; however, it reduced cortical, but not hippocampal, slice viability and glutamate uptake in the adulthood. Additionally, behavioral analysis showed neonatal isoflurane exposure induces short-term recognition memory impairment, consolidating that neonatal exposure to volatile anesthetics may lead to behavioral impairment in the adulthood, although it may damage brain regions differentially.

There is a topographic organization in human cortico-pontine connectivity.

Of the three largest outputs of the cerebral cortex, two have been extensively studied and mapped. Topographic maps of cortico-thalamic and cortico-striatal functional connectivity in humans are well established. However, for the third largest cerebral output, to the pontine nuclei, which connect the cerebrum to the cerebellum, the existence of such an organized connectivity pattern in humans is unknown. Here, using high-resolution functional MRI and a large sample size, we found a topographically organized pattern of functional connectivity between the human cerebral cortex and pons. Our results indicate a rostral-caudal topography; rostral (frontal) cerebral cortex shows connectivity to the rostral pons, and the more caudal cortical areas (i.e. the sensorimotor cortices) show functional connectivity more caudally in the pons, with the occipital lobe connectivity being most caudal. While prefrontal, sensorimotor and occipital cortices have a connectivity to the medial pontine nuclei, posterior parietal cortex and temporal lobe correlate with lateral pontine nuclei. Topography is sufficiently detailed to identify distinct connectivity for leg, trunk, hand and face areas of the motor cortex. These findings reveal the existence of a topographic organization in human cortico-pontine connectivity and provide the topographic map for future studies of cortico-ponto-cerebellum pathway in a variety of disorders.

Effect of handling on ATP utilization of cerebral Na,K-ATPase in rats with trimethyltin-induced neurodegeneration.

Previously it was shown that for reduction of anxiety and stress of experimental animals, preventive handling seems to be one of the most effective methods. The present study was oriented on Na,K-ATPase, a key enzyme for maintaining proper concentrations of intracellular sodium and potassium ions. Malfunction of this enzyme has an essential role in the development of neurodegenerative diseases. It is known that this enzyme requires approximately 50% of the energy available to the brain. Therefore in the present study utilization of the energy source ATP by Na,K-ATPase in the frontal cerebral cortex, using the method of enzyme kinetics was investigated. As a model of neurodegeneration treatment with trimethyltin (TMT) was applied. Daily handling (10min/day) of healthy rats and rats suffering neurodegeneration induced by administration of TMT in a dose of (7.5mg/kg), at postnatal days 60-102 altered the expression of catalytic subunits of Na,K-ATPase as well as kinetic properties of this enzyme in the frontal cerebral cortex of adult male Wistar rats. In addition to the previously published beneficial effect on spatial memory, daily treatment of rats was accompanied by improved maintenance of sodium homeostasis in the frontal cortex. The key system responsible for this process, Na,K-ATPase, was able to utilize better the energy substrate ATP. In rats, manipulation of TMT-induced neurodegeneration promoted the expression of the α2 isoform of the enzyme, which is typical for glial cells. In healthy rats, manipulation was followed by increased expression of the α3 subunit, which is typical of neurons.

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-α) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-α, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. LAY SUMMARY: ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment.

Effects of maternal diazinon exposure on frontal cerebral cortical development in mouse embryo

Background Diazinon including organophosphate (OP) that is widely used in agriculture and animal husbandry industry and the risk of human infection with the toxin and their toxicity. Methods Pregnant balb/c mice (30–35 g) were randomly divided into five groups of five: the control group (no intervention), two sham groups (emulsifier 0.52, and 5.2 liters/volume). From the seventh to the eighteenth day of pregnancy, two experimental groups received diazinon inhaled 1.3 (EXP1) and 13 liters/volume (EXP2) for 40 min every other day, respectively. On the 18th day of pregnancy, the animals were killed and their embryos were removed to appraisal the growth of fetus and development of the frontal cortex. A computer-assisted morphometric quantitative images analysis were performed on the frontal cerebral cortex (FCC) including cortical plate (CP), intermediate zone (IZ) and matrix (proliferative) zone (MZ) of the mouse embryos. Findings The average of crown-rump length and weight of the embryos in the experimental groups were increased without any significant difference. The mean fetal FCC thickness in the EXP2 group was significantly reduced compared to the control group, CP thickness was remarkably increased in fetuses exposed to diazinon. Comparing the mean thickness of MZ and IZ in EXP groups with the sham and control groups indicated a significant decrease. The positive K-67 cells in the FCC of the EXP2 group were significantly reduced. Discussion Exposing diazinon during pregnancy can reduce brain development and would be neurotoxic to the developing brain and can lead to behavioral changes in the offspring.

Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease.

The beneficial effects of drugs that act via nicotinic acetylcholine receptors (nAChRs) on Parkinson's disease (PD) symptomatology may explain the negative correlation between cigarette smoking and risk of this neurological condition. Varenicline, an α4β2 nAChR partial agonist approved for smoking cessation treatments, could be valuable for PD treatment. Here, we investigated varenicline effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model. From postnatal day (PN) 90 to PN119, male C57BL/6 mice were exposed daily to varenicline (2 mg/kg) by gavage. After that, MPTP was injected (30 mg/kg, ip) once a day for five days. At PN125, locomotor and anxiety-like effects were assessed with the open field test. At PN126, immobile behavior was assessed with the forced swimming test. At PN127, the frontal cerebral cortex was collected to evaluate dopamine and DOPAC levels. To verify whether varenicline was protective during the MPTP insult, a separate group of MPTP animals received varenicline from PN90 to PN124. MPTP reduced cortical dopamine content and increased dopamine turnover. Those effects were not reversed by varenicline treatment. Interestingly, varenicline reversed the MPTP-induced hyperactivity in the open field. Both maintenance of varenicline treatment during MPTP exposure or its interruption before MPTP exposure elicited similar results. No alterations were observed in anxiety-like behavior or in immobility time. Altogether, these findings suggested that varenicline treatment reduced the MPTP-induced hyperactivity, but did not protect against dopaminergic damage. Based on this partial protective effect, varenicline could exert neuroprotective effects on circuits that control motor activity in PD.

Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin

ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.

Investigation of Functional Connectivity During Working Memory Task and Hemispheric Lateralization in Left- and Right- Handers Measured by fNIRS

Working memory is regarded as a cognitive system with limited capacity, which is responsible for saving, manipulating, and remembering online information. The cognitive functions of the brain, such as language, understanding, planning, reasoning, and problem-solving, need working memory. Based on the previous studies, working memory is considered as a central function of frontal brain lobe. Among several protocols on assessing working memory function, the n-back task is regarded as one of the most common ones in the functional imaging studies of working memory. Functional near-infrared spectroscopy (fNIRS) is an optical imaging method for evaluating brain function, which measures nervous activities and hemodynamic response in the cerebral cortex. The present study aimed to assess functional connectivity in frontal brain lobe during conducting dual n-back task at three levels of memory loading (n = 0, 1, 2) by using fNIRS signals. The statistical population included 29 healthy volunteers, among which 11 and 18 ones were left- and right-handed, respectively. They performed a dual n-back task, and the change in the concentrations of Hb and HbO2 was measured by using 24 fNIRS channels existing in the frontal lobe. The matrix of functional connectivity was extracted and evaluated by using partial correlation criterion for all participants and each of right- and left-handed groups at every level of memory loading separately. The statistical analyses of Hb and HbO2 signals (p < 0.05) in each group represented the presence of a bilateral connection between two hemispheres and local connection ones between different areas in each hemisphere with more connectivity in the right hemisphere of the frontal cerebral cortex during conducting the dual n-back task. Based on the comparison of the results related to left- and right-handed groups, a difference was observed between their functional connectivity in some areas, as well as the number of connectivity between various areas. Right-handed participants more utilized the lateralization of the right hemisphere to perform task compared to left-handed did, while left-handed ones represented the decrease in lateralizing or distributing bilaterally in hemispheres, by indicating the difference between some of the brain connectivity were different in these participants by considering the dominance of one of the hemispheres in each of these two groups. In general, the results of the present study demonstrated that fNIRS data is considered as appropriate for assessing the functional connectivity between the different areas of the frontal cerebral cortex during conducting the working memory-related tasks.

Mechanisms of electroacupuncture for improving Alzheimer's disease from reducing β amyloid protein level

Alzheimer's disease (AD), a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary degeneration, is the most common type of dementia and has no incurable therapies at the moment. Electroacupuncture (EA) therapy has been widely used in clinical treatment of AD, and has attained approving effects. This article reviews the development of researches on the mechanisms of EA underlying improving AD by diminishing β amyloid protein （Aβ） neurotoxicity, from 1) up-regulating hippocampal cellular autophagy, 2) improving cerebral energy metabolism by activating oxidation stress-related factors peroxisome proliferator-activated receptor γ coactivator 1 alpha and sirtuin 1 in the hippocampus and frontal cerebral cortex, 3) relieving inflammatory reaction by lowering expression of tumor necrosis factor-alpha and high-mobility group box 1 and increasing expression of Interleukin 10, and 4) promoting degradation of Aβ1-42 by down-regulating expression of insulin degeneration enzyme, lipoprotein, transthyretin, apolipoprotein and α2 mcroglobulin. Meanwhile, a comprehensive clinical therapy of AD is proposed.

Ethanol exposure during the brain growth spurt affects social behavior and increases susceptibility to acute ethanol effects during adolescence in male mice.

The brain is particularly vulnerable to ethanol effects during its growth spurt. Outcomes of early ethanol exposure such as hyperactivity have been extensively investigated; however, persons with fetal alcohol spectrum disorder frequently have social impairments and are heavy drinkers. Despite that, scant information is available regarding the neurobiological basis of these latter behavioral issues. Here, Swiss mice exposed to ethanol (Etoh, 5g/kg i.p., alternate days) or saline during the brain growth spurt [postnatal day (PN) 2 to 8] were used to assess social behavior after an ethanol challenging during adolescence. At PN39, animals were administered with a single ethanol dose (1g/Kg) or water by gavage and were then evaluated in the three-chamber sociability test. We also evaluated corticosterone serum levels and the frontal cerebral cortex serotoninergic system. Etoh males showed reductions in sociability. Ethanol challenging reverted these alterations in social behavior, reduced corticosterone levels, and increased the 5-HT2 receptor binding of male Etoh mice. No alterations were observed in 5-HT and 5-HIAA contents. These data support the idea that ethanol exposure during the brain growth spurt impacts social abilities during adolescence, alters ethanol reexposure effects, and suggests that stress response and serotoninergic system play roles in this phenomenon.

Amyloid-beta peptide and phosphorylated tau in the frontopolar cerebral cortex and in the cerebellum of toothed whales: aging versus hypoxia.

ABSTRACTHypoxia could be a possible risk factor for neurodegenerative alterations in cetaceans’ brain. Among toothed whales, the beaked whales are particularly cryptic and routinely dive deeper than 1000 m for about 1 h in order to hunt squids and fishes. Samples of frontal cerebral and cerebellar cortex were collected from nine animals, representing six different species of the suborder Odontoceti. Immunohistochemical analysis employed anti-β-amyloid (Aβ) and anti-neurofibrillary tangle (NFT) antibodies. Six of nine (67%) animals showed positive immunolabeling for Aβ and/or NFT. The most striking findings were intranuclear Aβ immunopositivity in cerebral cortical neurons and NFT immunopositivity in cerebellar Purkinje neurons with granulovacuolar degeneration. Aβ plaques were also observed in one elderly animal. Herein, we present immunohistopathological findings classic of Alzheimer's and other neurodegenerative diseases in humans. Our findings could be linked to hypoxic phenomena, as they were more extensive in beaked whales. Despite their adaptations, cetaceans could be vulnerable to sustained and repetitive brain hypoxia.

Creation of Stereo Color Anatomical Charts Showing Nerve Fibers in the Cerebral Lobe and Gyrus of the Brain for Use in the MR Examination

In anatomical charts in conventional books, the pathways of nerve fibers are drawn in illustrations. Conversely, with diffusion tensor tractography (DTT), we can visually understand the trajectory of nerve fibers through color. We created a stereo color anatomical chart of the nerve fibers that can be used for magnetic resonance (MR) examination to diagnose the pathway of nerve fibers and that can be used to explain the results of MR examination to visually understand how nerve fiber information is transmitted from the frontal lobe, parietal lobe, occipital lobe, temporal lobe, cerebellar lobe, and cerebral cortex.