Frontal Cortex Research Articles

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review.

Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.

Elucidation of molecular mechanisms by which amyloid β1–42 fibrils exert cell toxicity

Abrupt aggregation of amyloid β1–42 (Aβ1–42) peptide in the frontal lobe is the expected underlying cause of Alzheimer's disease (AD). β-Sheet-rich oligomers and fibrils formed by Aβ1–42 exert high cell toxicity. A growing body of evidence indicates that lipids can uniquely alter the secondary structure and toxicity of Aβ1–42 aggregates. At the same time, underlying molecular mechanisms that determine this difference in toxicity of amyloid aggregates remain unclear. Using a set of molecular and biophysical assays to determine the molecular mechanism by which Aβ1–42 aggregates formed in the presence of cholesterol, cardiolipin, and phosphatidylcholine exert cell toxicity. Our findings demonstrate that rat neuronal cells exposed to Aβ1–42 fibrils formed in the presence of lipids with different chemical structure exert drastically different magnitude and dynamic of unfolded protein response (UPR) in the endoplasmic reticulum (ER) and mitochondria (MT). We found that the opposite dynamics of UPR in MT and ER in the cells exposed to Aβ1–42: cardiolipin fibrils and Aβ1–42 aggregates formed in a lipid-free environment. We also found that Aβ1–42: phosphatidylcholine fibrils upregulated ER UPR simultaneously downregulating the UPR response of MT, whereas Aβ1–42: cholesterol fibrils suppressed the UPR response of ER and upregulated UPR response of MT. We also observed progressively increasing ROS production that damages mitochondrial membranes and other cell organelles, ultimately leading to cell death.

Change in resting state functional connectivity following working memory training in individuals with repetitive negative thinking

BackgroundRepetitive negative thinking (RNT) symptoms, which are characterized by pervasive, uncontrollable negative thoughts, are common in individuals with mood, anxiety, and traumatic stress disorders. Inability to regulate the contents of working memory is a hypothesized etiological factor in RNT, suggesting that training to improve working memory may be beneficial. This study examined the effects of working memory training on resting state functional connectivity (rsFC) in individuals with elevated RNT and whether such changes would be associated with clinical improvement. MethodsWe conducted a secondary analysis of pre-post resting state data collected as part of a randomized controlled trial [NCT04912089] of working memory training interventions (n=42) compared to a waitlist control group (n=23). We hypothesized that individuals completing training would show increased rsFC between the two key intrinsic connectivity networks - default mode network (posterior cingulate cortex; PCC) and frontoparietal network (dorsolateral prefrontal cortex; dlPFC). We explored whether magnitude of rsFC change was associated with change in RNT symptom severity. ResultsrsFC increased between the PCC and regions including frontal and parietal cortex in the training group relative to waitlist. Increased connectivity between the PCC and superior frontal cortex was associated with RNT symptom reduction. ConclusionsThese data provide evidence that working memory training can modulate neural circuitry at rest in individuals with RNT. Results align with accounts of working memory training effects on large-scale neurocircuitry changes and suggest that these changes may contribute to clinical promise of this type of intervention on transdiagnostic RNT symptoms.

A fNIRS investigation of menopausal-related symptoms and brain cortical activity in menopause.

This study aimed to delineate the association between menopausal-related symptoms and brain cortical hemodynamics in peri-postmenopause women. Cross-sectional data from a total of 358 Han-Chinese women who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from August 2019 to August 2022. Menopausal-related symptoms were analyzed through Kupperman index (KMI) scale and PSQI scale, while cerebral blood flow was measured using a functional near-infrared spectroscopy (fNIRS). Multiple linear regression model was used to assess the risk factors for subregions of brain hemodynamic response. After adjusting for confounding factors, we identified that menopausal symptom (B=-1.575, 95% CI (-2.661, -0.488), p=0.005) and duration of menopause (B=-14.583, 95% CI (-26.753, -4.192), p=0.007) were independently associated with the lower brain hemodynamic response in the prefrontal lobe, while in the temporal lobe, overweight (BMI≥24kg/m2) was negatively associated with the lower brain cortical activity (B=-36.882, 95% CI (-72.708, -1.056), p=0.044) after adjusting for other confounding variables. Our findings proposed that menopausal symptom and overweight should be attached great importance to the postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as menopausal hormone therapy (MHT) of brain health in postmenopausal women.

Examining longitudinal associations between prenatal exposure to infections and child brain morphology

BackgroundMaternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Preclinical studies utilizing repeated measures of neuroimaging data furthermore suggest that effects of prenatal maternal infection on the offspring’s brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. This study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. MethodsWe leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean age 6, 10 and 14) to obtain cortical and subcortical measures of the offspring’s brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of maternal infection with child brain development over time. ResultsWe found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. ConclusionsOur results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.

Structural neuroimaging changes associated with subjective cognitive decline from a clinical sample

BackgroundAlzheimer’s disease (AD) is characterized by progressive deterioration of cognitive functions. Some individuals with subjective cognitive decline (SCD) are in the early phase of the disease and subsequently progress through the AD continuum. Although neuroimaging biomarkers could be used for the accurate and early diagnosis of preclinical AD, the findings in SCD samples have been heterogeneous. This study established the morphological differences in brain magnetic resonance imaging (MRI) findings between individuals with SCD and those without cognitive impairment based on a clinical sample of patients defined according to SCD-Initiative recommendations. Moreover, we investigated baseline structural changes in the brains of participants who remained stable or progressed to mild cognitive impairment or dementia. MethodsThis study included 309 participants with SCD and 43 healthy controls (HCs) with high-quality brain MRI at baseline. Among the 99 subjects in the SCD group who were followed clinically, 32 progressed (SCDp) and 67 remained stable (SCDnp). A voxel-wise statistical comparison of gray and white matter (WM) volume was performed between the HC and SCD groups and between the HC, SCDp, and SCDnp groups. XTRACT ATLAS was used to define the anatomical location of WM tract damage. Region-of-interest (ROI) analyses were performed to determine brain volumetric differences. White matter lesion (WML) burden was established in each group. ResultsVoxel-based morphometry (VBM) analysis revealed that the SCD group exhibited gray matter atrophy in the middle frontal gyri, superior orbital gyri, superior frontal gyri, right rectal gyrus, whole occipital lobule, and both thalami and precunei. Meanwhile, ROI analysis revealed decreased volume in the left rectal gyrus, bilateral medial orbital gyri, middle frontal gyri, superior frontal gyri, calcarine fissure, and left thalamus. The SCDp group exhibited greater hippocampal atrophy (p < 0.001) than the SCDnp and HC groups on ROI analyses. On VBM analysis, however, the SCDp group exhibited increased hippocampal atrophy only when compared to the SCDnp group (p < 0.001). The SCD group demonstrated lower WM volume in the uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and callosum forceps than the HC group. However, no significant differences in WML number (p = 0.345) or volume (p = 0.156) were observed between the SCD and HC groups. ConclusionsThe SCD group showed brain atrophy mainly in the frontal and occipital lobes. However, only the SCDp group demonstrated atrophy in the medial temporal lobe at baseline. Structural damage in the brain regions was anatomically connected, which may contribute to early memory decline.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Estimation of pathological lesion stage from brain images

BackgroundAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a disease responsible for cognitive impairment in adult humans. It is caused by mutations in the colony stimulating factor 1 receptor gene (CSF1R) or alanyl-transfer (t) RNA synthetase 2 (AARS2) gene and affects brain white matter. Settlement of stages of the pathological brain lesions (Oyanagi et al. 2017) from the findings of brain imaging will be inevitably essential for prognostication. MethodsMRI images of eight patients with ALSP were analyzed semiquantitatively. White matter degeneration was assessed on a scale of 0 to 4 (none, patchy, large patchy, confluent, and diffuse) at six anatomical points, and brain atrophy on a scale 0 to 4 (none, slight, mild, moderate, and severe) in four anatomical areas. The scores of the two assessments were then summed to give total MRI scores of 0–40 points. Based on the scores, the MRI features were classified as Grades (0–4). Regression analysis was applied to mutual association between mRS, white matter degeneration score, brain atrophy score, the total MRI score and disease duration. ResultsWhite matter degeneration score, brain atrophy score, and the total MRI score were significantly correlated with the disease duration. MRI Grades (2–4) based on the total MRI scores and the features of the images were well correlated with the pathological lesion stages (II - IV); i.e., ‘large patchy’ white matter degeneration in the frontal and parietal lobes (MRI Grade 2) corresponded to pathological Stage II, ‘confluent’ degeneration (Grade 3) to Stage III, and ‘diffuse’ degeneration (Grade 4) to Stage IV. ConclusionMRI Grades (2–4) resulted from the total MRI scores were well correlated with the pathological lesion Stages (II - IV).

MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study

Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration. In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and β coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype. We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61%] male and 133 [39%] female; 338 [100%] White) and 1312 neurologically healthy controls (611 [47%] male and 701 [53%] female; 1312 [100%] White). The MAPT H2 haplotype was associated with increased risk of Pick's disease compared with the H1 haplotype (OR 1·35 [95% CI 1·12 to 1·64], p=0·0021). MAPT H2 was not associated with age at onset (β -0·54 [95% CI -1·94 to 0·87], p=0·45) or disease duration (β 0·05 [-0·06 to 0·16], p=0·35). Although not significant after correcting for multiple testing, associations were observed at p less than 0·05: with risk of Pick's disease for the H1f subhaplotype (OR 0·11 [0·01 to 0·99], p=0·049); with age at onset for H1b (β 2·66 [0·63 to 4·70], p=0·011), H1i (β -3·66 [-6·83 to -0·48], p=0·025), and H1u (β -5·25 [-10·42 to -0·07], p=0·048); and with disease duration for H1x (β -0·57 [-1·07 to -0·07], p=0·026). The Pick's disease International Consortium provides an opportunity to do large studies to enhance our understanding of the pathobiology of Pick's disease. This study shows that, in contrast to the decreased risk of four-repeat tauopathies, the MAPT H2 haplotype is associated with an increased risk of Pick's disease in people of European ancestry. This finding could inform development of isoform-related therapeutics for tauopathies. Wellcome Trust, Rotha Abraham Trust, Brain Research UK, the Dolby Fund, Dementia Research Institute (Medical Research Council), US National Institutes of Health, and the Mayo Clinic Foundation.

Effect of Inactivation of Prefrontal Cortex on Sleep-Wake States in Rat

There is a large body of literature to support subcortical regulation of sleep-wake states, but there have been limited studies to investigate the role of cortex in sleep-wake regulation. Previously, we have demonstrated that cholinergic stimulation of prefrontal cortex can reverse general anesthesia and promote wakefulness in unanesthetized rats, and there is emerging evidence to suggest that the prefrontal cortex might be a critical node in arousal state control. To better understand the direct role of prefrontal cortex in the regulation of sleep-wake states, we quantified the effect of prefrontal cortex inactivation, via local tetrodotoxin (156 μM) infusion, on sleep architecture. Under surgical isoflurane anesthesia, adult Sprague Dawley rats (n=7 male) were instrumented with electrodes to record electroencephalogram (EEG) from frontal and parietal cortices, and electromyogram (EMG) from dorsal nuchal muscles. In addition, a bilateral guide cannula was implanted aimed at the medial prefrontal cortex for tetrodotoxin infusion. After at least a week of post-surgical recovery and conditioning to the recording chambers, rats received bilateral microinjection (500 nL) of either 156 μM tetrodotoxin or 0.9% saline (vehicle control). The tetrodotoxin and 0.9% saline infusions were performed 30-minutes before the start of lights-OFF period (8:00 pm) after which EEG and EMG data were recorded for 24h across dark and light cycles. The EEG and EMG data were manually scored (SleepSign, Kissei Comtec Inc.) in 4-second intervals into wakefulness, slow-wave sleep, and rapid eye movement sleep, and then averaged in 3h bins across 24h recording period. A linear mixed model was used to compare the changes in percent time spent in each state, mean duration per episode for each state, and mean number of episodes for each state, between the vehicle control and tetrodotoxin-infusion sessions. Inactivation of prefrontal cortex via tetrodotoxin infusion produced long-lasting statistically significant increase in slow-wave sleep (p&lt;0.05 for 0-3h, 4-6h, 7-9h, 10-12h, 13-15, 16-18, 22-24) and decrease in wakefulness (p&lt;0.05 for 0-3h, 4-6h, 10-12h) and rapid eye movement sleep (p&lt;0.05 for 7-9h, 10-12h, 13-15h). These data further support a causal contribution of prefrontal cortex in regulating arousal states. This work was supported by the National Institutes of Health (Bethesda, MD, USA) grant (R01 GM111293) to GAM and DP, and funding from the Department of Anesthesiology, University of Michigan Medical School, Ann Arbor. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Orbital reconstruction and volume in the correction of proptosis after resection of spheno-orbital meningiomas.

The objective of this study was to evaluate the effect of reconstruction and orbital volume on the reduction of proptosis in patients undergoing resection for spheno-orbital meningiomas. Additionally, potential predictors of optimal proptosis reduction after surgery were evaluated. Patients with spheno-orbital meningiomas who underwent resection at the authors' institution between 2005 and 2020 were evaluated retrospectively. The exophthalmos index (EI) was measured on pre- and postoperative imaging to quantify proptosis and calculate the primary outcome measure of proptosis reduction. Patients were excluded if they had no preoperative proptosis (i.e., EI < 1.1), prior resection, or insufficient imaging available for analysis. Clinical and surgical characteristics were collected, including sex, extent of resection, WHO grade, and rigid orbital reconstruction, and assessed as predictors of greater proptosis reduction. Additionally, orbital volumes of the affected and contralateral orbits were measured to correlate postoperative orbital volumes with proptosis reduction. Thirty-three patients, with a mean age of 53 years, met inclusion criteria. The majority of the patients were female (23, 69.7%), and most tumors were classified as WHO grade 1 (29, 87.9%). Six patients (18.2%) underwent rigid orbital reconstruction. The mean EI across all patients decreased from 1.36 ± 0.18 to 1.19 ± 0.15 (p < 0.001). Patients who underwent reconstruction had on average a 76.4% greater reduction in the EI (p = 0.036) and a 9.1 times higher odds of achieving a normal EI (< 1.1) compared with those who did not receive reconstruction (OR 9.1, p = 0.025). Additionally, patients without residual hyperostotic bone compressing the orbit had a 2.16 times greater reduction in EI (p = 0.039). A linear relationship between orbital volume ratios (affected/unaffected orbit) and proptosis reduction was observed (p = 0.029, r = 0.529), including at ratios > 1.0. This suggests that greater orbital volumes postoperatively correlated with greater reductions in proptosis. Three factors were identified that optimize proptosis correction. First, all abnormal bone compressing the orbital contents must be removed completely. Second, rigid orbital reconstruction leads to improved proptosis correction, possibly by preventing frontal lobe and dural reconstruction from descending onto the compressed orbit. Third, aiming for an orbital volume slightly larger than the contralateral normal side leads to improved proptosis correction.

An EEG study to understand semantic and episodic memory retrieval in creative processes

AbstractThis study aimed to identify and compare the EEG activities associated with semantic and episodic memory retrieval during creative processes. Episodic and semantic memory induction studies were conducted and EEG was used to collect data. The results showed that (i) Episodic and semantic memory retrieval are related to the frontal lobe area; (ii) Semantic memory retrieval is evoked more swiftly compared with episodic memory retrieval (ii) Prior to episodic memory retrieval, semantic memory retrieval is evoked first.

Mapping the neural mechanism that distinguishes between holistic thinking and analytic thinking

Holistic and analytic thinking are two distinct modes of thinking used to interpret the world with relative preferences varying across cultures. While most research on these thinking styles has focused on behavioral and cognitive aspects, a few studies have utilized functional magnetic resonance imaging (fMRI) to explore the correlations between brain metrics and self-reported scale scores. Other fMRI studies used single holistic and analytic thinking tasks. As a single task may involve processing in spurious low-level regions, we used two different holistic and analytic thinking tasks, namely the frame-line task and the triad task, to seek convergent brain regions to distinguish holistic and analytic thinking using multivariate pattern analysis (MVPA). Results showed that brain regions fundamental to distinguish holistic and analytic thinking include the bilateral frontal lobes, bilateral parietal lobes, bilateral precentral and postcentral gyrus, bilateral supplementary motor areas, bilateral fusiform, bilateral insula, bilateral angular gyrus, left cuneus, and precuneus, left olfactory cortex, cingulate gyrus, right caudate and putamen. Our study maps brain regions that distinguish between holistic and analytic thinking and provides a new approach to explore the neural representation of cultural constructs. We provide initial evidence connecting culture-related brain regions with language function to explain the origins of cultural differences in cognitive styles.

Changes in postural stability after cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus.

In patients with idiopathic normal pressure hydrocephalus (iNPH), the characteristics of balance disturbance are not as well understood as those related to gait. This study examined changes in postural stability in quiet standing after the cerebrospinal fluid tap test (CSFTT) in these patients. Furthermore, the study explored the relationship between the amount of spontaneous body sway and both gait and executive function. All patients diagnosed with iNPH underwent CSFTT. We evaluated their center of pressure (COP) measurements on a force plate during quiet standing, both pre- and post-CSFTT. Following the COP measurements, we calculated COP parameters using time and frequency domain analysis and assessed changes in these parameters after CSFTT. At pre-CSFTT, we assessed the Timed Up and Go (TUG) and the Frontal Assessment Battery (FAB). We investigated the relationship between COP parameters and the TUG and FAB scores at pre-CSFTT. A total of 72 patients with iNPH were initially enrolled, and 56 patients who responded positively to CSFTT were finally included. Post-CSFTT, significant improvements were observed in COP parameters through time domain analysis. These included the velocity of COP (vCOP), root-mean-square of COP (rmsCOP), turn index, torque, and base of support (BOS), compared to the pre-CSFTT values (p < 0.05). In the frequency domain analysis of COP parameters post-CSFTT, there was a decrease in both the peak and average of power spectral density (PSD) values in both the anteroposterior (AP) and mediolateral (ML) directions below 0.5 Hz (p < 0.05). In addition, the TUG scores showed a positive correlation with vCOP, rmsCOP, turn index, torque, BOS, and both the peak and average PSD values in the AP and ML directions below 0.5 Hz (p < 0.05). The FAB scores demonstrated a negative correlation with vCOP, rmsCOP, turns index, BOS, and both peak and average PSD values in the AP direction below 0.5 Hz (p < 0.05). In patients with iNPH who responded to CSFTT, there was an improvement in spontaneous body sway during quiet standing after CSFTT. Increased spontaneous sway is associated with impaired gait and frontal lobe function. This may be linked to impaired cortico-cortical and cortico-subcortical circuits in patients with iNPH.

Atypical meningiomas compared to other WHO Grade 2 meningiomas: Histological features and prognosis.

To study each atypical feature in atypical meningioma versus other grade 2 meningiomas and its possible relation to recurrence. This is a retrospective study of patients with WHO grade 2 meningioma operated in our institution between 01/2008 and 12/2020. The rate of recurrence, reoperation and readmission were recorded during the follow-up period. A statistical analysis was done to determine the significance of each pathological feature in regard to recurrence. A total of 74 patients were included as WHO grade 2 meningioma with 60 (81%) patients having an AM and 14 (19%) patients with chordoid or clear cell meningioma. The mean age was 51 years±14. The most common location was meningioma abutting the frontal lobe (convexity). Major atypical features were more noted in the AM, however, there was no significant difference between AM and other types of meningioma. Increased Nuclear cytoplasmic ratio and cellularity were found significantly more in AM. The recurrence rate was 16.2%. No specific pathology feature (major or minor) nor the type of Grade 2 meningioma was significantly related to recurrence. The types of WHO grade 2 meningiomas have similar prognosis and recurrence rates. There is no significant difference between the atypical features in indicating a more aggressive nature or risk of recurrence in grade 2 meningiomas.

229. Interactive Effects of Depression and Cumulative Head Impacts on Frontal Lobe Thickness in Elite Former Athletes

229. Interactive Effects of Depression and Cumulative Head Impacts on Frontal Lobe Thickness in Elite Former Athletes

Alteration of the bile acid pool attenuates neuroinflammation in the EAE mouse model of Multiple Sclerosis

Bile acids are critical signaling molecules that mediate gut crosstalk with other organs, including the brain. The primary bile acids, such as chenodeoxycholic acid (CDCA), are synthesized in the liver and modified by gut bacteria to generate secondary bile acids like the 12α-hydroxylated deoxycholic acid (DCA). Bile acids are effciently absorbed in the distal ileum, and recent studies have implicated them in neuroinflammation and the pathophysiology of several neurological diseases such as Multiple Sclerosis (MS). However, the specific effects of different types of bile acids on MS have not been thoroughly investigated. We hypothesize that bile acids differentially affect neuroinflammation and that treatment with cholestyramine (bile acid sequestrant) modulates astrocyte activation in a mouse model of MS. Methods: Primary astrocyte cultures were prepared from 6-10-week-old C57BL/6 mice and incubated with cytokines in the presence and absence of bile acids. The expression of inflammatory and astrocyte activation markers was assessed by real-time qPCR. The effects of blocking bile acid absorption on MS were examined using the established Experimental Autoimmune Encephalomyelitis (EAE) mouse model of MS in 8-week-old female mice (C57BL/6). Mice were fed either a standard chow diet or a standard chow diet supplemented with 2% cholestyramine, a bile acid sequestrant, to block bile acid absorption. Statistical significance between groups was determined by an unpaired T-test. Results: Astrocytes treated with cytokines (TNF-α, 10 ng/mL, IL1-β, 10 ng/mL, 24 h) significantly increased the mRNA expression of TNF-α and IL1-β and markers of astrocyte activation, lipocalin 2 (LCN2), and Serpina3n. Co-treatment with cytokines and CDCA but not DCA (50 μM, 24 h) significantly decreased TNF-α (~56%, p&lt;0.01), IL1-β (~40%, p&lt;0.01), LCN2 (~26%, p&lt;.001), and Serpina3n (~44%, p&lt;.001), vs cytokines alone. The taurine-conjugate, TCDCA, also resulted in significant decreases in the expression of TNF-α (~72%, p&lt;0.001), IL1-β (~53%, p&lt;.001), LCN2 (~30%, p&lt;0.05), and Serpina3n (~16%, p&lt;0.01), suggesting an anti-inflammatory effect specific to CDCA and its taurine conjugate on astrocytes. Cholestyramine treatment in EAE mice was associated with significant reductions in the mRNA expression of TNF-α (~40%, p&lt;0.05) and Serpina3n (~30%, p= 0.217) in the frontal cortex of the brain. Together, these data imply that altering the composition of the bile acid pool may be a viable therapeutic strategy for MS patients by attenuating neuroinflammation. University of Illinois at Chicago, JBVMC, Chicago, IL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Occipital Connectivity Networks Mediate the Neural Effects of Childhood Maltreatment on Depressive Symptoms in Major Depressive Disorder

BackgroundChildhood maltreatment (CM) is a well-established risk factor for major depressive disorder (MDD). The neural mechanisms linking childhood maltreatment experiences to changes in brain functional networks and the onset of depression are not fully understood. MethodsIn this study, we enrolled 66 patients with MDD and 31 healthy controls who underwent resting-state fMRI scans and neuropsychological assessments. We employed multivariate linear regression to examine the neural associations of CM and depression, specifically focusing on the bilateral occipital functional connectivity (OFC) networks relevant to MDD. Subsequently, a two-step mediation analysis was conducted to assess whether the OFC network mediated the relationship between CM experiences and the severity of depression. ResultsOur study showed that patients with MDD exhibited reduced OFC strength, particularly in the occipito-temporal, parietal, and premotor regions. These reductions were negatively correlated with CM scores and the severity of depression. Notably, the overlapping regions in the bilateral OFC networks, affected by both CM experiences and depressive severity, were primarily observed in the bilateral cuneus, left angular and calcarine, as well as the right middle frontal cortex and superior parietal cortex. Furthermore, the altered strengths of the OFC networks were identified as positive mediators of the impact of CM history on depression symptoms in patients with MDD. ConclusionWe have demonstrated that early exposure to CM may increase vulnerability to depression by influencing the brain's network. These findings provide new insights into understanding the pathological mechanism underlying depressive symptoms induced by CM.

Symptomatic arachnoid cyst of the left frontal convexity in an adult: A case report.

Background: Arachnoid cysts are benign intra-arachnoidal cystic lesions whose content is cerebrospinal fluid. Most locations is supratentorial in the middle cranial fossa. The location in the convexity of the frontal lobe is unusual. Case Description: A previously healthy 21-year-old man was admitted to the emergency department for post-seizure loss of consciousness. Following imaging studies, a large cystic lesion in the convexity of the left frontal lobe was found. Total excision of the cyst wall was performed after craniotomy. The histology confirms the diagnosis of arachnoid cyst. Patient was followed up for the last 4 months without any symptoms or neurological deficit. Conclusion: Arachnoid Cysts in the frontal convexity are rare. Clinical symptoms is nonspecific and depend on the volume. The definite treatment if it's symptomatic is surgery.

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.