SEARCH · Search PubMed

Results for “anterior cingulate cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

8 recordsLinked to original sources

PubMed2026

Altered neural electrophysiological properties in the anterior cingulate cortex in a mouse model of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disease associated with multiple metabolic and behavioural abnormalities converging into a distinctive clinical phenotype characterized by insatiable appetite leading to hyperphagia and eventual morbid obesity. The PWS spectrum results from deficiencies in paternally imprinted chromosome 15q11-13 region clustering around non-coding RNA multiple-repeat gene Snord116. A PWS mouse model with paternal Snord116 deletion (Snord116del) revealed multiple expected behavioural traits but failed to reproduce obesity in experimental paradigms designed to uncover homeostatic hypothalamic mechanisms of hyperphagia, while the possibility for pathologic hedonic overdrive underlying hyperphagic behaviours was not studied. In Snord116del mice, we examined functional properties of pyramidal neurons (PyNs) in the anterior cingulate cortex (ACC), the brain area commonly associated with goal-oriented and choice-outcome processing, including the value assessment of food items. We found indications of higher dendritic complexity and stronger afferent excitatory connectivity compared to controls. A strong excitatory input into Snord116del PyNs was balanced by a more hyperpolarized resting membrane potential, rendering lower soma excitability, improved signal-to-noise discrimination and stronger low-pass filtering. The enhanced excitatory network-tuning ability originating from Snord116 deficiency may explain the previously reported better performance of Snord116del over wild-type mice in working-for-food behavioural tests, whereas in humans it might entail exaggerated reward-seeking behaviour since early childhood when food is the main attractant. Our analysis of previously published genomic databases revealed candidate genes responsible for the abnormal functional neuronal phenotype caused by Snord116 deletion, including K+ and Na+ voltage-dependent ion channels, protein kinases, phosphatases and components of the mechanistic target of rapamycin (mTOR) intracellular signalling pathway. KEY POINTS: Altered biophysical characteristics and parameters of neuronal connectivity in pyramidal neurons in the anterior cingulate cortex (ACC) in Snord116 deletion mice. Alterations include augmented afferent synaptic input, altered resting state and firing properties of ACC pyramidal neurons. Our findings uncover a possible mechanistic basis for altered ACC functionality in Prader-Willi syndrome.

Animals↗

PubMed2026

Shared genetic architecture and neurobiological pathways of problematic alcohol use and anxiety disorders.

Problematic alcohol use (PAU) and anxiety disorders (ANX) frequently co-occur, implying shared genetic and neurobiological foundations. However, the directionality of potential causal relationships and the specific mechanisms underlying the overlap remain unclear. Thus, we investigated the shared genetic architecture and neurobiological pathways between PAU and ANX using a multimethod genomic approach. We analyzed summary statistics from genome-wide association studies (GWAS) of PAU and ANX using Mendelian Randomization to assess causal associations between ANX and PAU. We used MiXeR to assess the overall shared genomic architecture, Local Analysis of (co)Variant Association to estimate regional genetic correlations, and conjunctional false discovery rate (conjFDR) to identify individual overlapping loci. We used FUMA to map single-nucleotide polymorphisms (SNPs) to independent loci, conduct differential gene expression analyses across 30 general and 54 specific tissue types, and perform cell-type specificity analyses using a human brain cell atlas. Druggability of identified targets was also evaluated. Mendelian Randomization analyses indicated bidirectional causal associations between ANX and PAU. MiXeR identified moderate polygenic overlap (52.5%) and genetic correlation (rg = 0.44) between the traits, with high effect direction concordance among shared estimated causal variants (86.4%). ConjFDR identified 97 shared lead SNPs, of which 89 had concordant and 8 discordant effects on PAU and ANX. These loci mapped to 97 genes, including DRD2 and PDE4B, genes linked to dopaminergic and cAMP signaling pathways, respectively. Concordant gene expression was enriched in brain, nerve, adrenal gland, esophagus, stomach, and colon, with enriched expression specifically in the prefrontal cortex, anterior cingulate cortex, hippocampus, hypothalamus, substantia nigra and amygdala. FUMA cell-type enrichment analysis identified associations predominantly in neurons from the cerebral cortex, hippocampus, and thalamus. We found substantial genetic and neurobiological overlap between PAU and ANX, highlighting reciprocal, causal relationships between the traits, with differentially expressed genes enriched in addiction- and anxiety-relevant brain regions. These findings support shared genetic and neurobiological mechanisms linking PAU and ANX, while acknowledging that some signals may reflect broader internalizing or psychiatric liability.

Journal Article↗

PubMed2026

Prenatal Alcohol Exposure Produces Selective Changes in Neuroimmune Gene Expression Across Brain Regions of Adult Mice.

BACKGROUND: An overwhelming body of evidence suggests neuroimmune dysfunction as a key underlying mechanism of fetal alcohol spectrum disorder (FASD)-associated adverse central nervous system (CNS) outcomes. While few studies have highlighted the lingering effects of prenatal alcohol exposure (PAE) on producing specific immune factors, others suggest a primed neuroimmune state in adulthood, in which a proinflammatory bias is unmasked following subsequent immune activation in later life. However, the PAE-induced neuroimmune landscape in adulthood remains poorly defined. We hypothesized that PAE induces long-term changes in gene expression linked to neuroimmune function that may be brain region-specific. METHODS: Using long-read next-generation RNA sequencing of brain tissues from a previously established model of a moderate PAE in mice, we compared across six regions: medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), hypothalamus, hippocampus, midbrain, and medulla. A comprehensive bioinformatics analysis investigated PAE-induced changes, dysregulated gene pathways, and transcriptional regulators with a focus on neuroimmune function. RESULTS: Our data identified at least 60 differentially expressed genes per brain region, many of which were associated with neuroimmune function. Upregulation of multiple pro-inflammatory factors and pathways was observed, suggesting ongoing baseline neuroimmune activation, potentially involving PXR, TNF, TLR4, the complement pathway, and various cytokine and chemokine signaling. A comparative analysis identified multiple upstream transcriptional regulators across multiple brain regions, including MECP2, TCF7L2, and IL-4. Importantly, this unbiased analysis revealed heterogeneity across brain regions in the activation of canonical immune pathways and highlighted previously unprecedented roles of pathways such as PXR, matrix metalloproteases, and cytokine signaling (e.g., IL-15, IL-27, IL-17) in PAE. CONCLUSIONS: PAE creates a unique inflammatory signature in the adult brain, even in the absence of secondary injury, with novel patterns of region-specific changes in genes implicated in glial-immune function. These data identify potential immune targets to elucidate the mechanisms underlying behavioral dysfunction and provide a framework for future therapeutic interventions.

Animals↗

PubMed2026

Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment resistant depression.

Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-naïve participants with TRD (Montgomery-Åsberg Depression Rating Scale ≥20; ≥1 failed antidepressant trial). Participants were randomized to active (n = 12) or sham (n = 12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P < 0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t₂₂ = -3.82; P < 0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F₁₃,₂₂₂ = 4.93; P < 0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n = 12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P = 0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.

Journal Article↗

PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗

PubMed2026

Predicted brain-regional gene expression patterns in individuals living with Alzheimer's disease.

Studying brain gene expression in Alzheimer's Disease (AD) remains difficult as postmortem brain is difficult to access, cannot be used to guide donor treatment, may be confounded by environmental factors before and after death, and is difficult to link to early AD states or disease progression. To circumvent these limitations, several studies have tested blood transcriptome biomarkers for AD. However, gene-expression levels in the blood have limited correlation with those in the brain. To evaluate the potential of monitoring Alzheimer's progression with peripheral data, we used transcriptome-imputation to identify brain-region-specific AD-associated gene-expression differences in cohorts with blood-based transcriptome data. This approach provides a high-resolution image of AD-associated molecular differences in the brains of individuals actively living with disease. We analyzed eight AD studies (777 AD cases, 779 cognitively unimpaired controls), imputing transcriptomes in 10 brain regions via the Brain Gene Expression and Network Imputation Engine (BrainGENIE). Hundreds of differentially expressed genes (DEGs) associated with AD were identified in nine brain regions, with anterior cingulate cortex and amygdala showing the most differential expression. AD-associated genes were enriched in pathways such as proteostasis, mitochondrial dysfunction, and immune activation. We observed significant yet moderate concordance between imputed AD-associated changes and those directly measured in the dorsolateral prefrontal cortex and cerebellum. These transcriptomic changes can guide future in vitro studies focused on pathogenesis or be targets of novel therapeutic development. In conclusion, we demonstrated the scope and utility of brain expression imputation from the peripheral transcriptome, laying the groundwork for biomarker discovery and prospective AD studies.

Alzheimer Disease↗

PubMed2026

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent↗

PubMed2024

Transcriptomic pathology of neocortical microcircuit cell types across psychiatric disorders.

Psychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are characterized by altered cognition and mood, brain functions that depend on information processing by cortical microcircuits. We hypothesized that psychiatric disorders would display cell type-specific transcriptional alterations in neuronal subpopulations that make up cortical microcircuits: excitatory pyramidal (PYR) neurons and vasoactive intestinal peptide- (VIP), somatostatin- (SST), and parvalbumin- (PVALB) expressing inhibitory interneurons. Using laser capture microdissection followed by RNA sequencing (LCM-seq), we performed cell type-specific molecular profiling of subgenual anterior cingulate cortex, a region implicated in mood and cognitive control. We sequenced libraries from 130 whole cells pooled per neuronal subtype (VIP, SST, PVALB, superficial and deep PYR) in 76 subjects from the University of Pittsburgh Brain Tissue Donation Program, evenly split between MDD, BD and SCZ subjects and healthy controls (totaling 380 bulk transcriptomes from ~50,000 neurons). We identified hundreds of differentially expressed (DE) genes and biological pathways across disorders and neuronal subtypes, with the vast majority in interneurons, particularly PVALB. While DE genes were unique to each cell type, there was a partial overlap across disorders for genes involved in the formation and maintenance of neuronal circuits. We observed coordinated alterations in biological pathways between select pairs of microcircuit cell types, also partially shared across disorders. Finally, DE genes coincided with known risk variants from psychiatric genome-wide association studies, suggesting cell type-specific convergence between genetic and transcriptomic risk for psychiatric disorders. Our study suggests transdiagnostic cortical microcircuit pathology in SCZ, BD, and MDD and sets the stage for larger-scale studies investigating how cell circuit-based changes contribute to shared psychiatric risk.

Humans↗