Brain Regions Research Articles

Omeprazole affects the expression of serotonin-1A in the brain regions and alleviates anxiety in rat model of immobilization-induced stress.

Omeprazole, a drug of choice for the management of gastric hyperacidity, influences serotonergic neurotransmission in brain regions and its long-term use is known to cause stress-related behavioral deficits including anxiety. Aim of the current study was to explore the effects of omeprazole treatment on immobilization-induced anxiety in rats, specifically on the role of serotonin (5-HT). In view of the role of serotonin-1A (5-HT1A) autoreceptor in the availability of 5-HT in brain regions, mRNA expression of this autoreceptor was performed in raphe nuclei. Similarly, because of the role of hippocampal 5-HT neurotransmission in anxiety-like disorders, expression of the 5-HT1A heteroreceptors was determined in this region. We found that the treatment with omeprazole reduces anxiety-like behavior in rats, increases the expression of 5-HT1A autoreceptor in the raphe and decreases the hippocampal expression of 5-HT1A heteroreceptor. This suggests a role of 5-HT1A receptor types in omeprazole-induced behavioral changes. It also indicates a potential role of omeprazole in the management of serotonergic disorders.

Sex differences in gray matter, white matter, and regional brain perfusion in young, healthy adults.

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between gray and white matter or without assessing regional CBF. Thus fundamental sex differences in regional or whole brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total gray and white matter perfusion as well as regional gray matter perfusion. Adults 18-30 yr old (females = 22 and males = 26) were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by computational anatomy toolbox (CAT12) analysis in statistical parametric mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females = 62 ± 9 and males = 45 ± 10 mL/100 g/min, P < 0.001), gray matter (females = 75 ± 11 and males = 54 ± 12 mL/100 g/min, P < 0.001), and white matter (females = 44 ± 6 and males = 32 ± 7 mL/100 g/min, P < 0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14% to 66% higher. A second MRI approach (4-dimensional flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, gray, and white matter levels and across dozens of brain regions and offer new clarity into fundamental sex differences in global and regional CBF regulation before aging or pathology.NEW & NOTEWORTHY MRI used to measure cerebral blood flow (CBF) in gray matter, white matter, and 68 regions in healthy men and women. This study demonstrated that CBF is 40% higher in women, the highest sex difference reported, when controlling for numerous important clinical confounders like age, smoking, menstrual cycle, comorbidities, and medications.

A Rose by Any Other Name: Mapping Taxonomic and Thematic Naming Errors Poststroke.

Understanding the neurobiology of semantic knowledge is a major goal of cognitive neuroscience. Taxonomic and thematic semantic knowledge are represented differently within the brain's conceptual networks, but the specific neural mechanisms remain unclear. Some neurobiological models propose that the anterior temporal lobe is an important hub for taxonomic knowledge, whereas the TPJ is especially involved in the representation of thematic knowledge. However, recent studies have provided divergent evidence. In this context, we investigated the neural correlates of taxonomic and thematic confrontation naming errors in 79 people with aphasia. We used three complementary lesion-symptom mapping (LSM) methods to investigate how structure and function in both spared and impaired brain regions relate to taxonomic and thematic naming errors. Voxel-based LSM mapped brain damage, activation-based LSM mapped BOLD signal in surviving tissue, and network-based LSM mapped white matter subnetwork integrity to error type. Voxel- and network-based lesion symptom mapping provided converging evidence that damage/disruption of the left mid-to-anterior temporal lobe was associated with a greater proportion of thematic naming errors. Activation-based lesion symptom mapping revealed that higher BOLD signal in the left anterior temporal lobe during an in-house naming task was associated with a greater proportion of taxonomic errors on the Philadelphia Naming Test administered outside of the scanner. A lower BOLD signal in the bilateral angular gyrus, precuneus, and right inferior frontal cortex was associated with a greater proportion of taxonomic errors. These findings provide novel evidence that damage to the anterior temporal lobe is especially related to thematic naming errors.

Investigating the Mechanisms of Inflammation and Immune Alterations in Parkinson's Disease using Spatial Transcriptomics Techniques

In recent years, overwhelming evidence has emphasized the crucial role of inflammation in the pathogenesis of PD. However, the exact mechanisms by which inflammation damages dopaminergic neurons in PD are still unclear. Therefore, we generated a MPTP-induced PD mouse model and performed spatial transcriptomic sequencing to provide more insight into the process of PD development at specific brain regions. Our results indicate that the pathological changes of PD are mainly manifested in the midbrain, especially in the substantia nigra region, with significant reductions in oligodendrocytes and Agt-labeled astrocytes and an increase in Gfap-labeled astrocytes. Macrophages displayed an increasing trend in the PD environment, indicating a pattern of immune modulation induced by PD. Moreover, pathway analysis revealed significant impairments in ion migration ability, abnormal Ca2+ channels, cAMP signaling, and synaptic damage in PD. Significant downregulation of Mt1 and Mt2 and upregulation of Atp1b2, Gpi1, and Cox6a1 in PD further underscored the occurrence of intense inflammation and immune alterations. On the basis of these findings, we have validated the significant accumulation of Ca2+ in the midbrain tissue in the PD environment by measuring its content. Additionally, we have demonstrated a close association between the reduction of dopaminergic neurons, represented by the midbrain region, and ferroptosis by evaluating the iron content, malondialdehyde (MDA) levels, and the protein expression of GPX4 and TH in the tissue. We propose the hypothesis that PD-related inflammation and immune changes can induce neuronal and oligodendrocyte damage through the induction of ferroptosis, thereby further accelerating the progression of PD.

Repeated LPS induces training and tolerance of microglial responses across brain regions

BackgroundNeuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As the brain’s innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts of peripheral inflammation can trigger long-term changes in microglial gene expression and function, a form of innate immune memory.Methods and resultsIn this study, we used multiple low-dose lipopolysaccharide (LPS) injections in adult mice to study the acute cytokine, transcriptomic, and microglia morphological changes that contribute to the formation of immune memory in the frontal cortex, hippocampus, and striatum, as well as the long-term effects of these changes on behavior. Training and tolerance of gene expression was shared across regions, and we identified 3 unique clusters of DEGs (2xLPS-sensitive, 4xLPS-sensitive, LPS-decreased) enriched for different biological functions. 2xLPS-sensitive DEG promoters were enriched for binding sites for IRF and NFkB family transcription factors, two key regulators of innate immune memory. We quantified shifts in microglia morphological populations and found that while the proportion of ramified and rod-like microglia mostly remained consistent within brain regions and sexes with LPS treatment, there was a shift from ameboid towards hypertrophic morphological states across immune memory states and a dynamic emergence and resolution of events of microglia aligning end-to-end with repeated LPS.ConclusionsTogether, findings support the dynamic regulation of microglia during the formation of immune memories in the brain and support future work to exploit this model in brain disease contexts.

Circadian cilia transcriptome in mouse brain across physiological and pathological states

Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes’ peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts’ oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia’s spatiotemporal dynamics in brain functions.

Motor deficits and brain pathology in the Parkinson’s disease mouse model hA53Ttg

BackgroundParkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of α-synuclein (α-syn) aggregates. The A53T missense point mutation occurs in autosomal dominant familial PD and has been found to promote the aggregation of α-syn. To investigate the role of the A53T mutation in PD, researchers have developed various mouse models with this mutation.ObjectiveWe therefore conducted a comprehensive characterization of the tg(THY1-SNCA*A53T)M53Sud mouse model (hA53Ttg mice) for its motor and pathological features.MethodshA53Ttg mice were tested for motor impairments in a series of motor tests at 2, 4 or 6 months of age. Human α-syn and α-syn pSer129, as well as GFAP and Iba1 signal were labeled and quantified in the cortex, hippocampus, and brainstem. Neurofilament light chain (NF-L) levels were measured in the cerebrospinal fluid (CSF) and plasma. Ex vivo analyses were performed at the age of 2, 4, 6, and 10 months.ResultsBehavioral tests revealed early muscle weakness and motor impairments that progressed with age. Immunohistochemical analyses demonstrated elevated levels of human α-syn and α-syn pSer129 in all evaluated brain regions. α-syn pSer129 labeling further revealed fiber-like structures in the cortex of older animals. Neuroinflammation was observed in an age-dependent manner. Biochemical evaluation revealed elevated NF-L levels in the plasma and CSF. Overall, our findings highlight the value of hA53Ttg mice in modeling PD-associated pathologies that closely resemble those observed in PD patients.ConclusionOur results thus suggest that hA53Ttg mice are a useful tool for studying the underlying mechanisms of PD.

Tetrabenazine, a vesicular monoamine transporter 2 inhibitor, inhibits vesicular storage capacity and release of monoamine transmitters in mouse brain tissue

AbstractBackground and PurposeTetrabenazine (TBZ), used for treating hyperkinetic disorders, inhibits vesicular monoamine transporter‐2 (VMAT‐2), which sequesters monoamines into vesicles for exocytosis. However, our knowledge of the effect of TBZ on monoaminergic transmission is limited. Herein, we provide neurochemical evidence regarding the effect of VMAT‐2 inhibition on vesicular neurotransmitter release from the prefrontal cortex (PFC) and striatum (STR) (brain regions involved in characteristic TBZ treatment side effects). The interaction between TBZ and MDMA was also assessed regarding motor behaviour in mice.Experimental ApproachVesicular storage capacity and release of [3H]‐noradrenaline ([3H]‐NA), [3H]‐dopamine ([3H]‐DA), [3H]‐serotonin ([3H]‐5‐HT), and [3H]‐acetylcholine ([3H]‐ACh) was studied in mouse PFC and STR ex vivo slice preparations using electrical field stimulation. Additionally, locomotor activity was assessed in vehicle‐treated mice and compared with that of MDMA, TBZ, and co‐administered animals (n = 6) using the LABORAS system.Key ResultsTBZ lowered the storage capacity and inhibited the vesicular release of [3H]‐NA and [3H]‐DA from the PFC, and [3H]‐DA and [3H]‐5‐HT from the STR in a concentration‐dependent manner. Unlike vesamicol (vesicular ACh uptake inhibitor), TBZ failed to inhibit the vesicular release of [3H]‐ACh from the PFC. When the vesicular storage of the investigated monoamines was inhibited by TBZ in the PFC and STR, MDMA induced the release of transmitters through transporter reversal; MDMA dose dependently increased locomotor activity in vivo.Conclusion and ImplicationsOur observations provide neurochemical evidence explaining the mechanism of VMAT‐2 inhibitors in the brain and support the involvement of dopaminergic and noradrenergic transmission in hyperkinetic movement disorders.

Association of in vivo retention of [18f] flortaucipir pet with tau neuropathology in corresponding brain regions

[18F]Flortaucipir is an FDA-approved tau-PET tracer that is increasingly utilized in clinical settings for the diagnosis of Alzheimer’s disease. Still, a large-scale comparison of the in vivo PET uptake to quantitative post-mortem tau pathology and to other co-pathologies is lacking. Here, we examined the correlation between in vivo [18F]flortaucipir PET uptake and quantitative post-mortem tau pathology in corresponding brain regions from the AVID A16 end-of-life study (n = 63). All participants underwent [18F]flortaucipir PET scans prior to death, followed by a detailed post-mortem neuropathological examination using AT8 (tau) immunohistochemistry. Correlations between [18F]flortaucipir standardized uptake value ratios (SUVRs) and AT8 immunohistochemistry were assessed across 18 regions-of-interest (ROIs). To assess [18F]flortaucipir specificity and level of detection for tau pathology, correlations between [18F]flortaucipir SUVR and neuritic plaque score and TDP-43 stage were also computed and retention was further assessed in individuals with possible primary age-related tauopathy (PART), defined as Thal phase ≤ 2 and Braak stage I–IV. We found modest-to-strong correlations between in vivo [18F]flortaucipir SUVR and post-mortem tau pathology density in corresponding brain regions in all neocortical regions analyzed (rho-range = 0.61–0.79, p < 0.0001 for all). The detection threshold of [18F]flortaucipir PET was determined to be 0.85% of surface area affected by tau pathology in a temporal meta-ROI, and 0.15% in a larger cortical meta-ROI. No significant associations were found between [18F]flortaucipir SUVRs and post-mortem tau pathology in individuals with possible PART. Further, there was no correlation observed between [18F]flortaucipir and level of amyloid-β neuritic plaque load (rho-range = – 0.16–0.12; p = 0.48–0.61) or TDP-43 stage (rho-range = – 0.10 to – 0.30; p = 0.18–0.65). In conclusion, our in vivo vs post-mortem study shows that the in vivo [18F]flortaucipir PET signal primarily reflects tau pathology, also at relatively low densities of tau proteinopathy, and does not bind substantially to tau neurites in neuritic plaques or in individuals with PART.

InfoFlowNet: A multi-head attention-based self-supervised learning model with surrogate approach for uncovering brain effective connectivity

Deciphering brain network topology can enhance the depth of neuroscientific knowledge and facilitate the development of neural engineering methods. Effective connectivity, which gauges the directional influences among brain regions, is pivotal for these studies. This research introduces InfoFlowNet, a novel self-supervised learning model designed to infer causal relationships in electroencephalogram (EEG) data, aiming at capturing the complex information flow among brain regions. Specifically, InfoFlowNet employs convolution operations and multi-head self-attention mechanisms with a masking feature, which ignores self-connections to focus on inter-regional dynamics. Additionally, a new causal magnitude estimation is introduced by assessing the impact of shuffled surrogate data on signal prediction to quantify causal influence. Experiments using synthetic data and real EEG datasets demonstrate that InfoFlowNet effectively uncovers time-varying causal relationships. Compared with the Granger causality model (GCM) and the temporal causal discovery framework (TCDF), InfoFlowNet shows superior sensitivity in detecting significant causal edges. For instance, in a psychomotor vigilance task, InfoFlowNet identified 8 out of 16 significant causal edges, significantly outperforming GCM and TCDF. Furthermore, InfoFlowNet successfully passes the whiteness test on the model's residuals, and advanced analyses illustrate the advantages of utilizing multi-head attention and masking mechanisms to capture effective connectivity. In sum, InfoFlowNet represents a significant advancement in the analysis of effective connectivity, offering a deeper understanding of brain network dynamics. The model's ability to discern complex causal interactions supports its potential application in broader neuroscientific research and applications.

Role of dorsal striatum circuits in relapse to opioid seeking after voluntary abstinence

AbstractHigh relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABAa and GABAb receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p &lt; 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p &lt; 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p &lt; 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p &lt; 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention.

NMDA receptor antagonist high-frequency oscillations are transmitted via bottom-up feedforward processing

In mammals, NMDA receptor antagonists have been linked to the emergence of high-frequency oscillations (HFO, 130–180 Hz) in cortical and subcortical brain regions. The extent to which transmission of this rhythm is dependent on feedforward (bottom-up) or feedback (top-down) mechanisms is unclear. Previously, we have shown that the olfactory bulb (OB), known to orchestrate oscillations in many brain regions, is an important node in the NMDA receptor-dependent HFO network. Since the piriform cortex (PC) receives major input from the OB, and can modulate OB activity via feedback projections, it represents an ideal site to investigate transmission modalities. Here we show, using silicon probes, that NMDA receptor antagonist HFO are present in the PC associated with current dipoles, although of lower power than the OB. Granger causality and peak-lag analyses implicated the OB as the driver of HFO in the PC. Consistent with this, reversible inhibition of the OB resulted in a reduction of HFO power both locally and in the PC. In contrast, inhibition of the PC had minimal impact on OB activity. Collectively, these findings point to bottom-up mechanisms in mediating the transmission of NMDA receptor antagonist-HFO, at least in olfactory circuits.

Amide proton transfer and apparent diffusion coefficient analysis reveal susceptibility of brain regions to neonatal hypoxic-ischemic encephalopathy

PurposeTo identify brain regions affected by Hypoxic-Ischemic Encephalopathy (HIE) in neonates using Amide Proton Transfer (APT) imaging and Apparent Diffusion Coefficient (ADC). Materials and methodsTwenty neonates were divided into HIE and control groups. All neonates were undergoing MRI, including APT and DWI. Imaging analysis was performed using SPM12. The independent-samples t-test was used to analyze the difference in APTw values and ADC values between the mild HIE neonates and the control group. The receiver operating characteristic (ROC) curves were established to assess the diagnostic values of APTw and ADC values in different brain regions for HIE. Pearson's correlation analysis was used to analyze the correlation between APTw values and ADC values for each region. ResultsAPTw values were significantly higher in 26 regions of the HIE group. ADC values were lower in the right anterior temporal lobe and higher in bilateral Subthalamic nucleus in HIE. The APTw values of 22 regions showed very high area under the curve (AUC), whereas the AUC of ADC values in right anterior temporal lobe and right subthalamic nucleus were both 0.802. Notably, the right anterior temporal lobe exhibited significant differences in both APTw and ADC values between the HIE and control groups, additionally, APTw value was significant positive correlated with ADC values in right anterior temporal lobe. ConclusionAPTw and ADC are effective in detecting HIE, with APTw being more sensitive. The right anterior temporal lobe is particularly affected by HIE, with significant changes in APTw and ADC values and a positive correlation between them. This suggests that temporal lobe damage may be critical in the long-term neurological consequences of HIE.

Estrous cycle-dependent modulation of sexual receptivity in female mice by estrogen receptor beta-expressing cells in the dorsal raphe nucleus

The sexual receptivity of female mice, shown as lordosis response, is mainly regulated by estradiol action on estrogen receptor alpha (ERα) and beta (ERβ), depending on the day of the estrous cycle. Previous studies revealed that ERα in the ventromedial nucleus of the hypothalamus (VMH) plays an essential role in the induction of lordosis on the day of estrus (Day 1). However, the mechanisms of the transition to non-receptive states on the day after estrus (Day 2) are not completely understood. In the present study, we investigated the possible role of ERβ, which is highly expressed in the dorsal raphe nucleus (DRN), in lordosis expression. We found that ERβ-Cre female mice, which were ovariectomized and primed with estradiol and progesterone to mimic the estrous cycle, showed high levels of lordosis on Day 2 when ERβ-expressing DRN (DRN-ERβ+) neuronal activity was chemogenetically suppressed. This finding suggests that excitation of DRN-ERβ+ neurons is necessary for the decline of lordosis on Day 2. Fiber photometry recordings during female-male behavioral interactions revealed that DRN-ERβ+ neuronal activation in response to male intromission was significantly more prolonged on Day 2 compared to Day 1. Chemogenetic over-stimulation of DRN-ERβ+ neurons induced c-Fos expression in brain areas known to be inhibitory for lordosis expression, even though they did not express anterogradely labeled fibers of DRN-ERβ+ cells. These findings collectively suggest that DRN-ERβ+ neuronal excitation serves as an inhibitory modulator and is responsible for the decline in receptivity during non-estrus phases.Significance StatementIn females, switching from a sexually receptive state to a non-receptive phase during the estrous cycle is essential for effective behavioral interactions with males and successful reproduction. Here, we delineate the possible brain regions that regulate the decline in receptive behavioral responses, such as lordosis, from those shown on the day of estrus to those on the day after estrus. We found that excitation of neurons expressing estrogen receptor (ER) β in the midbrain dorsal raphe nucleus is crucial for the suppression of lordosis during the day after estrus. This is contrasted with the facilitatory action of ERα, another type of ER, and provides new insights for understanding the neural basis of the adaptive expression of female reproductive behavior.

Altered static brain activity and functional connectivity after heat stroke.

This study aimed to investigate the alteration of brain function based on resting-state functional MRI in patients after heat stroke. This study included 10 cases of patients after heat stroke and 10 cases of healthy controls. Abnormal brain function was calculated using amplitude of low-frequency fluctuations (ALFF) and degree centrality analysis, as well as functional connectivity analysis based on regions of interest (ROI). Correlation analyses were performed to evaluate the association between brain function changes and clinical scales. Combining ALFF and degree centrality results, the decreased brain regions included the left cuneus and the right angular gyrus, while the increased brain regions included the right cerebellar_Crus1. Using the left cuneus with significant differences in ALFF and degree centrality as ROI, the functional connectivity results revealed decreased brain regions including bilateral lingual gyrus, bilateral postcentral cingulate gyrus, and left precentral gyrus. The degree centrality value of the right cerebellar_Crus1 was positively correlated with glasgow coma scale (GCS) scores (r = 0.726, P = 0.027), and the functional connectivity value of the right posterior cingulate gyrus was positively correlated with GCS scores (r = 0.717, P = 0.030). Heat stroke patients exhibit abnormal activity in multiple brain regions, which has important clinical significance for evaluating the severity of the disease.

Electroencephalography Neurofeedback Training with Focus on the State of Attention: An Investigation Using Source Localization and Effective Connectivity

Identifying brain activity and flow direction can help in monitoring the effectiveness of neurofeedback tasks that aim to treat cognitive deficits. The goal of this study was to compare the neuronal electrical activity of the cortex between individuals from two groups—low and high difficulty—based on a spatial analysis of electroencephalography (EEG) acquired through neurofeedback sessions. These sessions require the subjects to maintain their state of attention when executing a task. EEG data were collected during three neurofeedback sessions for each person, including theta and beta frequencies, followed by a comprehensive preprocessing. The inverse solution based on cortical current density was applied to identify brain regions related to the state of attention. Thereafter, effective connectivity between those regions was estimated using the Directed Transfer Function. The average cortical current density of the high-difficulty group demonstrated that the medial prefrontal, dorsolateral prefrontal, and temporal regions are related to the attentional state. In contrast, the low-difficulty group presented higher current density values in the central regions. Furthermore, for both theta and beta frequencies, for the high-difficulty group, flows left and entered several regions, unlike the low-difficulty group, which presented flows leaving a single region. In this study, we identified which brain regions are related to the state of attention in individuals who perform more demanding tasks (high-difficulty group).

18F-DPA714 PET/MRI as a potential imaging tool for detecting possible antibody-negative autoimmune encephalitis: a prospective study.

Conventional magnetic resonance imaging (MRI) used for detecting possible antibody-negative autoimmune encephalitis (AIE) often fails to meet the diagnostic requirements of this disease. Positron emission tomography (PET) with a translocator protein radioligand can help visualize microglia distribution density in inflammation-related diseases, thereby offering potentially incremental value to conventional MRI for the in vivo assessment of possible antibody-negative AIE. In this prospective study, 15 participants diagnosed with possible antibody-negative AIE and 10 healthy controls were enrolled (ClinicalTrials.gov: NCT05293405, dated March 15, 2022). All participants underwent hybrid 18F-DPA714 PET/MRI and evaluation for modified Rankin scale (mRS) score, clinical assessment scale for AIE (CASE), and appropriate antibodies. A positive finding was defined as the intensity of 18F-DPA714 uptake that was above a threshold of mean standardized uptake value ratio (SUVR) + two standard deviations of SUVR within the corresponding brain regions of healthy controls. The positive detection rate of 18F-DPA714 PET for possible antibody-negative AIE was significantly higher than that of brain MRI (10/15 [67%] vs. 3/15 [20%]; P = 0.039). In addition, both the intensity and extent of 18F-DPA714 uptake were significantly associated with the CASE score (P = 0.002 and 0.001). Meanwhile, SUVR levels in the cerebellar region were significantly higher in patients with ataxia than in those without ataxia (P = 0.006). Furthermore, 18F-DPA714 uptake decreased in 5/10 [50%] patients who underwent follow-up PET/MRI, which mirrored their symptom relief. 18F-DPA714 PET demonstrated its potentially incremental value to conventional MRI for detecting possible antibody-negative AIE.

Investigating Functional Connectivity in Adolescent Depression and Suicide Attempt during Neurofeedback Sessions: A Multivariate Random Covariance Model Approach

Background A recent neurofeedback functional magnetic resonance imaging (NF, fMRI) study on depressed vs. healthy adolescents elicited differential functional connectivity (FC) amongst brain regions of interest (ROIs). Previous results employed univariate methods and included only two seed areas of FC (amygdala and hippocampus). In this study, we propose a new multivariate analysis for whole-network FC estimation. Methods Primary analyses concerned a pre-identified network of 17 salient ROIs reflecting key regions in self-processing and emotion regulation. A random covariance model (RCM) was applied to jointly estimate participant- and group-specific connectivity, where FC was measured by partial correlation conditioned on or adjusted for rest-of-network connectivity patterns. Secondary analyses concerned participant-specific network association with mental functioning changes and the AAL3 whole-brain atlas. Results New findings suggested that depressed adolescents with a suicide attempt expressed significantly higher positive FC between the left temporal gyrus and the left amygdala during NF, compared to negative FC in non-attempting depressed youth, while healthy controls displayed negative FC between the insula, inferior frontal gyrus to inferior parietal lobe connection, compared to mild negative connectivity in depressed adolescents. Previous cross-hemispheric findings in depressed vs. healthy adolescents were corroborated. Conclusion A multivariate RCM uncovered key ROI-pairwise connections differentiating FC patterns between depressed youth vs. healthy controls and among depressed youth, with and without a suicide attempt. Findings were strengthened by enhanced inference vs. univariate methods, and corroboration of previous NF secondary analyses demonstrated future utility for participant-specific study in association with clinical outcomes and/or whole-brain analyses with larger sample sizes.

Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders

BACKGROUND Musical hallucinations (MH) involve the false perception of music in the absence of external stimuli which links with different etiologies. The pathomechanisms of MH encompass various conditions. The etiological classification of MH is of particular importance and offers valuable insights to understand MH, and further to develop the effective treatment of MH. Over the recent decades, more MH cases have been reported, revealing newly identified medical and psychiatric causes of MH. Functional imaging studies reveal that MH activates a wide array of brain regions. An up-to-date analysis on MH, especially on MH comorbid psychiatric conditions is warranted. AIM To propose a new classification of MH; to study the age and gender differences of MH in mental disorders; and neuropathology of MH. METHODS Literatures searches were conducted using keywords such as “music hallucination,” “music hallucination and mental illness,” “music hallucination and gender difference,” and “music hallucination and psychiatric disease” in the databases of PubMed, Google Scholar, and Web of Science. MH cases were collected and categorized based on their etiologies. The t -test and ANOVA were employed (P &lt; 0.05) to compare the age differences of MH different etiological groups. Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed. RESULTS Among the 357 yielded publications, 294 MH cases were collected. The average age of MH cases was 67.9 years, with a predominance of females (66.8% females vs 33.2% males). MH was classified into eight groups based on their etiological mechanisms. Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses. CONCLUSION We carried out a more comprehensive review of MH studies. For the first time according to our knowledge, we demonstrated the psychiatric conditions linked and/or associated with MH from statistical, biological and molecular point of view.

Astrocyte allocation during brain development is controlled by Tcf4-mediated fate restriction

AbstractAstrocytes in the brain exhibit regional heterogeneity contributing to regional circuits involved in higher-order brain functions, yet the mechanisms controlling their distribution remain unclear. Here, we show that the precise allocation of astrocytes to specific brain regions during development is achieved through transcription factor 4 (Tcf4)-mediated fate restriction based on their embryonic origin. Loss of Tcf4 in ventral telencephalic neural progenitor cells alters the fate of oligodendrocyte precursor cells to transient intermediate astrocyte precursor cells, resulting in mislocalized astrocytes in the dorsal neocortex. These ectopic astrocytes engage with neocortical neurons and acquire features reminiscent of dorsal neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during the differentiation of oligodendrocyte precursor cells derived from the ventral telencephalon, thereby restricting the fate to the oligodendrocyte lineage in the dorsal neocortex. Together, our findings highlight a previously unappreciated role for Tcf4 in regulating astrocyte allocation, offering additional insights into the mechanisms underlying neurodevelopmental disorders linked to Tcf4 mutations.