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Background: Depression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma)., Methods: At baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory- Second Edition (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected)., Results: Greater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma., Limitations: The small sample size, limited depression severity, and seed-based approach are limitations., Conclusions: The associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Published by Elsevier B.V.)

Due to the similarities in behavioral characteristics between romantic love and addictive disorders, the concept of being "addicted to someone" transcends mere literary metaphor, expanding perspectives on the study of romantic love and inspiring interventions for addiction. However, there has been a lack of studies systematically exploring the similarities and differences between romantic love and addiction at the neural level. In this study, we conducted an extensive literature search, incorporating 21 studies on romantic love and 28 on addictive disorders, focusing on fMRI research utilizing the cue reactivity paradigm. Using Activation Likelihood Estimation, we examined the similarities and differences in the neural mechanisms underlying love and addiction. The results showed that the anterior cingulate cortex (ACC) exhibited both shared and distinct activation clusters between romantic love and addictive disorders. Furthermore, ventromedial prefrontal cortex (VMPFC) was more frequently activated in romantic love than in addictive disorders, while greater activation within the posterior cingulate cortex (PCC) was found in addictive disorder compared with romantic love. We discussed that the activation of ACC and VMPFC may symbolize self-expansion, a process that characterizes the development of romantic love, contributing to a more enriched self. Our study suggests that while romantic love and addictive disorders share a common neural foundation, the discernible differences in their neural representations distinguish them as joyful growth versus compulsive hedonism., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aims to elucidate the neuroimaging changes associated with major depressive disorder (MDD) and their relationship with genetic characteristics. We conducted a global-brain functional connectivity (GFC) and genetic-neuroimaging correlation analysis on 42 MDD patients and 42 healthy controls (HCs), exploring the correlation between GFC abnormalities and clinical variables. Results showed that compared to HCs, MDD patients had significantly decreased GFC values in the bilateral posterior cingulate cortex/precuneus and increased GFC values in the left and right cerebellum Crus I/II. Additionally, a negative correlation was observed between the GFC values of the left cerebellum Crus I/II and subjective support scores, as well as social support revalued scale total scores. We identified genes associated with GFC changes in MDD, which are enriched in biological processes such as synaptic transmission and ion transport. Our findings indicate the presence of abnormal GFC values in severe depression, complementing the pathological research on the condition. Furthermore, this study provides preliminary evidence for the correlation between social support levels and brain functional connectivity, offering insights into the potential association between GFC changes and gene expression in MDD patients.

Background: Cannabidiol (CBD) impacts brain regions implicated in anxiety reactivity and stress reactivity (e.g., amygdala, anterior cingulate cortex (ACC), anterior insula (AI)); however, placebo-controlled studies are mixed regarding CBD's anxiolytic effects. We previously reported that CBD expectancy alone can alter subjective, physiological, and endocrine markers of stress/anxiety; however, it is unclear whether these findings reflect altered brain reactivity. This study evaluated whether CBD expectancy independently alters amygdala resting-state functional connectivity (rsFC) with the ACC and AI following acute stress., Method: Thirty-eight (20 females) healthy adults were randomly assigned to receive accurate or inaccurate information regarding the CBD content of a CBD-free oil administered during a single experimental session. Following a baseline resting state MRI scan, participants administered their assigned oil sublingually, engaged in a stress task (serial subtraction with negative feedback) inside the scanner, and underwent another resting state MRI scan. Amygdala rsFC with the ACC and AI was measured during each scan, and the subjective state was assessed at six time points. Outcomes were analyzed using ANCOVA., Results: CBD expectancy (vs CBD-free expectancy) was associated with significantly weaker rsFC between the left amygdala and right ACC ( p  = 0.042), but did not systematically alter amygdala-AI rsFC ( p- values > 0.05). We also replicated our previously reported CBD expectancy effects on subjective stress/anxiety in the scanner context., Conclusion: CBD placebo effects may be sufficient to alter neural responses relevant to its purported anxiolytic and stress-relieving properties. Future work is needed to replicate these results and determine whether CBD expectancy and pharmacology interact to alter neural anxiety reactivity and stress reactivity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics., Methods: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data., Results: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years., Conclusion: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chronic insomnia disorder (CID) is commonly associated with mood disorders. The cingulate gyrus (CG) plays a critical role in the pathophysiology of CID and anxiety. However, the specific characteristics of altered brain networks in the CG in CID with anxiety remain unclear. This study aimed to investigate the characteristics of CG functional connectivity (FC) in CID with and without anxiety., Methods: Resting-state functional magnetic resonance imaging was conducted on 92 CID and 36 healthy controls (HC). CID was divided into CID with anxiety (CID-A, N = 37) and CID without anxiety (CID-NA, N = 55) groups based on anxiety scores. Using the Human Brainnetome Atlas, the subregion CG FC network was constructed., Results: Compared with HC, CID showed significantly decreased CG FC with the precuneus, middle frontal gyrus (MFG), and hippocampus, while showing significantly increased CG FC with the middle temporal gyrus (MTG)/superior temporal gyrus (STG). In contrast, CID-A showed significantly decreased CG FC with the salience network (insular, putamen) and default mode network (MTG/STG and inferior parietal lobule), while showing significantly increased CG FC with the thalamus and MFG compared to CID-NA. Further, CID-A and CID-NA could be classified with 84.21 % accuracy by using the CG FCs as features. Among these features, the CG FC with MFG, thalamus, and putamen had the highest contribution weights., Conclusion: This study revealed specific changes in the brain network of the CG subregion in CID-A. Understanding these CG FC alterations can help identify potential biomarkers specific to CID-A, which may be valuable for early detection and differentiation from other CID subtypes., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The study aims to analyze alterations in dynamic functional connectivity density (dFCD) and effective connectivity (dEC) patterns using functional magnetic resonance imaging (fMRI), hypothesizing that overactive bladder (OAB) patients will exhibit distinct dFCD and dEC patterns, reflecting altered neural communication underlying the OAB., Methods: Forty-three female OAB patients and 40 female healthy controls (HC) underwent resting-state fMRI. Sliding window correlation was used to calculate the variability of the dFCD. The changes in dFCD-based dEC between the two groups were examined using Granger causal analysis. To describe the time-varying Granger causality, a sliding-window approach was utilized to divide time courses into a group of windows. We adopted a k-means clustering method to cluster all matrices into discrete connectivity states., Results: Compared with HC, OAB females consistently had a dFCD (decreased) in the left anterior cingulate cortex (ACC) and left medial prefrontal cortex (mPFC) (p < 0.05, GRF corrected). In state 1, OAB patients had excitatory effective connections from bilateral ACC to left mPFC in comparison to HC. In state 2, there was an increase in dEC from the SMA to the mPFC. Participants with OAB showed significantly more inhibitory dorsolateral prefrontal cortex (dlPFC) connections between the left ACC and the right ACC in state 4, as well as an excitatory dEC connection between the right dlPFC and the left ACC in state 2 (p < 0.05, GRF corrected)., Conclusion: OAB patients demonstrate significant alterations in dFCD and dEC patterns, which may be indicative of the neural mechanisms involved in OAB pathophysiology., (© 2024 Wiley Periodicals LLC.)

Abstract: The anterior cingulate cortex (ACC) plays a crucial role in the perception of pain. It is consistently activated by noxious stimuli and its hyperactivity in chronic pain indicates plasticity in the local neuronal network. However, the way persistent pain effects and modifies different neuronal cell types in the ACC and how this contributes to sensory sensitization is not completely understood. This study confirms the existence of 2 primary subtypes of pyramidal neurons in layer 5 of the rostral, agranular ACC, which we could classify as intratelencephalic (IT) and cortico-subcortical (SC) projecting neurons, similar to other cortical brain areas. Through retrograde labeling, whole-cell patch-clamp recording, and morphological analysis, we thoroughly characterized their different electrophysiological and morphological properties. When examining the effects of peripheral inflammatory pain on these neuronal subtypes, we observed time-dependent plastic changes in excitability. During the acute phase, both subtypes exhibited reduced excitability, which normalized to pre-inflammatory levels after day 7. Daily conditioning with nociceptive stimuli during this period induced an increase in excitability specifically in SC neurons, which was correlated with a decrease in mechanical sensitization. Subsequent inhibition of the activity of SC neurons projecting to the periaqueductal gray with in vivo chemogenetics, resulted in reinstatement of the hypersensitivity. Accordingly, it was sufficient to enhance the excitability of these neurons chemogenetically in the inflammatory pain condition to induce hypoalgesia. These findings suggest a cell type-specific effect on the descending control of nociception and a cellular mechanism for pain-induced analgesia. Furthermore, increased excitability in this neuronal population is hypoalgesic rather than hyperalgesic., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment., Methods: Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed., Results: BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group., Limitations: All female samples., Discussion: Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection., Competing Interests: Declaration of competing interest JJM and BHS receive royalties from the Research Foundation for Mental Hygiene for commercial use of the C-SSRS. CAM, NS, BSB, and KNO have no conflicts to report. The design, preparation, review, and approval of the manuscript as well as the decision to submit the manuscript for publication was entirely done by the authors CAM, NS, BSB, KNO, JJM, and BHS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke., Methods: We enrolled people who had experienced their first ischemic stroke, along with healthy controls. We assessed empathy 3 months after stroke using the Chinese version of the Empathy Quotient (EQ). During the acute phase, all patients underwent basic magnetic resonance imaging (MRI), followed by multimodal MRI during follow-up. Our MRI analyses encompassed acute infarction segmentation, volumetric brain measurements, regional quantification of diffusion parameters, and both region-of-interest-based and seed-based functional connectivity assessments. We grouped patients based on the severity of their empathy impairment for comparative analysis., Results: We included 84 patients who had stroke and 22 healthy controls. Patients had lower EQ scores than controls. Patients with low empathy had larger left cortical infarcts (odds ratio [OR] 4.082, 95% confidence interval [CI] 1.183-14.088), more pronounced atrophy in the right cingulate cortex (OR 1.248, 95% CI 1.038-1.502), and lower scores on the Montreal Cognitive Assessment (OR 0.873, 95% CI 0.74-0.947). In addition, the cingulate cortex served as the seed in the seed-based analysis, which showed heightened functional connectivity between the anterior cingulate gyrus and the right superior parietal lobule, specifically in the low-empathy group., Limitations: We did not evaluate the relationship between specific network involvement and empathy impairment among patients following stroke., Conclusion: Among patients with subacute ischemic stroke, reduced empathy was strongly associated with a more severe cognitive profile and atrophy of the right cingulate cortex. Our subsequent structural-informed functional MRI analysis suggests that the enhanced connectivity between the anterior cingulate gyrus and the superior parietal lobule may function as a compensatory mechanism for this atrophy., Competing Interests: Competing interests:: Yi-Shan Luo is employed by BrainNow Medical Technology Limited. Lin Shi is the director of BrainNow Medical Technology. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Pain emotion is a negative emotion caused by pain, which seriously affects the patients' physical and psychological health. The anterior cingulate cortex (ACC) is a key brain region in the occurrence and regulation of pain and painful emotion. In this paper, we summed up the relevant progress of researches on acupuncture improvement of pain emotion from neurotransmitters and receptors, cellular signaling pathways and neural circuits of ACC, in order to provide a basis for further research. 1) Acupuncture can regulate the long-term potentiation of ACC synaptic transmission by down-regulating the expression of N-methyl-D-aspartic acid receptor (NMDAR)； and up-regulating the expression of μ-, delta- and κ-opioid receptors, neuropeptide S (NPS)/ NPS receptor, and the number of parvalbumin-expressing interneurons to reduce neuronal excitability, relieving pain emotion； 2) Acupuncture can regulate synaptic transmission of ACC neurons by inhibiting protein kinase Mζ (PKMζ)-GluR1 and cAMP/PKA-ERK-CREB signaling pathways, and modulate synaptic plasticity to ameliorate pain emotion； 3) Acupuncture intervention induced inhibition of rostral ACC Glu -thalamic circuit may result in relief of pain emotion but not pain sensation, whereas inhibition of the rostral ACC Glu -ventrolateral periaqueductal gray matter(vlPAG) circuit may relieve pain sensation but not pain emotion. In addition, our team found that in the treatment of painful diseases by acupuncture, the addition of "spirit-regulating" acupoints can not only improve patients' negative emotion, but also significantly relive patients' pain sensation.

Alzheimer's disease (AD) encompasses a long continuum from a preclinical phase, characterized by neuropathological alterations albeit normal cognition, to a symptomatic phase, marked by its clinical manifestations. Yet, the neural mechanisms responsible for cognitive decline in AD patients remain poorly understood. Here, we posit that anosognosia, emerging from an error-monitoring failure due to early amyloid-β deposits in the posterior cingulate cortex, plays a causal role in the clinical progression of AD by preventing patients from being aware of their deficits and implementing strategies to cope with their difficulties, thus fostering a vicious circle of cognitive decline., (© 2024. The Author(s).)

Inflammatory bowel diseases (IBD) are a group of chronic, non-specific intestinal diseases that could comorbid with varieties of negative emotional constructs, including pain-related negative emotions and trait negative emotions; however, the link between brain functions and different dimensions of negative emotions remains largely unknown. Ninety-eight patients with IBD and forty-six healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. The amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were used to assess resting-state brain activity. Partial least squares (PLS) correlation was employed to assess the relationship among abnormal brain activities, pain-related and trait negative emotions. Compared to controls, patients with IBD exhibited higher values of ALFF in the right anterior cingulate cortex (ACC), lower values of ALFF in the left postcentral gyrus, and higher values of DC in the bilateral ACC. Multivariate PLS correlation analysis revealed the brain scores of the ACC were correlated with pain-related negative emotions, the brain salience in the left postcentral gyrus was associated with the higher-order trait depression. These findings can enhance our comprehension of how pain-related negative emotion and trait negative emotion affect the brains of patients with IBD in distinct ways., (© 2024. The Author(s).)

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Sleep disruption and negative affect are attendant features of many psychiatric and neurological conditions that are often co-morbid including major depressive disorder, generalized anxiety disorder and chronic pain. Whether there is a causal relationship between negative affect and sleep disruption remains unclear. We therefore asked if mechanisms promoting negative affect can disrupt sleep and whether inhibition of pathological negative affect can normalize disrupted sleep. Signaling at the kappa opioid receptor (KOR) elicits dysphoria in humans and aversive conditioning in animals. We tested the possibility that (a) increased KOR signaling in the anterior cingulate cortex (ACC), a brain region associated with negative emotions, would be sufficient to promote both aversiveness and sleep disruption and (b) inhibition of KOR signaling would normalize pathological negative affect and sleep disruption induced by chronic pain. Chemogenetic Gi-mediated inhibition of KOR-expressing ACC neurons produced conditioned place aversion (CPA) as well as sleep fragmentation in naïve mice. CRISPR/Cas9 editing of ACC KOR normalized both the negative affect and sleep disruption elicited by pathological chronic pain while maintaining the physiologically critical sensory features of pain. These findings suggest therapeutic utility of KOR antagonists for treatment of disease conditions that are associated with both negative affect and sleep disturbances., (© 2024. The Author(s).)

The anterior cingulate cortex (ACC) is one of the critical brain areas for processing noxious information. Previous studies showed that peripheral nerve injury induced broad changes in the ACC, contributing to pain hypersensitivity. The neurons in layer 3 (L3) of the ACC receive the inputs from the mediodorsal thalamus (MD) and form the feedforward inhibition (FFI) microcircuits. The effects of peripheral nerve injury on the MD-driven FFI in L3 of ACC are unknown. In our study, we record the enhanced excitatory synaptic transmissions from the MD to L3 of the ACC in mice with common peroneal nerve ligation, affecting FFI. Chemogenetically activating the MD-to-ACC projections induces pain sensitivity and place aversion in naive mice. Furthermore, chemogenetically inactivating MD-to-ACC projections decreases pain sensitivity and promotes place preference in nerve-injured mice. Our results indicate that the peripheral nerve injury changes the MD-to-ACC projections, contributing to pain hypersensitivity and aversion., (© 2024. The Author(s).)

This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p < 0.001), mean area under the curve of 0.74 (p < 0.001), mean specificity of 0.82, and mean sensitivity of 0.70 in 10-fold cross-validation. The predictive voxels were mainly within the FPN. The rsFC between the sgACC and FPN is a valuable predictor of antidepressant response in MDD patients. These findings enhance our understanding of the neurobiological mechanisms underlying treatment response and could help inform personalized treatment strategies for MDD., (© 2024. The Author(s).)

Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms are poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated in ASD, but whether GRIN2B mutations lead to sensory abnormalities remains unclear. Here, we report that Grin2b-mutant mice show behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). Grin2b-mutant mice with a patient-derived C456Y mutation (Grin2b C456Y/+ ) show sensory hypersensitivity to mechanical, thermal, and electrical stimuli through supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions. ACC pyramidal neurons show increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity. These results suggest that GluN2B critically regulates ASD-related cortical connectivity and sensory brain functions., (© 2024. The Author(s).)

Background: The incidence of behavioral addictions (BAs) associated with scientific and technological advances has been increasing steadily. Unfortunately, a large number of studies on the structural and functional abnormalities have shown poor reproducibility, and it remains unclear whether different addictive behaviors share common underlying abnormalities. Therefore, our objective was to conduct a quantitative meta-analysis of different behavioral addictions to provide evidence-based evidence of common structural and functional changes., Methods: We conducted systematic searches in PubMed, Web of Science and Scopus from January 2010 to December 2023, supplementing reference lists of high-quality relevant meta-analyses and reviews, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Using anisotropic seed-based D-Mapping (AES-SDM) meta-analysis methods, we compared brain abnormalities between BAs and healthy controls (HCs)., Results: There were 11 GMV studies (287 BAs and 292 HCs) and 26 fMRI studies (577 BAs and 545 HCs) that met inclusion criteria. Compared with HCs, BAs demonstrated significant reductions in gray matter volume (GMV) in (1) right anterior cingulate gyri extending into the adjacent superior frontal gyrus, as well as in the left inferior frontal gyrus and right striatum. (2) the bilateral precuneus, right supramarginal gyrus, and right fusiform gyrus were hyperfunction; (3) the left medial cingulate gyrus extended to the superior frontal gyrus, the left inferior frontal gyrus, and right middle temporal gyrus had hypofunction., Conclusions: Our study identified structural and functional impairments in brain regions involved in executive control, cognitive function, visual memory, and reward-driven behavior in BAs. Notably, fronto-cingulate regions may serve as common biomarkers of BAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Accumulative evidence suggested that the oxytocin system plays a role in socio-emotional disorders, although its role in neuroinflammation-induced anxiety remains unclear., Method: In the present study, anxiety-like behavior was induced in cohorts of animals through repeated lipopolysaccharide (LPS, 0.5 mg/kg, daily, Escherichia coli O55:B5) i.p. injections for seven consecutive days. These different cohorts were subsequently used for anxiety-like behavior assessment with open field test, elevated plus maze, and novelty-suppressed feeding test or for electrophysiology (EEG) recordings of miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs), or local field potential (LFP) in vivo or ex vivo settings. Samples of the anterior cingulate cortex (ACC) from some cohorts were harvested to conduct immunostaining or western blotting analysis of oxytocin, oxytocin receptor, CamkII, GABA, vGAT, vGLUT2, and c-fos. The dendritic spine density was assessed by Golgi-Cox staining., Results: Repeated LPS injections induced anxiety-like behavior with concurrent decreases of oxytocin, vGLUT2, mEPSC, dendritic spine, c-fos, membrane excitability, and EEG beta and gamma oscillations, but increased oxytocin receptor and vGAT expressions in the ACC; all these changes were ameliorated by oxytocin intranasal or local brain (via cannula) administration., Conclusion: Taken together, our data suggested that oxytocin system may be a therapeutic target for developing treatment to tackle neuroinflammation-induced anxiety., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic pain and depression share common neural mechanisms, but their impacts on empathy are different. It is unclear how comorbid depressive symptoms affect empathy-related brain function in patients with chronic pain., Methods: A total of 29 healthy participants and 107 patients with chronic back pain (CBP) were included in this study. All subjects underwent a functional MRI scan with concurrent empathic stimulation. Multiple linear regression, moderation analysis, and mediation analysis were used to explore the impacts of chronic pain and comorbid depression on empathy., Results: The interaction between the pain intensity and the depressive symptoms affected the functional connectivity (FC) of the insula-middle frontal gyrus (MFG), and the severity of the self-rating depression scale (SDS) scores moderated the effect of the pain on the left insula-left MFG FC. Within the CBP group, the emotional contagion (EC) scores served as a mediator in the association between the SDS scores and the FC of the left middle cingulate cortex (MCC)-inferior temporal gyrus (ITG), and the level of cognitive empathy (CE) moderated the effect of the SDS scores on the left MCC-ITG FC., Limitations: There is a lack of research on the effects of depressive symptoms on empathy in individuals with different types of chronic pain., Conclusion: Depressive symptoms were strongly associated with the emotional contagion in patients with chronic back pain. Furthermore, the emotional contagion and the cognitive empathy regulated the effect of the comorbid depressive symptoms on the MCC-ITG connectivity in patients with chronic back pain., Competing Interests: Declaration of competing interest None of the authors has potential conflicts of interest to be disclosed., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Prediction error (PE) is key to perception in the predictive coding framework. However, previous studies indicated the varied neural activities evoked by PE in tinnitus patients. Here, we aimed to reconcile the conflict by (1) a more nuanced view of PE, which could be driven by changing stimulus (stimulus-driven PE [sPE]) and violation of current context (context-driven PE [cPE]) and (2) investigating the aberrant connectivity networks that are engaged in the processing of the two types of PEs in tinnitus patients. Methods: Ten tinnitus patients with normal hearing and healthy controls were recruited, and a local-global auditory oddball paradigm was applied to measure the electroencephalographic difference between the two groups during sPE and cPE conditions. Results: Overall, the sPE condition engaged bottom-up and top-down connections, whereas the cPE condition engaged mostly top-down connections. The tinnitus group showed decreased sensitivity to the sPE and increased sensitivity to the cPE condition. Particularly, the auditory cortex and posterior cingulate cortex were the hubs for processing cPE in the control and tinnitus groups, respectively, showing the orientation to an internal state in tinnitus. Furthermore, tinnitus patients showed stronger connectivity to the parahippocampus and pregenual anterior cingulate cortex for the establishment of the prediction during the cPE condition. Conclusion: These results begin to dissect the role of changes in stimulus characteristics versus changes in the context of processing the same stimulus in mechanisms of tinnitus generation. Impact Statement This study delves into the number dynamics of prediction error (PE) in tinnitus, proposing a dual framework distinguishing between stimulus-driven PE (sPE) and context-driven PE (cPE). Electroencephalographic data from tinnitus patients and controls revealed distinct connectivity patterns during sPE and cPE conditions. Tinnitus patients exhibited reduced sensitivity to sPE and increased sensitivity to cPE. The auditory cortex and posterior cingulate cortex emerged as pivotal regions for cPE processing in controls and tinnitus patients, indicative of an internal state orientation in tinnitus. Enhanced connectivity to the parahippocampus and pregenual anterior cingulate cortex underscores the role of context in tinnitus pathophysiology.

Background: Cerebral mitochondrial and hemodynamic abnormalities have been implicated in Bipolar Disorder pathophysiology, likely contributing to neurometabolic vulnerability-leading to worsen clinical outcomes and mood instability. To investigate neurometabolic vulnerability in patients with BD, we combined multi-modal quantitative MRI assessment of cerebral oxygenation with acute administration of Methylene Blue, a neurometabolic/hemodynamic modulator acting on cerebral mitochondria., Methods: Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo. MRI-based measures of Cerebral Blood Flow and Oxygen Extraction Fraction were integrated to compute Cerebral Metabolic Rate of Oxygen in Frontal Lobe, Anterior Cingulate, and Hippocampus-implicated in BD neurometabolic pathophysiology. Inter-daily variation in mood rating was used to assess mood instability., Results: A decrease in global CBF and CMRO 2 was observed after acutely administrating MB to all participants. Greater regional CMRO 2 reductions were observed after MB, in patients compared to controls in FL (mean = -14.2 ± 19.5 % versus 2.3 ± 14.8 %), ACC (mean = -14.8 ± 23.7 % versus 2.4 ± 15.7 %). The effects on CMRO 2 in those regions were primarily driven by patients with longer disease duration and higher mood instability., Limitations: Sample size; medications potentially impacting on response to MB., Conclusions: An altered neurometabolic response to MB, a mitochondrial/hemodynamic modulator, was observed in patients, supporting the hypothesis of vulnerability to neurometabolic stress in BD. Integrating quantitative imaging of cerebral oxygen metabolism with a mitochondrial-targeting pharmacological challenge could provide a novel biomarker of neurometabolic and cerebrovascular pathophysiology in BD., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABA ACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABA ACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABA ACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABA ACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABA ACC neurons., (© 2024. The Author(s).)

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K + and also the leak K + conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases., Competing Interests: WP, PW, CT, HZ, KC, HS, YT, AL, ZZ, YY, KW, CC, YW, TC No competing interests declared, (© 2024, Peng, Wang, Tan et al.)

Alcohol use disorder is highly prevalent worldwide, with characteristically severe pain sensitivity during withdrawal. Here, we established a mouse model of hyperalgesia during ethanol withdrawal (EW) before addiction to investigate the window for onset and underlying mechanisms. Viral tracing with in vivo microendoscopic and two-photon calcium imaging identified a circuit pathway from dorsal hippocampal CA1 glutamatergic neurons (dCA1 Glu ) to anterior cingulate cortex glutamatergic neurons (ACC Glu ) activated in EW mice with hyperalgesia. Chemogenetic inhibition of this pathway can alleviate hyperalgesia in EW mice, whereas artificial activation recapitulates EW-induced hyperalgesia in naïve mice. These findings demonstrate that the dCA1 Glu → ACC Glu neuronal pathway participates in driving EW-induced hyperalgesia before ethanol dependence in mice.

Introduction: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity (NERS) and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC.) during smoking abstinence predicts NERS and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict NERS and smoking progression., Aims and Methods: Young light smokers (N = 64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 and 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14 hours of nicotine deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on 1 day and a regular cigarette on another day., Results: The probabilistic-reward-task assessed greater NERS was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater NERS., Conclusions: These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression., Clinical Trial Registration: NCT02129387 (preregistered hypothesis: www.clinicaltrials.gov)., Implications: Weaker rsFC within the salience network predicted greater NERS and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The functional neuropeptide S receptor 1 (NPSR1) gene A/T variant (rs324981) is associated with fear processing. We investigated the impact of NPSR1 genotype on fear processing and on symptom reduction following treatment in individuals with spider phobia. A replication approach was applied [discovery sample: Münster (MS) nMS = 104; replication sample Würzburg (WZ) nWZ = 81]. Participants were genotyped for NPSR1 rs324981 [T-allele carriers (risk) versus AA homozygotes (no-risk)]. A sustained and phasic fear paradigm was applied during functional magnetic resonance imaging. A one-session virtual reality exposure treatment was conducted. Change of symptom severity from pre to post treatment and within session fear reduction were assessed. T-allele carriers in the discovery sample displayed lower anterior cingulate cortex (ACC) activation compared to AA homozygotes independent of condition. For sustained fear, this effect was replicated within a small cluster and medium effect size. No association with symptom reduction was found. Within-session fear reduction was negatively associated with ACC activation in T-allele carriers in the discovery sample. NPSR1 rs324981 genotype might be associated with fear processing in the ACC in spider phobia. Interpretation as potential risk-increasing function of the NPSR1 rs324981 T-allele via impaired top-down control of limbic structures remains speculative. Potential association with symptom reduction warrants further research., (© The Author(s) 2024. Published by Oxford University Press.)

Anorexia nervosa (AN) is associated with food restriction and significantly low body weight, but the neurobiology of food avoidance in AN is unknown. Animal research suggests that food avoidance can be triggered by conditioned fear that engages the anterior cingulate and nucleus accumbens. We hypothesized that the neural activation during food avoidance in AN could be modeled based on aversive goal value processing. Nineteen females with AN and thirty healthy controls matched for age underwent functional magnetic resonance brain imaging while conducting a food avoidance task. During active control free-bid and computer-generated forced-bid trials, participants bid money to avoid eating food items. Brain activation was parametrically modulated with the trial-by-trial placed bids. During free-bid trials, the AN group engaged the caudate nucleus, nucleus accumbens, ventral anterior cingulate, and inferior and medial orbitofrontal cortex more than the control group. High- versus low-bid trials in the AN group were associated with higher caudate nucleus response. Emotion dysregulation and intolerance of uncertainty scores were inversely associated with nucleus accumbens free-bid trial brain response in AN. This study supports the idea that food avoidance behavior in AN involves aversive goal value computation in the nucleus accumbens, caudate nucleus, anterior cingulate, and orbitofrontal cortex.

Background: While self-construal and posttraumatic stress disorder (PTSD) are independently associated with altered self-referential processes and underlying default mode network (DMN) functioning, no study has examined how self-construal affects DMN connectivity in PTSD., Methods: A final sample of 93 refugee participants (48 with DSM-5 PTSD or sub-syndromal PTSD and 45 matched trauma-exposed controls) completed a 5-minute resting state fMRI scan to enable the observation of connectivity in the DMN and other core networks. A self-construal index was calculated by substracting scores on the collectivistic and individualistic sub-scales of the Self Construal Scale., Results: Independent components analysis identified 9 active networks-of-interest, and functional network connectivity was determined. A significant interaction effect between PTSD and self-construal index was observed in the anterior ventromedial DMN, with spatial maps localizing this to the left ventromedial prefrontal cortex (vmPFC), extending to the ventral anterior cingulate cortex. This effect revealed that connectivity in the vMPFC showed greater reductions in those with PTSD with higher levels of collectivistic self-construal., Limitations: This is an observational study and causality cannot be assumed. The specialized sample of refugees means that the findings may not generalize to other trauma-exposed populations., Conclusions: Such a finding indicates that self-construal may shape the core neural architecture of PTSD, given that functional disruptions to the vmPFC underpin the core mechanisms of extinction learning, emotion dysregulation and self-referential processing in PTSD. Results have important implications for understanding the universality of neural disturbances in PTSD, and suggest that self-construal could be an important consideration in the assessment and treatment of post-traumatic stress reactions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors. However, the extent to which these disorders share common underlying neuropathological mechanisms remains unclear. To investigate the similarities and differences in task-evoked brain activation patterns between patients with PTSD and MDD., Methods: A coordinate-based meta-analysis was conducted across 35 PTSD studies (564 patients and 543 healthy controls) and 125 MDD studies (4049 patients and 4170 healthy controls) using anisotropic effect-size signed differential mapping software., Results: Both PTSD and MDD patients exhibited increased neural activation in the bilateral inferior frontal gyrus. However, PTSD patients showed increased neural activation in the right insula, left supplementary motor area extending to median cingulate gyrus and superior frontal gyrus (SFG), and left fusiform gyrus, and decreased neural activation in the right posterior cingulate gyrus, right middle temporal gyrus, right paracentral lobule, and right inferior parietal gyrus relative to MDD patients., Conclusion: Our meta-analysis suggests that PTSD and MDD share some similar patterns of brain activation, but also have distinct neural signatures. These findings contribute to our understanding of the potential neuropathology underlying these disorders and may inform the development of more targeted and effective treatment and intervention strategies. Moreover, these results may provide useful neuroimaging targets for the differential diagnosis of MDD and PTSD., Competing Interests: Declaration of competing interest OJR held a Medical Research Council Proximity-to-Discovery award with Roche and an investigator-initiated trial with medication donated by Lundbeck, he has completed consultancy work for Peak, Ieso Digital Health, Roche and Blackthorn therapeutics, and sat on the committee of the British Association of Psychopharmacology until 2022. Other authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Gambling activity evolves along a continuum from recreational to Gambling Disorder (GD) and a particular challenge is to identify whether there are some neurophysiological particularities already present in gamblers at an early stage. Our main goal was to determine whether, in the gamblers' population, neural responses generated during uncertain decisions were different depending on problematic gambling risk defined by the Canadian Problem Gambling Index (CPGI). We tested the following hypothesis, that the Problem Gambling group would show a different brain activity related to outcomes processing than people with low risk., Methods: For this purpose, we established a relatively homogeneous population of Online Poker Players divided into two groups according to the CPGI (Low Risk and Problem Gambling). By means of high-density EEG, we compared the spatio-temporal dynamics generated during the completion of the Iowa Gambling Task., Results: One specific topographic map was observed between 150-175 ms after a negative outcome for both groups, whereas it was displayed in the win condition only for the Problem Gambling group. We found that the Global Field Power of this map was negatively correlated with participants' adherence to a strategy. Source localization identified Anterior Cingulate Cortex and Temporal regions as generators of this map., Discussion and Conclusions: Reward hypersensitivity EEG responses identified in the early outcome process could constitute a potential biomarker of problematic gambling.

Real-time fMRI neurofeedback (rtfMRI-NF) has emerged as a promising intervention for psychiatric disorders, yet its clinical efficacy remains underexplored due to an incomplete mechanistic understanding. This study aimed to delineate the whole-brain mechanisms underpinning the effects of rtfMRI-NF on repetitive negative thinking in depression. In a double-blind randomized controlled trial, forty-three depressed individuals underwent NF training targeting the functional connectivity (FC) between the posterior cingulate cortex and the right temporoparietal junction, linked to rumination severity. Participants were randomly assigned to active or sham groups, with the sham group receiving synthesized feedback mimicking real NF signal patterns. The active group demonstrated a significant reduction in brooding rumination scores (d = -1.52, p < 0.001), whereas the sham group did not (d = -0.23, p = 0.503). While the target FC did not show discernible training effects or group differences, connectome-based predictive modeling (CPM) analysis revealed that the interaction between brain activity during regulation and brain response to the feedback signal was the critical factor in explaining treatment outcomes. The model incorporating this interaction successfully predicted rumination changes across both groups. The FCs significantly contributing to the prediction were distributed across brain regions, notably the frontal control, salience network, and subcortical reward processing areas. These results underscore the importance of considering the interplay between brain regulation activities and brain response to the feedback signal in understanding the therapeutic mechanisms of rtfMRI-NF. The study affirms rtfMRI-NF's potential as a therapeutic intervention for repetitive negative thinking and highlights the need for a nuanced understanding of the whole-brain mechanisms contributing to its efficacy., (© 2024. The Author(s).)

Background: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy., Methods: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method., Results: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen's d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen's d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen's d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS., Conclusion: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults., Competing Interests: Declaration of Competing interest All authors report no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear., Method: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels., Results: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction., Conclusion: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Brain imaging suggests the involvement of the limbic system, particularly the cingulate gyrus (GC), in dogs with idiopathic epilepsy (IE)., Hypothesis: A correlation exists between the side of interictal epileptiform discharges (IEDs) and the volume of the ipsilateral GC (GCe) in dogs with IE., Animals: Dogs admitted to the neurological consultation (32 with epileptic seizures and 13 control) were included., Methods: This retrospective, blinded study followed the International Veterinary Epilepsy Task Force recommendations for diagnosing IE at the Tier III confidence level. The IE group included 18 and 14 dogs with IEDs in the left and right hemispheres, respectively (median age: 36 months, median weight: 19.5 kg), whereas the control group included 13 dogs (median age: 32 months, median weight: 20 kg). Whole-brain and GC-volumetric assessments were performed by a semiautomated method., Results: In the control group, the volume of the GC was: left, from 743.63 to 1001.61 mm 3 , right, from 789.35 to 1015.86 mm 3 . In the study group, the volume of the GC was: left, from 720.88 to 1054.9 mm 3 and right, from 566.29 to 987.77 mm 3 . In dogs with IE, GCe volume was significantly lower than the mean volume of the GC in the control group relative to total intracranial volume (TIV; P = .00044)., Conclusions and Clinical Importance: Alterations in the volume of the GC provide insights into structural changes during IE. The use of semiautomatic volumetry provides an advantage by reducing the potential for human error., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Interoception, the sense of the physiological condition of our body, is impaired in individuals with autism spectrum disorders. Evidence suggests that subclinical autistic traits are mild manifestations of autistic symptoms, present in the general population. We examined the resting-state functional connectivity (rsFC) associating with interoception and autistic traits in 62 healthy young adults. Autistic traits correlated negatively with the rsFC between the lateral ventral anterior insula and anterior cingulate cortex. Interoceptive accuracy and sensibility correlated positively with the rsFC between interoceptive brain networks and the cerebellum, supplementary motor area, and visual regions. The results suggest that a negative relationship between interoception and autistic traits is largely accounted for by both self-report measures and decreased rsFC amongst the interoceptive brain network., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Bipolar disorder (BD) is chronic and disabling, with depression accounting for the majority of time with illness. Recent research demonstrated a transformative advance in the clinical efficacy of transcranial magnetic stimulation for treatment-resistant major depressive disorder (MDD) using an accelerated schedule of intermittent theta-burst stimulation (aiTBS), but the effectiveness of this treatment for treatment-refractory BD is unknown., Objective: To evaluate the effectiveness of aiTBS for treatment-refractory BD., Design, Setting, and Participants: This randomized clinical trial, conducted from March 2022 to February 2024, included individuals with treatment-resistant BD with moderate to severe depressive episodes referred from the Penn Bipolar outpatient clinic. Included patients had 2 or more prior failed antidepressant trials by Antidepressant Treatment History Form criteria and no other primary psychiatric diagnosis, were receiving a mood stabilizer for 4 or more weeks, and had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher., Intervention: Prior to treatment, resting-state functional magnetic resonance imaging was used to compute personalized left dorsolateral prefrontal cortex target by connectivity to subgenual anterior cingulate cortex. Patients were randomized 1:1 to 10 sessions per day of imaging-guided active or sham aiTBS for 5 days with 1 session per hour at 90% resting motor threshold for 90 000 pulses total., Main Outcome and Measures: The main outcome was repeated MADRS scores before and after treatment., Results: A total of 24 participants (12 [50%] female; 12 [50%] male; mean [SD] age, 43.3 [16.9] years) were randomized to active (n = 12) or sham (n = 12) aiTBS. All participants completed treatment and 1-month follow-up. MADRS scores were significantly lower in the active group (mean [SD], 30.4 [4.8] at baseline; 10.5 [6.7] after treatment) than in the sham group (28.0 [5.4] at baseline; 25.3 [6.7] after treatment) at treatment end (estimated difference, -14.75; 95% CI, -19.73 to -9.77; P < .001; Cohen d, -2.19)., Conclusion and Relevance: In this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD. Further trials are needed to determine aiTBS durability and to compare with other treatments., Trial Registration: ClinicalTrials.gov Identifier: NCT05228457.

Background: Benign childhood epilepsy with centrotemporal spikes (BECTS), a common pediatric epilepsy, may lead to cognitive decline when compounded by Electrical Status Epilepticus during Sleep (ESES). Emerging evidence suggests that disruptions in the Salience Network (SN) contribute significantly to the cognitive deficits observed in BECTS-ESES. Our study rigorously investigates the dynamic functional connectivity (dFC) within the SN and its correlation with cognitive impairments in BECTS-ESES, employing advanced neuroimaging and neuropsychological assessments., Methods: In this research, 45 patients diagnosed with BECTS-ESES and 55 age-matched healthy controls (HCs) participated. We utilized resting-state functional magnetic resonance imaging (fMRI) and Independent Component Analysis (ICA) to identify three fundamental SN nodes: the right Anterior Insula (rAI), left Anterior Insula (lAI), and the Anterior Cingulate Cortex (ACC). A two-sample t-test facilitated the comparison of dFC between these pivotal regions and other brain areas., Results: Significantly, the BECTS-ESES group demonstrated increased dFC, particularly between the ACC and the right Middle Occipital Gyrus, and from the rAI to the right Superior Parietal Gyrus and Cerebellum, and from the lAI to the left Postcentral Gyrus. Such dFC augmentations provide neural insights potentially explaining the neuropsychological deficits in BECTS-ESES children. Employing comprehensive neuropsychological evaluations, we mapped these dFC disruptions to specific cognitive impairments encompassing memory, executive functioning, language, and attention. Through multiple regression analysis and path analysis, a preliminary but compelling association was discovered linking dFC disturbances directly to cognitive impairments. These findings underscore the critical role of SN disruptions in BECTS-ESES cognitive dysfunctions., Limitation: Our cross-sectional design and analytic methods preclude definitive mediation models and causal inferences, leaving the precise nature of dFC's mediating role and its direct impact by BECTS-ESES partially unresolved. Future longitudinal and confirmatory studies are needed to comprehensively delineate these associations., Conclusion: Our study heralds dFC within the SN as a vital biomarker for cognitive impairment in pediatric epilepsy, advocating for targeted cognitive-specific interventions in managing BECTS-ESES. The preliminary nature of our findings invites further studies to substantiate these associations, offering profound implications for the prognosis and therapeutic strategies in BECTS-ESES, thereby underlining the importance of this research in the field of pediatric neurology and epilepsy management., Competing Interests: Declaration of competing interest The authors declare that they have no computing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Childhood neglect is associated with brain changes, yet the molecular mechanisms and behavioral relevance underlying such associations remain elusive., Methods: We calculated fractional amplitude of low-frequency fluctuations (fALFF) using resting-state functional MRI and tested their correlation with childhood neglect across a large sample of 510 healthy young adults. Then, we investigated the spatial relationships of the identified neural correlates of childhood neglect with gene expression, neurotransmitter, and behavioral domain atlases., Results: We found that more severe childhood neglect was correlated with higher fALFF in the bilateral anterior cingulate cortex. Remarkably, the identified neural correlates of childhood neglect were spatially correlated with expression of gene categories primarily involving neuron, synapse, ion channel, cognitive and perceptual processes, and physiological response and regulation. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including serotonin and GABA. Finally, neural correlates of childhood neglect were associated with diverse behavioral domains implicating mental disorders, emotion, cognition, and sensory perception., Limitations: The cross-sectional study design cannot unequivocally establish causality., Conclusions: Our findings may not only add to the current knowledge regarding the relationship between childhood neglect and mental health, but also have clinical implications for developing preventive strategies for individuals exposed to childhood neglect who are at risk for mental disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest Authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Depression is linked to cognitive biases towards more negative and less positive self-relevant information. Rumination, perseverative negative thinking about the past and the self, may contribute to these biases., Methods: 159 adolescents (12-18 years), with a range of depression symptoms, completed the SRET during fMRI. Multiple regressions tested associations between conventional self-report and ecological momentary assessment (EMA) measured rumination, and neural and behavioral responses during a self-referent encoding task (SRET)., Results: Higher rumination (conventional self-report and EMA) was associated with more negative and fewer positive words endorsed and recalled. Higher self-reported (but not EMA) rumination was associated with higher accuracy in recognizing negative words and greater insula and dorsal anterior cingulate activity to negative versus positive words., Limitations: The sample included mostly non-Hispanic White participants with household incomes above the national average, highlighting the need for replication in more diverse samples. Word endorsement discrepancies required fMRI analyses to model neural response to viewing negative versus positive words., Conclusions: Adolescents with higher rumination endorsed and recalled more negative and fewer positive words and recognized more negative words during the SRET. Higher insula reactivity, a key region for modulating externally-oriented attention and internally-oriented self-referential processes, may contribute to links between rumination and negative memory biases. These findings provide insight into neurocognitive mechanisms underlying depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes., Methods: 195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-)., Results: MDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp 2  = 0.02), dorsolateral prefrontal cortex (ηp 2  = 0.01) and dorsal anterior/mid cingulate cortex (ηp 2  = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD., Limitations: Limitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants., Conclusions: AnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group., Competing Interests: Declaration of competing interest This work has been supported in part by The William K. Warren Foundation and the National Institute of General Medical Sciences center grant award number P20GM121312. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Maria Ironside, Rayus Kuplicki, Jennifer Stewart, Robin Aupperle, and Martin Paulus receive funding from the National Institute of General Medical Sciences (NIGMS) center grant P20GM121312; Maria Ironside has additional funding from National Institute of Mental Health (NIMH; R01MH132565). Sahib Khalsa has grant funding from the NIMH (K23MH112949, R01MH127225); Robin Aupperle has additional grant funding from NIMH (K23MH108707; R01MH123691); Jennifer Stewart has additional grant funding from the National Institute of Drug Abuse (NIDA) (R01DA050677), Rayus Kuplicki has additional funding from NIDA (R01DA050677); and Martin Paulus has additional grant funding from the NIDA (U01DA041089, R01DA050677)., (Copyright © 2024. Published by Elsevier B.V.)

Background/Objectives : Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms. Methods : We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements. Results : The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores ( p 's = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p 's < 0.010). Conclusions : The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample., Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging., Results: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05)., Limitations: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression)., Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity., Competing Interests: Declaration of competing interest Dr. Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. Dr. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or conflicts of interest. All authors have approved the final article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Research indicates that hearing loss significantly contributes to tinnitus, but it alone does not fully explain its occurrence, as many people with hearing loss do not experience tinnitus. To identify a secondary factor for tinnitus generation, we examined a unique dataset of individuals with intermittent chronic tinnitus, who experience fluctuating periods of tinnitus. EEGs of healthy controls were compared to EEGs of participants who reported perceiving tinnitus on certain days, but no tinnitus on other days.. The EEG data revealed that tinnitus onset is associated with increased theta activity in the pregenual anterior cingulate cortex and decreased theta functional connectivity between the pregenual anterior cingulate cortex and the auditory cortex. Additionally, there is increased alpha effective connectivity from the dorsal anterior cingulate cortex to the pregenual anterior cingulate cortex. When tinnitus is not perceived, differences from healthy controls include increased alpha activity in the pregenual anterior cingulate cortex and heightened alpha connectivity between the pregenual anterior cingulate cortex and auditory cortex. This suggests that tinnitus is triggered by a switch involving increased theta activity in the pregenual anterior cingulate cortex and decreased theta connectivity between the pregenual anterior cingulate cortex and auditory cortex, leading to increased theta-gamma cross-frequency coupling, which correlates with tinnitus loudness. Increased alpha activity in the dorsal anterior cingulate cortex correlates with distress. Conversely, increased alpha activity in the pregenual anterior cingulate cortex can transiently suppress the phantom sound by enhancing theta connectivity to the auditory cortex. This mechanism parallels chronic neuropathic pain and suggests potential treatments for tinnitus by promoting alpha activity in the pregenual anterior cingulate cortex and reducing alpha activity in the dorsal anterior cingulate cortex through pharmacological or neuromodulatory approaches., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose concerning the research paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex., Materials and Methods: Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season. Participants underwent MRI and a cognitive battery (ImPACT) before and shortly after the football season. A control group of noncontact/limited-contact-sport athletes was formed from 2 cohorts: one from the same school and protocol and another from a separate, nearly identical study., Results: Sixty-three football players and 34 control athletes were included in the cognitive performance analysis. Preseason, the control group scored significantly higher on the ImPACT Visual Motor ( P = .04) and Reaction Time composites ( P = .006). These differences increased postseason ( P = .003, P < .001, respectively). Additionally, the control group had significantly higher postseason scores on the Visual Memory composite ( P = .001). Compared with controls, football players showed significantly less improvement in the Verbal ( P = .04) and Visual Memory composites ( P = .01). A significantly greater percentage of contact athletes had lower-than-expected scores on the Verbal Memory (27% versus 6%), Visual Motor (21% versus 3%), and Reaction Time composites (24% versus 6%). Among football players, a higher RWEcp was significantly associated with greater increments in ImPACT Reaction Time ( P = .03) and Total Symptom Scores postseason ( P = .006). Fifty-seven football players and 13 control athletes were included in the imaging analyses. Postseason, football players showed significant decreases in interhemispheric connectivity of the dorsal anterior cingulate cortex ( P = .026) and within-network connectivity of the salience network ( P = .018). These decreases in dorsal anterior cingulate cortex interhemispheric connectivity and within-network connectivity of the salience network were significantly correlated with deteriorating ImPACT Total Symptom ( P = .03) and Verbal Memory scores ( P = .04)., Conclusions: Head impact exposure during a single season of high school football is negatively associated with cognitive performance and brain network connectivity. Future studies should further characterize these short-term effects and examine their relationship with long-term sequelae., (© 2024 by American Journal of Neuroradiology.)

The purpose of this study was to assess the functional connectivity of the posterior cingulate cortex in autism spectrum disorder (ASD). We used resting-state functional magnetic resonance imaging (rsfMRI) brain scans of adolescents diagnosed with ASD and a neurotypical control group. The Autism Brain Imaging Data Exchange (ABIDE) consortium was utilized to acquire data from the University of Michigan (145 subjects) and data from the New York University (183 subjects). The posterior cingulate cortex showed reduced connectivity with the anterior cingulate cortex for the ASD group compared to the control group. These two brain regions have previously both been linked to ASD symptomology. Specifically, the posterior cingulate cortex has been associated with behavioral control and executive functions, which appear to be responsible for the repetitive and restricted behaviors (RRB) in ASD. Our findings support previous data indicating a neurobiological basis of the disorder, and the specific functional connectivity changes involving the posterior cingulate cortex and anterior cingulate cortex may be a potential neurobiological biomarker for the observed RRBs in ASD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Both ruminative thought processes and adverse childhood experiences (ACEs) are well-established risk factors for the emergence and maintenance of depression. However, the neurobiological mechanisms underlying these associations remain poorly understood., Methods: We examined resting-state functional magnetic resonance imaging data (3 T Tim Trio MR scanner; Siemens, Erlangen) of 44 individuals diagnosed with an acute depressive episode. Specifically, we focused on investigating functional brain activity and connectivity within and between three large-scale neural networks associated with processes affected in depression: the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Correlational and regression-based analyses were performed., Results: Our regions of interest analyses revealed that region-specific spontaneous neural activity in the anterior DMN was associated with self-reported trait rumination, specifically, the pregenual anterior cingulate cortex (pgACC). Furthermore, using a liberal statistical threshold, we found that spontaneous neural activity of the ventromedial prefrontal cortex and the pgACC were associated with depression symptom severity. Neither spontaneous neural activity in the SN and CEN nor functional connectivity within and across the investigated networks was associated with depression severity or rumination. Furthermore, there was no association between ACEs and brain activity and connectivity., Limitations: Lack of a formal control group or low-risk group for comparison., Conclusions: Overall, our results indicate network-specific changes in spontaneous brain activity, that are linked to both depression severity and rumination. Findings underscore the crucial role of the pgACC in depression and contribute to a dimensional and symptom-based understanding of depression-related network imbalances., Competing Interests: Declaration of competing interest Simone Grimm has served as a consultant to and received research support from Boehringer Ingelheim Pharma. Malek Bajbouj has served as a consultant to GH Research, Janssen, Bayer, and Boehringer Ingelheim., (Copyright © 2024. Published by Elsevier B.V.)

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)