Our brains create new memories by capturing the \'who/what\', \'where\' and \'when\' of everyday experiences. On a neuronal level, mechanisms facilitating a successful transfer into episodic memory are still unclear. We investigated this by measuring single neuron activity in the human medial temporal lobe during encoding of item-location associations. While previous research has found predictive effects in population activity in human MTL structures, we could attribute such effects to two specialized sub-groups of neurons: concept cells in the hippocampus, amygdala and entorhinal cortex (EC), and a second group of parahippocampal location-selective neurons. In both item- and location-selective populations, firing rates were significantly higher during successfully encoded trials. These findings are in line with theories of hippocampal indexing, since selective index neurons may act as pointers to neocortical representations. Overall, activation of distinct populations of neurons could directly support the connection of the \'what\' and \'where\' of episodic memory.

BACKGROUND: High psychological stress has been associated with several brain functional changes, including functional connectivity (FC) alterations in regions such as the prefrontal cortex and the amygdala. This study explored FC alterations associated with high perceived stress, and also investigated whether these neuroimaging features were correlated with low levels of mindfulness.
METHODS: This study included 29 adults (12 males and 17 females; mean age: 27.6 ± 3.2) who complained of moderate or higher perceived stress and 31 adults (17 males and 14 females; mean age: 29.2 ± 7.2) who complained of low-level stress on the questionnaire scale. Seed-based resting-state FC analysis was conducted to compare between high and low stress groups. The dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (VMPFC) and the amygdala were selected as seeds.
RESULTS: High stress group showed weaker left amygdala-based FC in the left cerebellum crus II and the left orbitofrontal cortex compared with low stress group. High stress group had weaker FC between the left DLPFC and the left inferior parietal lobule. On the contrary, high stress group had stronger FC between the left VMPFC and the left caudate compared with low stress group. Weaker FC between the amygdala and the cerebellum crus II was correlated with lower level of awareness facet of mindfulness.
CONCLUSIONS: Those with high perceived stress showed low levels of mindfulness and several FC alterations centered on the prefrontal cortex and amygdala. Our findings also suggest that weak amygdala-based FC alterations associated with high psychological stress are related to low-level awareness facet of mindfulness.

This case-control study assesses associations of amygdala cannabinoid 1 receptor availability with amygdala response to shock-induced pain and severity of emotional numbing symptoms of veterans with posttraumatic stress disorder.

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.

Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2,000µg, 1,000µg, and 1,000µg oral to the dam respectively) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional behaviors of relevance to neurodevelopmental disorders.

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.

By establishing semaphorin 6D expression in the amygdala as a central coordinator of brain, metabolic, and immunologic function, the Neuron publication by Nakanishi et al.1 provides new insight to how primary brain deficiency impacts physiological systems beyond the brain.

It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.

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.