Associations between parental rearing style and amygdala and hippocampal subfield abnormalities in drug-naive females with anorexia nervosa.

BACKGROUND: Altered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics. METHODS: This study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics. RESULTS: AN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference. CONCLUSION: This study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

The volumes of amygdala subregions and peripheral programmed cell death protein-1 levels are associated with cognitive decline in individuals with knee osteoarthritis.

BACKGROUND: Persistent pain is a prominent symptom of knee osteoarthritis (KOA) and has been associated with cognitive decline in individuals with KOA. The amygdala, a complex structure consisting of nine subnuclei, and programmed cell death protein-1 (PD-1) levels play crucial roles in pain regulation and cognitive processing. This study aims to investigate the relationships among amygdala subregion volumes, cognitive function, and PD-1 levels to elucidate the underlying mechanism of cognitive decline in KOA. METHODS: In this cross-sectional study, we recruited 36 patients with KOA and 25 age/gender-matched healthy controls for neuropsychological tests, structural magnetic resonance imaging scanning, and measurement of serum PD-1 levels. We used the atlas provided by FreeSurfer software to automatically segment the amygdala subnuclei. Subsequently, we compared the volumes of amygdala subregions between groups and explored their correlation with clinical scores and PD-1 levels. RESULTS: Compared to healthy controls, individuals with KOA exhibited significantly lower scores on global cognition tasks, such as long-delay free recall, short-delay free recall, and immediate recall tasks. Moreover, they displayed decreased volumes in lateral nucleus basal nucleus paralaminar nucleus while showing increased volumes in accessory basal nucleus, central nucleus, medial nucleus, and cortical nucleus. Within the KOA group specifically, paralaminar volume was negatively correlated with immediate recall scores; pain scores were negatively correlated with global cognition; basal volume was negatively correlated with PD-1 levels. CONCLUSION: Our findings highlight those alterations in amygdala subregion volumes along with changes in serum PD-1 levels may contribute to observe cognitive decline among individuals suffering from KOA.

Distinct medial amygdala oxytocin receptor neurons projections respectively control consolation or aggression in male mandarin voles.

The individuals often show consolation to distressed companions or show aggression to the intruders. The circuit mechanisms underlying switching between consolation and aggression remain unclear. In the present study, using male mandarin voles, we identified that two distinct subtypes of oxytocin receptor (OXTR) neurons in the medial amygdala (MeA) projecting to the anterior insula (AI) and ventrolateral aspect of ventromedial hypothalamus (VMHvl) response differently to stressed siblings or unfamiliar intruders using c-Fos or calcium recording. Oxytocin release and activities of PVN neurons projecting to MeA increased upon consoling and attacking. OXTR antagonist injection to the MeA reduced consoling and attacking. Apoptosis, optogenetic or pharmacogenetic manipulation of these two populations of neurons altered behavioral responses to these two social stimuli respectively. Here, we show that two subtypes of OXTR neurons in the MeA projecting to the AI or VMHvl causally control consolation or aggression that may underlie switch between consolation and aggression.

Disrupted basolateral amygdala circuits supports negative valence bias in depressive states.

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

Association between subcortical nuclei volume changes and cognition in preschool-aged children with tetralogy of Fallot after corrective surgery: a cross-sectional study.

BACKGROUND: Neurocognitive disorders frequently occur in patients with cyanotic congenital heart disease (CCHD) because of the hemodynamic abnormalities induced by preoperative cardiac structural changes. We aimed to evaluate subcortical nuclei volume changes and cognition in postoperative tetralogy of Fallot (TOF) children, and analyze their relationship with preoperative cardiac structural changes. METHODS: This case-control study involved thirty-six children with repaired TOF and twenty-nine healthy controls (HCs). We utilized three-dimensional (3D) T1-weighted high-resolution structural images alongside the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) to evaluate the cognitive differences between the TOF and HC group. RESULTS: We observed notable differences in subcortical nuclei volume between the TOF and HC group, specifically in the left amygdala nucleus (LAM, TOF: 1292.60 ± 155.57; HC: 1436.27 ± 140.62, p < 0.001), left thalamus proper nucleus (LTHA, TOF: 6771.54 ± 666.03; HC: 7435.36 ± 532.84, p < 0.001), and right thalamus proper nucleus (RTHA, TOF: 6514.61 ± 715.23; HC: 7162.94 ± 554.60, p < 0.001). Furthermore, a diminished integrity of LAM ( ß:-19.828, 95% CI: -36.462, -3.193), which showed an inverse relationship with the size of the preoperative ventricular septal defect (VSD), correlated with lower working memory indices in children with TOF. CONCLUSIONS: Our findings indicate that subcortical nuclei structural injuries possibly potentially stemming from cardiac anatomical abnormalities, are associated with impaired working memory in preschool-aged children with TOF. The LAM in particular may serve as a potential biomarker for neurocognitive deficits in TOF, offering predictive value for future neurodevelopmental outcomes, and shedding light on the neurophysiological mechanisms of these cognitive impairments.

Concept and location neurons in the human brain provide the 'what' and 'where' in memory formation.

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.

Bilateral connections from the amygdala to extrastriate visual cortex in the marmoset monkey.

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.

Impacts beyond the brain: Unraveling molecular mechanisms linking psychiatric, metabolic, and inflammatory conditions.

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.

Association Between Postsurgical Functional Connectivity and Seizure Outcome in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: 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. DISCUSSION: 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.

Activation of NPY2R-expressing amygdala neurons inhibits itch behavior in mice without lateralization.

The central amygdala (CeA) is a crucial hub in the processing of affective itch, containing a diverse array of neuronal populations. Among these components, Neuropeptide Y (NPY) and its receptors, such as NPY2R, affect various physiological and psychological processes. Despite this broad impact, the precise role of NPY2R+ CeA neurons in itch modulation remains unknown, particularly concerning any potential lateralization effects. To address this, we employed optogenetics to selectively stimulate NPY2R+ CeA neurons in mice, investigating their impact on itch modulation. Optogenetic activation of NPY2R+ CeA neurons reduced scratching behavior elicited by pruritogens without exhibiting any lateralization effects. Electrophysiological recordings confirmed increased neuronal activity upon stimulation. However, this modulation did not affect thermal sensitivity, mechanical sensitivity, or formalin-induced hyperalgesia. Additionally, no alterations in anxiety-like behaviors or locomotion were observed upon stimulation. Projection tracing revealed connections of NPY2R+ CeA neurons to brain regions implicated in itch processing. Overall, this comprehensive study highlights the role of NPY2R+ CeA neurons in itch regulation without any lateralization effects.

Excessive hydrogen sulfide-induced activation of NMDA receptors in the colon participates in anxiety- and compulsive-like behaviors in a rodent model of hemorrhagic shock and resuscitation.

OBJECTIVE: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H2S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H2S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function. METHODS: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H2S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. RESULTS: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. CONCLUSION: This experimental data suggests that H2S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.

Transdiagnostic depression severity and its relationship to global and prefrontal-amygdala structural properties in people with major depression and post-traumatic stress disorder.

While some studies have used a transdiagnostic approach to relate depression to metabolic or functional brain alterations, the structural substrate of depression across clinical diagnostic categories is underexplored. In a cross-sectional study of 52 patients with major depressive disorder and 51 with post-traumatic stress disorder, drug-naïve, and spanning mild to severe depression severity, we examined transdiagnostic depressive correlates with regional gray matter volume and the topological properties of gray matter-based networks. Locally, transdiagnostic depression severity correlated positively with gray matter volume in the right middle frontal gyrus and negatively with nodal topological properties of gray matter-based networks in the right amygdala. Globally, transdiagnostic depression severity correlated positively with normalized characteristic path length, a measure implying brain integration ability. Compared with 62 healthy control participants, both major depressive disorder and post-traumatic stress disorder patients showed altered nodal properties in regions of the fronto-limbic-striatal circuit, and global topological organization in major depressive disorder in particular was characterized by decreased integration and segregation. These findings provide evidence for a gray matter-based structural substrate underpinning depression, with the prefrontal-amygdala circuit a potential predictive marker for depressive symptoms across clinical diagnostic categories.

Amygdala Cannabinoid 1 Receptor, Pain Response, and Emotional Numbing in Trauma-Exposed Individuals.

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.

Delineating structural and metabolic abnormalities in amygdala and hippocampal subfields for different seizure-onset patterns via stereotactic electroencephalography.

AIMS: 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). CONCLUSION: 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.

Hippocampal and limbic microstructure changes associated with stress across the lifespan: a UK biobank study.

Experiencing highly stressful events can have detrimental and lasting effects on brain morphology. The current study explores the effects of stress during childhood and adulthood on grey matter macro- and microstructure using a sub-sample of 720 participants from the UK Biobank with very high or very low childhood and adulthood stress scores. We used T1-weighted and diffusion MRI data to assess grey matter macro- and microstructure within bilateral hippocampus, amygdala and thalamus. Findings showed that childhood stress is associated with changes in microstructural measures bilaterally within the hippocampus and amygdala. No effects of adulthood stress on brain microstructure were found. No interaction effects between sex and stress (either childhood or adulthood) were observed for any brain imaging measure. Analysis of sub-segments of the hippocampus showed that childhood stress predominantly impacted the bilateral heads of the hippocampus. Overall, these findings suggest that highly stressful experiences during childhood, but not adulthood, have lasting impact on brain microstructure. The effects of these experiences in childhood appear to persist regardless of experiences of high or low stress in adulthood.

Amygdala connectivity is associated with withdrawn/depressed behavior in a large sample of children from the Adolescent Brain Cognitive Development (ABCD) Study®.

Many psychopathologies tied to internalizing symptomatology emerge during adolescence, therefore identifying neural markers of internalizing behavior in childhood may allow for early intervention. We utilized data from the Adolescent Brain and Cognitive Development (ABCD) Study® to evaluate associations between cortico-amygdalar functional connectivity, polygenic risk for depression (PRSD), traumatic events experienced, internalizing behavior, and internalizing subscales: withdrawn/depressed behavior, somatic complaints, and anxious/depressed behaviors. Data from 6371 children (ages 9-11) were used to analyze amygdala resting-state fMRI connectivity to Gordon parcellation based whole-brain regions of interest (ROIs). Internalizing behaviors were measured using the parent-reported Child Behavior Checklist. Linear mixed-effects models were used to identify patterns of cortico-amygdalar connectivity associated with internalizing behaviors. Results indicated left amygdala connections to auditory, frontoparietal network (FPN), and dorsal attention network (DAN) ROIs were significantly associated with withdrawn/depressed symptomatology. Connections relevant for withdrawn/depressed behavior were linked to social behaviors. Specifically, amygdala connections to DAN were associated with social anxiety, social impairment, and social problems. Additionally, an amygdala connection to the FPN ROI and the auditory network ROI was associated with social anxiety and social problems, respectively. Therefore, it may be important to account for social behaviors when looking for brain correlates of depression.

Gut microbiota mediates anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Neural correlates of anhedonia in young adults with subthreshold depression: A graph theory approach for cortical-subcortical structural covariance.

BACKGROUND: Anhedonia is an enduring symptom of subthreshold depression (StD) and predict later onset of major depressive disorder (MDD). Brain structural covariance describes the inter-regional distribution of morphological changes compared to healthy controls (HC) and reflects brain maturation and disease progression. We investigated neural correlates of anhedonia from the structural covariance. METHODS: T1-weighted brain magnetic resonance images were acquired from 79 young adults (26 StD, 30 MDD, and 23 HC). Intra-individual structural covariance networks of 68 cortical surface area (CSAs), 68 cortical thicknesses (CTs), and 14 subcortical volumes were constructed. Group-level hubs and principal edges were defined using the global and regional graph metrics, compared between groups, and examined for the association with anhedonia severity. RESULTS: Global network metrics were comparable among the StD, MDD, and HC. StD exhibited lower centralities of left pallidal volume than HC. StD showed higher centralities than HC in the CSAs of right rostral anterior cingulate cortex (ACC) and pars triangularis, and in the CT of left pars orbitalis. Less anhedonia was associated with higher centralities of left pallidum and right amygdala, higher edge betweenness centralities in the structural covariance (EBSC) of left postcentral gyrus-parahippocampal gyrus and LIPL-right amygdala. More anhedonia was associated with higher centralities of left inferior parietal lobule (LIPL), left postcentral gyrus, left caudal ACC, and higher EBSC of LIPL-left postcentral gyrus, LIPL-right lateral occipital gyrus, and left caudal ACC-parahippocampal gyrus. LIMITATIONS: This study has a cross-sectional design. CONCLUSIONS: Structural covariance of brain morphologies within the salience and limbic networks, and among the salience-limbic-default mode-somatomotor-visual networks, are possible neural correlates of anhedonia in depression.

A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice.

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons regulate fertility and integrate hormonal status with environmental cues to ensure reproductive success. Here we show that GnRH neurons in the olfactory bulb (GnRHOB) of adult mice can mediate social recognition. Specifically, we show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the median eminence. GnRHOB neurons in males express vomeronasal and olfactory receptors, are activated by female odors and mediate gonadotropin release in response to female urine. Male preference for female odors required the presence and activation of GnRHOB neurons, was impaired after genetic inhibition or ablation of these cells and relied on GnRH signaling in the posterodorsal medial amygdala. GnRH receptor expression in amygdala kisspeptin neurons appear to be required for GnRHOB neurons' actions on male mounting behavior. Taken together, these results establish GnRHOB neurons as regulating fertility, sex recognition and mating in male mice.

Distinct homotopic functional connectivity patterns of the amygdalar sub-regions as biomarkers in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). METHOD: Sixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. RESULTS: Patients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = -0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. LIMITATIONS: The current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. CONCLUSIONS: Using a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.