Frontal Cortex Research Articles

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent adifferential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. We retrospectively analyzed the preoperative imaging of 45patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). Thirty-nine patients were classified as having an ependymoma, 35with aZFTA fusion and four with aYAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), acystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Influence of an improvement in frontal lobe hemodynamics on neurocognitive function in adult patients with moyamoya disease.

In adults, moyamoya disease (MMD) often presents with slight neurocognitive impairment, which may result from frontal lobe hemodynamic insufficiency. In this study, we performed revascularization surgery by superficial temporal artery-anterior cerebral artery (ACA) direct bypass in 20 adults with MMD with poor anterograde ACA flow (Group M). The pre- and postoperative neurocognitive test results of these patients were retrospectively analyzed. The comparative group (Group C) included 23 patients with unruptured aneurysms or brain tumors who underwent craniotomy, as well as the same neurocognitive tests as Group M. We calculated the compositive frontal lobe function index (CFFI) based on the results of seven neurocognitive tests for each patient, and the difference between the pre- and postoperative CFFI values (CFFI Post - Pre) was compared between the two groups. Frontal perfusion improved postoperatively in all patients in Group M. The CFFI Post - Pre was significantly higher in Group M than in Group C (0.23 ± 0.44 vs. - 0.20 ± 0.32; p < 0.001). After adjusting for postoperative age, sex, preoperative non-verbal intelligence quotient, and preoperative period of stress, Group M had a significantly higher CFFI Post - Pre than Group C in the multiple regression analysis (t value = 4.01; p < 0.001). Improving frontal lobe hemodynamics might be the key for improving neurocognitive dysfunction in adults with MMD. The surgical indication and method should be considered from the perspective of both stroke prevention and neurocognitive improvement or protection.

Impacts of exposure to and subsequent discontinuation of clozapine on tripartite synaptic transmission.

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but its discontinuation leads to discontinuation syndrome/catatonia complicated by benzodiazepine-resistance and rhabdomyolysis. This study determined time-dependent effects of exposure and subsequent discontinuation of clozapine on expression of connexin43, 5-HT receptors, intracellular L-β-aminoisobutyrate (L-BAIBA) and 2nd-messengers and signalling of AMPK, PP2A and Akt in cultured astrocytes and rat frontal cortex. Intracellular L-BAIBA levels increased during clozapine exposure but immediately recovered after discontinuation. Both exposure to clozapine and L-BAIBA increased connexin43 and signalling of AMPK/Akt time-dependently, but reduced PP2A signalling, 5-HT receptor expression and IP3 level. These changes recovered within 2 weeks after discontinuation, while 5-HT receptors and IP3 transiently increased during the recovery process. L-BAIBA activated AMPK signalling, leading to attenuated PP2A signalling. Astroglial D-serine release was increased by clozapine exposure but continued to increase within 1 week after discontinuation via activation of IP3 receptor function. Clozapine discontinuation restored PP2A signalling due to decreased L-BAIBA, increased 5-HT receptor expression via probably enhanced 5-HT receptor recycling, but increased astroglial D-serine release persisted by transiently activated IP3 receptors via transiently increased IP3 level. Decreased L-BAIBA caused by clozapine discontinuation is, at least partially, involved in the transiently increased 5-HT receptor and astroglial D-serine release.

Patterns of glucose hypometabolism can help differentiate FTLD-FET from other types of FTLD.

FTLD-FET is a newly described subtype of frontotemporal lobar degeneration (FTLD characterized by pathologic inclusions of FET proteins: fused in sarcoma (FUS), Ewing sarcoma, and TATA-binding protein-associated factor 2N (TAF15)). Severe caudate volume loss on MRI has been linked to FTLD-FUS, yet glucose hypometabolism in FTLD-FET has not been studied. We assessed [18F] fluorodeoxyglucose PET (FDG-PET) hypometabolism in FTLD-FET subtypes and compared metabolism to FTLD-tau and FTLD-TDP. We retrospectively reviewed medical records of 26 autopsied FTLD patients (six FTLD-FET, ten FTLD-Tau, and ten FTLD-TDP) who had completed antemortem FDG-PET. We evaluated five regions, caudate nucleus, medial frontal cortex, lateral frontal cortex, and medial temporal using a 0-3 visual rating scale and validated our findings quantitatively using CORTEX-ID suite Z scores. Of the six FTLD-FET cases (three females) with median age at onset = 36, three were atypical FTLD-U (aFTLD-U) and three were neuronal intermediate filament inclusion disease (NIFID). bvFTD was the most common presentation. Four of the six FTLD cases (3 aFTLD-U + 1 NIFID) showed prominent caudate hypometabolism relatively early in the disease course. FTLD-tau and FTLD-TDP did not show early prominent caudate hypometabolism. Hypometabolism in medial and lateral temporal cortex was associated with FTLD-TDP, while FTLD-tau had normal-minimal regional metabolism. Prominent caudate hypometabolism, especially early in the disease course, appears to be a hallmark feature of the aFTLD-U subtype of FTLD-FET. Assessing caudate and temporal hypometabolism on FDG-PET will help to differentiate FTLD-FET from FTLD-tau and FTLD-TDP.

Characterization of white matter hyperintensities in Down syndrome.

In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

Texture-based morphometry in relation to apolipoprotein ε4 genotype, ageing and sex in a midlife population.

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross-sectional study, we investigated textural properties of T1-weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT-Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel-based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non-carriers. Textural maps were generated and were subsequently harmonised using voxel-wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non-carriers at midlife and have established associations of textural features with ageing and sex.

Menstrual cycle-driven hormone concentrations co-fluctuate with white and gray matter architecture changes across the whole brain.

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

A portable affective computing system for identifying mate preference

Recognizing an individual’s preference state for potential romantic partners based on electroencephalogram (EEG) signals holds significant practical value in enhancing matchmaking success rates and preventing romance fraud. Despite some progress has been made in this field, challenges such as high-dimensional feature space and channel redundancy limited the technology’s practical application. The aim of this study is to explore the most discriminative EEG features and channels, in order to enhance the recognition performance of the system, while maximizing the portable and practical value of EEG-based systems for recognizing romantic attraction. To achieve this goal, we first conducted an interesting simulated dating experiment to collect the necessary data. Next, EEG features were extracted from various dimensions, including band power and asymmetry index features. Then, we introduced a novel method for EEG feature and channel selection that combines the sequential forward selection (SFS) algorithm with the frequency-based feature subset integration (FFSI) algorithm. Finally, we used the random forest classifier (RFC) to determine a person's preference state for potential romantic partners. Experimental results indicate that the optimal feature subset, selected using the SFS-FFSI method, attained an average classification accuracy of 88.42%. Notably, these features were predominantly sourced from asymmetry index features of electrodes situated in the frontal, parietal, and occipital lobes.

Quantitative assessment of enlarged perivascular spaces via deep-learning in community-based older adults reveals independent associations with vascular neuropathologies, vascular risk factors, and cognition

Abstract Enlarged perivascular spaces (EPVS) are common in older adults, but their neuropathologic correlates are unclear mainly because most work to date has relied on visual rating scales and/or clinical cohorts. The present study first developed a deep learning model for automatic segmentation, localization and quantification of EPVS in ex-vivo brain MRI, and then used this model to investigate the neuropathologic, clinical, and cognitive correlates of EPVS in 817 community-based older adults that underwent autopsy. The new method exhibited high sensitivity in detecting EPVS as small as 3 mm3, good segmentation accuracy and consistency. Most EPVS were located in the frontal lobe, but the highest density was observed in the basal ganglia. EPVS in the cerebrum and specifically in the frontal lobe were associated with infarcts independent of other neuropathologies, while temporal and occipital EPVS were associated with cerebral amyloid angiopathy. EPVS in most brain lobes were also associated with diabetes mellitus independently of neuropathologies, while basal ganglia EPVS were independently associated with hypertension, supporting the notion of independent pathways from diabetes and hypertension to EPVS. Finally, EPVS were associated with lower cognitive performance independently of neuropathologies and clinical variables, suggesting that EPVS represent additional abnormalities contributing to lower cognition.

Study on the relationship between EEG and salivary IgE under step-change temperature environments

The salivary immunoglobulin E (IgE) level that usually acts as an indicator of human immunity could change significantly with the air temperature. Electroencephalography (EEG) is a commonly used technique to assess the thermal responses of the human body to the environment. However, the relations between them under step-change temperatures would still need more evidence. Experiments were conducted in this study to explore the EEG–IgE relation. Three step-changed temperature conditions in the controlled environment by a climate chamber were selected in this study, under which the air temperature was suddenly transitioned from a low temperature of 15°C to higher temperatures of 18°C, 24°C and 30°C, respectively, before returning to the initial low-temperature condition. The subjective questionnaires, the EEG signals and the salivary samples from 14 subjects in these three step-changed temperature conditions were collected. Results showed that the thermal comfort voting was significantly correlated with the EEG spectral power and the IgE concentration. In addition, a significant negative correlation between the frontal lobe spectral power and the salivary IgE changes was observed. The spectral power of the frontal lobe could be used as an objective indicator to evaluate the salivary IgE levels under step-change temperature environments. This study has provided some guidance for future studies of the human immunity responses to the indoor environment in different seasons.

Magnetic resonance imaging pattern recognition of metabolic and neurodegenerative encephalopathies in dogs and cats

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

Examining Neural Correlates of Sexual Preferences between Persian Homo- and Heterosexual Males Using Psychological Assessments and Functional Magnetic Resonance Imaging in Specifying Cognitive Map: A Limited and Cross-sectional Study

AbstractAlthough the brain is an important part of a person's sexual life, little is known about the correlations between sexual response and brain activation. This study examines brain responses through clinical testing to reveal several brain structures whose activation is relevant to sexual arousal besides psychological testing according to the common traditional values and standards of Iranian society. Based on an initial self-report, 25 homosexual and 25 heterosexual males participated in this test to elucidate the identity and sexual trends via the Minnesota Multiphasic Personality Inventory (MMPI-2). Also, an fMRI technique—by presenting distinct homo- and heterosexual sex erotic pictures during the test—was employed in neural correlates of sexual arousal via blood oxygen level dependent (BOLD) signal measuring and Statistical Parametric Mapping analysis. In five selected homosexuals by the most appropriate MMPI test score, brain activities were significantly detected in the midbrain, amygdala, anterior cingulate gyrus, frontal cortex, orbitofrontal cortex, globus pallidus, thalamus, and putamen when the participant saw the erotic pictures during the test, which were responsive to sexual arousal. Also, bilateral caudate nucleus, left angular gyrus, and bilateral pallidum were activated but five selected heterosexuals showed no activation in these areas (p &lt; 0.001). Likewise, the MMPI method confirmed that homosexuality was relevant to diverse life positions, and biological and socioeconomic aspects. The maximum positive correlations were pairwise found in the parietal lobule by r = 0.61 (p &lt; 0.05) and in the frontal gyrus by r = 0.64 (p = 0.10), and the minimum negative correlations were in globus pallidus by r = − 0.18 (p &lt; 0.10) and r = − 0.16 (p &lt; 0.10) for homosexuals and heterosexuals, correspondingly. These results may be useful for understanding the different neural mechanisms of personality recognition and sexual orientation changes while incorporating the individual's history and experience simultaneously into the assessment.

Chromosome 7 gain compensates for chromosome 10 loss in glioma.

The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers. This phenomenon has been investigated since the late 1980s without resolution. Expanding beyond previous gene-centric studies, we investigated the co-occurrence in a genome-wide manner taking an evolutionary perspective. Mining of large-scale tumor aneuploidy data confirmed the previous finding of a small-scale longitudinal study that the most likely order is chromosome 10 loss followed by chromosome 7 gain. Extensive analysis of genomic and transcriptomic data from both patients and cell lines revealed that this co-occurrence can be explained by functional rescue interactions that are highly enriched on chromosome 7, which could potentially compensate for any detrimental consequences arising from the loss of chromosome 10. Transcriptomic data from various normal, non-cancerous human brain tissues were analyzed to assess which tissues may be most predisposed to tolerate compensation of chromosome 10 loss by chromosome 7 gain. The analysis indicated that the pre-existing transcriptomic states in the cortex and frontal cortex, where gliomas arise, are more favorable than other brain regions for compensation by rescuer genes that are active on chromosome 7. Collectively, these findings suggest that the phenomenon of chromosome 10 loss and chromosome 7 gain in gliomas is orchestrated by a complex interaction of many genes residing within these two chromosomes and provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.

Combined Statistical Analysis of Glioblastoma Outcomes—A Neurosurgical Single-Institution Retrospective Study

Background and Objectives: Notwithstanding the major progress in the management of cancerous diseases in the last few decades, glioblastoma (GBM) remains the most aggressive brain malignancy, with a dismal prognosis, mainly due to treatment resistance and tumoral recurrence. In order to diagnose this disease and establish the optimal therapeutic approach to it, a standard tissue biopsy or a liquid biopsy can be performed, although the latter is currently less common. To date, both tissue and liquid biopsy have yielded numerous biomarkers that predict the evolution and response to treatment in GBM. However, despite all such efforts, GBM has the shortest recorded survival rates of all the primary brain malignancies. Materials and Methods: We retrospectively reviewed patients with a confirmed histopathological diagnosis of glioblastoma between June 2011 and June 2023. All the patients were treated in the Third Neurosurgical Department of the Clinical Emergency Hospital “Bagdasar-Arseni” in Bucharest, and their outcomes were analyzed and presented accordingly. Results: Out of 518 patients in our study, 222 (42.8%) were women and 296 (57.14%) were men. The most common clinical manifestations were headaches and limb paralysis, while the most frequent tumor locations were the frontal and temporal lobes. The survival rates were prolonged in patients younger than 60 years of age, in patients with gross total tumoral resection and less than 30% tumoral necrosis, as well as in those who underwent adjuvant radiotherapy. Conclusions: Despite significant advancements in relation to cancer diseases, GBM is still a field of great interest for research and in great need of new therapeutic approaches. Although the multimodal therapeutic approach can improve the prognosis, the survival rates are still short and the recurrences are constant.

Efficacy of intra-arterial carboplatin and bevacizumab in the C6 rat glioma model of glioblastoma multiforme

BackgroundUtilizing an endovascular rat glioma model, this study aimed to analyze the efficacy of intra-arterial (IA) carboplatin and bevacizumab delivery with blood-brain barrier breakdown (BBBB) for glioblastoma treatment.MethodsC6-glioma cells were...

Cortical Thickness Correlates of Go/No-go and Motor Sequencing in Mild Cognitive Impairment and Suspected Alzheimer Disease Dementia.

While the cognitive hallmark of typical Alzheimer's disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted. We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group. First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task. We then examined correlations between neurobehavioral task performance and the thickness of frontal cortical regions, AD signature regions, broader unbiased brain regions, and white matter hyperintensities (WMH). Participants with MCI performed worse than healthy controls, but better than participants with suspected AD dementia on both tasks. Both GNG and FEP (to a slightly greater extent) tasks showed diffuse associations with most AD signature regions and multiple additional regions within the temporal, parietal, and occipital cortices. Similarly, both tasks showed significant associations with all other cognitive tasks examined. Of the frontal regions examined, only the middle frontal gyrus and pars opercularis were associated with performance on these tasks. Interactions between the precuneus and transtemporal gyri were most predictive of GNG task performance, while the interaction between superior temporal and lingual gyri was most predictive of FEP task performance. This study replicates difficulties with both GNG and FEP tasks in participants with MCI and AD dementia. Both tasks showed widespread associations with the cortical thickness of various brain structures rather than localizing to frontal regions, consistent with the diffuse nature of AD.

Analyzing brain-activation responses to auditory stimuli improves the diagnosis of a disorder of consciousness by non-linear dynamic analysis of the EEG

Although auditory stimuli benefit patients with disorders of consciousness (DOC), the optimal stimulus remains unclear. We explored the most effective electroencephalography (EEG)-tracking method for eliciting brain responses to auditory stimuli and assessed its potential as a neural marker to improve DOC diagnosis. We collected 58 EEG recordings from patients with DOC to evaluate the classification model’s performance and optimal auditory stimulus. Using non-linear dynamic analysis (approximate entropy [ApEn]), we assessed EEG responses to various auditory stimuli (resting state, preferred music, subject’s own name [SON], and familiar music) in 40 patients. The diagnostic performance of the optimal stimulus-induced EEG classification for vegetative state (VS)/unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) was compared with the Coma Recovery Scale-Revision in 18 patients using the machine learning cascade forward backpropagation neural network model. Regardless of patient status, preferred music significantly activated the cerebral cortex. Patients in MCS showed increased activity in the prefrontal pole and central, occipital, and temporal cortices, whereas those in VS/UWS showed activity in the prefrontal and anterior temporal lobes. Patients in VS/UWS exhibited the lowest preferred music-induced ApEn differences in the central, middle, and posterior temporal lobes compared with those in MCS. The resting state ApEn value of the prefrontal pole (0.77) distinguished VS/UWS from MCS with 61.11% accuracy. The cascade forward backpropagation neural network tested for ApEn values in the resting state and preferred music-induced ApEn differences achieved an average of 83.33% accuracy in distinguishing VS/UWS from MCS (based on K-fold cross-validation). EEG non-linear analysis quantifies cortical responses in patients with DOC, with preferred music inducing more intense EEG responses than SON and familiar music. Machine learning algorithms combined with auditory stimuli showed strong potential for improving DOC diagnosis. Future studies should explore the optimal multimodal sensory stimuli tailored for individual patients.Trial registration: The study is registered in the Chinese Registry of Clinical Trials (Approval no: KYLL-2023-414, Registration code: ChiCTR2300079310).

Protection from oxygen-glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes.

Preterm birth results in an increased risk of neonatal brain injury and neurobehavioural disorders. Despite the seriousness of these adverse outcomes, there are currently no effective therapies to protect the vulnerable developing brain. We propose that neurosteroid replacement therapy may be a novel approach in reducing detrimental neurological outcomes following preterm birth. The use of guinea pig primary neuronal and oligodendrocyte cultures with relevance to late gestation allows insight into the mechanisms behind the effectiveness of these treatments. Primary neuronal and oligodendrocyte cultures were derived from fetal guinea pig frontal cortex brain tissue at gestational age 62 (GA62). Cell cultures were pre-treated with either etifoxine (5µM) or zuranolone (1µm) for 24h prior to insult. Cells were then exposed to either oxygen-glucose deprivation (OGD; 0% O2 and no glucose DMEM; preterm birth insult) or sham (standard cell culture conditions; 25mM DMEM) for 2h. Lactate dehydrogenase assay (LDH) was performed following OGD as a measure of cytotoxicity. Relative mRNA expression of key neuronal and oligodendrocyte markers, as well as neuronal receptors and transporters, were quantified using high throughput (Fluidigm) RT-PCR. OGD significantly increased cellular cytotoxicity in both neurons and oligodendrocytes. Additionally, key neuronal marker mRNA expression was reduced following OGD, and oligodendrocytes displayed arrested mRNA expression of key markers of lineage progression. Treatment with etifoxine restored a number of parameters back to control levels, whereas treatment with zuranolone provided a robust improvement in all parameters examined. This study has demonstrated the neuroprotective potential of neurosteroid replacement therapy in a model of hypoxia related to preterm birth. Neuroprotection appears to be mediated through glutamate reduction and increased brain derived neurotrophic factor (BDNF). Future work is warranted in examining these treatments in vivo, with the overall aim to suppress preterm associated brain damage and reduce long term outcomes for affected offspring.

Structure-function coupling reveals the brain hierarchical structure dysfunction in Alzheimer's disease: A multicenter study.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive decline. To date, the specific dysfunction in the brain's hierarchical structure in AD remains unclear. We introduced the structural decoupling index (SDI), based on a multi-site data set comprising functional and diffusion-weighted magnetic resonance imaging data from 793 subjects, to assess their brain hierarchy. Compared to normal controls (NCs), individuals with AD exhibited increased SDI within the posterior superior temporal sulcus, insular gyrus, precuneus, hippocampus, amygdala, postcentral gyrus, and cingulate gyrus; meanwhile, the patients with AD demonstrated decreased SDI in the frontal lobe. The SDI in those regions also showed a significant correlation with cognitive ability. Moreover, the SDI was a robust AD neuroimaging biomarker capable of accurately distinguishing diagnostic status (area under the curve [AUC]=0.86). Our findings revealed the dysfunction of the brain's hierarchical structure in AD. Furthermore, the SDI could serve as a promising neuroimaging biomarker for AD. This study utilized multi-center, multi-modal data from East Asian populations. We found an increased spatial gradient of the structure decoupling index (SDI) from sensory-motor to higher-order cognitive regions. Changes in SDI are associated with energy metabolism and mitochondria. SDI can identify Alzheimer's disease (AD) and further uncover the disease mechanisms of AD.

Osteopontin: A novel marker of pre-symptomatic sporadic Alzheimer's disease.

We investigate the role of osteopontin (OPN) in participants with Pre-symptomatic Alzheimer's disease (AD), mild cognitive impairment (MCI), and in AD brains. Cerebrospinal fluid (CSF) OPN, AD, and synaptic biomarker levels were measured in 109 cognitively unimpaired (CU), parental-history positive Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) participants, and in 167 CU and 399 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. OPN levels were examined as a function of amyloid beta (Aβ) and tau positivity. Survival analyses investigated the link between OPN and rate of conversion to AD. In PREVENT-AD, CSF OPN was positively correlated with synaptic biomarkers. In PREVENT-AD and ADNI, OPN was elevated in CSF Aβ42/40(+)/total tau(+) and CSF Aβ42/40(+)/phosphorylated tau181(+) individuals. In ADNI, OPN was increased in Aβ(+) positron emission tomography (PET) and tau(+) PET individuals, and associated with an accelerated rate of conversion to AD. OPN was elevated in autopsy-confirmed AD brains. Strong associations between CSF OPN and key markers of AD pathophysiology suggest a significant role for OPN in tau neurobiology, particularly in the early stages of the disease. In the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease cohort, we discovered that cerebrospinal fluid (CSF) osteopontin (OPN) levels can indicate early synaptic dysfunction, tau deposition, and neuronal loss in cognitively unimpaired elderly with a parental history. CSF OPN is elevated in amyloid beta(+) positron emission tomography (PET) and tau(+) PET individuals. Elevated CSF OPN is associated with an accelerated rate of conversion to Alzheimer's disease (AD). Elevated CSF OPN is associated with an accelerated rate of cognitive decline on the Alzheimer's Disease Assessment Scale-Cognitive subscale 13, Montreal Cognitive Assessment, Mini-Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes. OPN mRNA and protein levels are significantly upregulated in the frontal cortex of autopsy-confirmed AD brains.