OBJECTIVE: We aimed to investigate mesial temporal lobe abnormalities in mesial temporal lobe epilepsy (MTLE) patients with hypersynchronous (HYP) and low-voltage fast rhythms (LVF) onset identified by stereotactic electroencephalography (SEEG) and evaluate their diagnostic and prognostic value.
METHODS: Fifty-one MTLE patients were categorized as HYP or LVF by SEEG. High-resolution MRI volume-based analysis and 18F-FDG-PET standard uptake values of hippocampal and amygdala subfields were quantified and compared with 57 matched controls. Further analyses were conducted to delineate the distinct pathological characteristics differentiating the two groups. Diagnostic and prognostic prediction performance of these biomarkers were assessed using receiver operating characteristic curves.
RESULTS: LVF-onset individuals demonstrated ipsilateral amygdala enlargement (p = 0.048) and contralateral hippocampus hypermetabolism (p = 0.042), pathological results often accompany abnormalities in the temporal lobe cortex, while HYP-onset subjects had significant atrophy (p < 0.001) and hypometabolism (p = 0.013) in ipsilateral hippocampus and its subfields, as well as amygdala atrophy (p < 0.001), pathological results are highly correlated with hippocampal sclerosis. Severe fimbria atrophy was observed in cases of HYP-onset MTLE with poor prognosis (AUC = 0.874).
CONCLUSIONS: Individuals with different seizure-onset patterns display specific morphological and metabolic abnormalities in the amygdala and hippocampus. Identifying these subfield abnormalities can improve diagnostic and prognostic precision, guiding surgical strategies for MTLE.

UNASSIGNED: Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD).
UNASSIGNED: The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved.
UNASSIGNED: Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed.
UNASSIGNED: Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P < 0.001) and with a shorter time to their development (β = -0.486 [95% CI: -0.62 to -0.35], P < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P < 0.05). Neuro-immune pathways contributed to the development of CVDRFs (P < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression.
UNASSIGNED: Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.

Near-death experience (NDE) is a transcendent mental event of uncertain etiology that arises on the cusp of biological death. Since the discovery of NDE in the mid-1970s, multiple neuroscientific theories have been developed in an attempt to account for it in strictly materialistic or reductionistic terms. Therefore, in this conception, NDE is at most an extraordinary hallucination without any otherworldly, spiritual, or supernatural denotations. During the last decade or so, a number of animal and clinical studies have emerged which reported that about the time of death, there may be a surge of high frequency electroencephalogram (EEG) at a time when cortical electrical activity is otherwise at a very low ebb. This oscillatory rhythm falls within the range of the enigmatic brain wave-labelled gamma-band activity (GBA). Therefore, it has been proposed that this brief, paradoxical, and perimortem burst of the GBA may represent the neural foundation of the NDE. This study examines three separate but related questions concerning this phenomenon. The first problem pertains to the electrogenesis of standard GBA and the extent to which authentic cerebral activity has been contaminated by myogenic artifacts. The second problem involves the question of whether agents that can mimic NDE are also underlain by GBA. The third question concerns the electrogenesis of the surge in GBA itself. It has been contended that this is neither cortical nor myogenic in origin. Rather, it arises in a subcortical (amygdaloid) location but is recorded at the cortex via volume conduction, thereby mimicking standard GBA. Although this surge of GBA contains genuine electrophysiological activity and is an intriguing and provocative finding, there is little evidence to suggest that it could act as a kind of neurobiological skeleton for a phenomenon such as NDE.

OBJECTIVE: Despite the success of presurgical network connectivity studies in predicting short-term (1-year) seizure outcomes, later seizure recurrence occurs in some patients with temporal lobe epilepsy (TLE). To uncover contributors to this recurrence, we investigated the relationship between functional connectivity and seizure outcomes at different time points after surgery in these patients.
METHODS: Patients included were clinically diagnosed with unilateral mesial TLE after a standard clinical evaluation and underwent selective amygdalohippocampectomy. Healthy controls had no history of seizures or head injury. Using resting-state fMRI, we assessed the postsurgical functional connectivity node strength, computed as the node\'s total strength to all other nodes, between seizure-free (Engel Ia-Ib) and nonseizure-free (Engel Ic-IV) acquisitions. The change over time after surgery in different outcome groups in these nodes was also characterized.
RESULTS: Patients with TLE (n = 32, mean age: 43.1 ± 11.9 years; 46.8% female) and 85 healthy controls (mean age: 37.7 ± 13.5 years; 48.2% female) were included. Resting fMRI was acquired before surgery and at least once after surgery in each patient (range 1-4 scans, 5-60 months). Differences between patients with (n = 30) and without (n = 18) seizure freedom were detected in the posterior insula ipsilateral to the resection (I-PIns: 95% CI -154.8 to -50.1, p = 2.8 × 10-4) and the bilateral central operculum (I-CO: 95% CI -163.2 to -65.1, p = 2.6 × 10-5, C-CO: 95% CI -172.7 to -55.8, p = 2.8 × 10-4). In these nodes, only those who were seizure-free had increased node strength after surgery that increased linearly over time (I-CO: 95% CI 1.0-5.2, p = 4.2 × 10-3, C-CO: 95% CI 1.0-5.2, p = 5.5 × 10-3, I-PIns: 95% CI 1.6-5.5, p = 0.9 × 10-3). Different outcome groups were not distinguished by node strength before surgery.
CONCLUSIONS: The findings suggest that network evolution in the first 5 years after selective amygdalohippocampectomy surgery is related to seizure outcomes in TLE. This highlights the need to identify presurgical and surgical conditions that lead to disparate postsurgical trajectories between seizure-free and nonseizure-free patients to identify potential contributors to long-term seizure outcomes. However, the lack of including other surgical approaches may affect the generalizability of the results.

Previous research has established associations between amygdala functional connectivity abnormalities and major depressive disorder (MDD). However, inconsistencies persist due to limited sample sizes and poorly elucidated transcriptional patterns. In this study, we aimed to address these gaps by analyzing a multicenter magnetic resonance imaging (MRI) dataset consisting of 210 first-episode, drug-naïve MDD patients and 363 age- and sex-matched healthy controls (HC). Using Pearson correlation analysis, we established individualized amygdala functional connectivity patterns based on the Automated Anatomical Labeling (AAL) atlas. Subsequently, machine learning techniques were employed to evaluate the diagnostic utility of amygdala functional connectivity for identifying MDD at the individual level. Additionally, we investigated the spatial correlation between MDD-related amygdala functional connectivity alterations and gene expression through Pearson correlation analysis. Our findings revealed reduced functional connectivity between the amygdala and specific brain regions, such as frontal, orbital, and temporal regions, in MDD patients compared to HC. Importantly, amygdala functional connectivity exhibited robust discriminatory capability for characterizing MDD at the individual level. Furthermore, we observed spatial correlations between MDD-related amygdala functional connectivity alterations and genes enriched for metal ion transport and modulation of chemical synaptic transmission. These results underscore the significance of amygdala functional connectivity alterations in MDD and suggest potential neurobiological mechanisms and markers for these alterations.

Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother-infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD\'s neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families.

Normal reproductive function and fertility rely on the rhythmic secretion of gonadotropin-releasing hormone (GnRH), which is driven by the hypothalamic GnRH pulse generator. A key regulator of the GnRH pulse generator is the posterodorsal subnucleus of the medial amygdala (MePD), a brain region that is involved in processing external environmental cues, including the effect of stress. However, the neuronal pathways enabling the dynamic, stress-triggered modulation of GnRH secretion remain largely unknown. Here, we employ in silico modelling in order to explore the impact of dynamic inputs on GnRH pulse generator activity. We introduce and analyse a mathematical model representing MePD neuronal circuits composed of GABAergic and glutamatergic neuronal populations, integrating it with our GnRH pulse generator model. Our analysis dissects the influence of excitatory and inhibitory MePD projections\' outputs on the GnRH pulse generator\'s activity and reveals a functionally relevant MePD glutamatergic projection to the GnRH pulse generator, which we probe with in vivo optogenetics. Our study sheds light on how MePD neuronal dynamics affect the GnRH pulse generator activity and offers insights into stress-related dysregulation.

Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. To investigate this further, we administered a CRFR1 antagonist (CRFR1a), R121919, to young adolescent male and female rats across 4 days. Following each treatment, rats were tested for locomotion, social behavior, mechanical allodynia, or PPI of the acoustic startle reflex. Acute CRFR1 blockade immediately reduced PPI in peripubertal males, but not females. In adulthood, each assay was repeated without CRFR1a exposure to test for long-term effects of the adolescent treatment, with males continuing to experience deficits in PPI, while females displayed altered locomotion, PPI, and social behavior. The amygdala was collected to measure long-term effects on gene expression in pathways related to neural plasticity and neurodevelopmental disorders. Relative expression of cannabinoid type 1 receptors (CB1R), which mediate sensorimotor and HPA function, was also measured. In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males and lower expression of CB1R protein in females. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for adolescent psychiatric treatment protocols.

UNASSIGNED: Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.
UNASSIGNED: C57BL/6J mice were infected with 10 cysts of T. gondii. Antibiotic depletion of gut microbiota and fecal microbiota transplantation experiments were utilized to investigate the causal relationship between gut microbiota and anxiety. Anxiety-like behaviors were examined by the elevated plus maze test and the open field test; blood, feces, colon and amygdala were collected to evaluate the profiles of serum endotoxin (Lipopolysaccharide, LPS) and serotonin (5-hydroxytryptamine, 5-HT), gut microbiota composition, metabolomics, global transcriptome and neuroinflammation in the amygdala. Furthermore, the effects of Diethyl butylmalonate (DBM, an inhibitor of mitochondrial succinate transporter, which causes the accumulation of endogenous succinate) on the disorders of the gut-brain axis were evaluated.
UNASSIGNED: Here, we found that T. gondii chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the amygdala, T. gondii infection triggered the microglial activation and neuroinflammation. In the colon, T. gondii infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, T. gondii infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by T. gondii infection. More importantly, transplantation of the fecal microbiota from T. gondii-infected mice resulted in anxiety and the transcriptomic alteration in the amygdala of the antibiotic-pretreated mice. Notably, the decreased abundance of succinate-producing bacteria and the decreased production of succinate were observed in the feces of the T. gondii-infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by T. gondii infection.
UNASSIGNED: The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic T. gondii infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of T. gondii-related mental disorders.

The human brain is sensitive to threat-related information even when we are not aware of this information. For example, fearful faces attract gaze in the absence of visual awareness. Moreover, information in different sensory modalities interacts in the absence of awareness, for example, the detection of suppressed visual stimuli is facilitated by simultaneously presented congruent sounds or tactile stimuli. Here, we combined these two lines of research and investigated whether threat-related sounds could facilitate visual processing of threat-related images suppressed from awareness such that they attract eye gaze. We suppressed threat-related images of cars and neutral images of human hands from visual awareness using continuous flash suppression and tracked observers\' eye movements while presenting congruent or incongruent sounds (finger snapping and car engine sounds). Indeed, threat-related car sounds guided the eyes toward suppressed car images, participants looked longer at the hidden car images than at any other part of the display. In contrast, neither congruent nor incongruent sounds had a significant effect on eye responses to suppressed finger images. Overall, our results suggest that only in a danger-related context semantically congruent sounds modulate eye movements to images suppressed from awareness, highlighting the prioritisation of eye responses to threat-related stimuli in the absence of visual awareness.