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Communications Biology Jun 2024Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an...
Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.
Topics: Fear; Animals; Benzodiazepines; Hippocampus; Extinction, Psychological; Male; Midline Thalamic Nuclei; Rats; Anti-Anxiety Agents; Mice
PubMed: 38877285
DOI: 10.1038/s42003-024-06417-w -
Translational Psychiatry Jun 2024Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced...
Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced dosage of Cyfip1 is a risk factor for neuropsychiatric disorder, as evidenced by its involvement in the 15q11.2 (BP1-BP2) copy number variant: deletion carriers are haploinsufficient for CYFIP1 and exhibit a two- to four-fold increased risk of schizophrenia, autism and/or intellectual disability. Here, we model the contributions of Cyfip1 to behavioural flexibility and related fronto-striatal neural network function using a recently developed haploinsufficient, heterozygous knockout rat line. Using multi-site local field potential (LFP) recordings during resting state, we show that Cyfip1 heterozygous rats (Cyfip1) harbor disrupted network activity spanning medial prefrontal cortex, hippocampal CA1 and ventral striatum. In particular, Cyfip1 rats showed reduced influence of nucleus accumbens and increased dominance of prefrontal and hippocampal inputs, compared to wildtype controls. Adult Cyfip1 rats were able to learn a single cue-response association, yet unable to learn a conditional discrimination task that engages fronto-striatal interactions during flexible pairing of different levers and cue combinations. Together, these results implicate Cyfip1 in development or maintenance of cortico-limbic-striatal network integrity, further supporting the hypothesis that alterations in this circuitry contribute to behavioural inflexibility observed in neuropsychiatric diseases including schizophrenia and autism.
Topics: Animals; Haploinsufficiency; Rats; Schizophrenia; Male; Adaptor Proteins, Signal Transducing; Prefrontal Cortex; Autistic Disorder; CA1 Region, Hippocampal; Disease Models, Animal; Nerve Net; Behavior, Animal; Corpus Striatum; Ventral Striatum
PubMed: 38876996
DOI: 10.1038/s41398-024-02969-x -
Psychiatry Research. Neuroimaging Jun 2024Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the... (Review)
Review
Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants.
PubMed: 38875766
DOI: 10.1016/j.pscychresns.2024.111842 -
Turkish Neurosurgery Aug 2023Taste consists of perception and sensation. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any...
Taste consists of perception and sensation. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any disruption of this pathway, whether it affects sensation or perception, can result in taste disorders. Stereotactic procedures involving the thalamus may result in gustatory complications. A 41-year-old female patient who underwent stereotactic drainage of a thalamic cyst suffered transient ageusia. Subsequently, she developed metallic taste perception. When her stereotactic plan was re-evaluated, it was noted that the posteromedial ventral thalamus nucleus was in the path of the needle tract and the needle had passed through it. Follow-up was recommended and her symptoms completely resolved within 2 months following surgery. Modern imaging techniques allow for the visualization of neural structures related to the sense of taste. Additionally, care must be taken when planning stereotactic procedures for such lesions.
PubMed: 38874247
DOI: 10.5137/1019-5149.JTN.43601-23.3 -
Brain and Behavior Jun 2024Low self-esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low...
INTRODUCTION
Low self-esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self-esteem show a distinct neural pathophysiology. Previous studies linked low self-esteem to reduced task-induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya-Maldonado et al. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self-esteem.
METHODS
Eighty-three MDD patients performed the desire-reason dilemma task and completed the Rosenberg Self-Esteem Scale (RSES). Brain activity during bottom-up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery-Åsberg Depression Rating Scale. To corroborate the findings, we compared self-esteem scores between patient subgroups with impaired task-induced deactivation (n = 31) and with preserved task-induced deactivation (n = 31) of the pgACC.
RESULTS
Consistent with our a priori hypothesis, activity in a bilateral fronto-striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task-induced pgACC deactivation showed lower self-esteem (t (52.82) = -2.27; p = .027, d = 0.58) compared to those with preserved task-induced pgACC deactivation.
CONCLUSIONS
We conclude that low self-esteem in MDD patients is linked to a task-induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self-esteem.
Topics: Humans; Depressive Disorder, Major; Self Concept; Reward; Male; Female; Adult; Magnetic Resonance Imaging; Gyrus Cinguli; Middle Aged; Ventral Striatum
PubMed: 38873863
DOI: 10.1002/brb3.3545 -
Journal of Abdominal Wall Surgery : JAWS 2024Health disparities are pervasive in surgical care. Particularly racial and socioeconomic inequalities have been demonstrated in emergency general surgery outcomes, but...
Health disparities are pervasive in surgical care. Particularly racial and socioeconomic inequalities have been demonstrated in emergency general surgery outcomes, but less so in elective abdominal wall reconstruction (AWR). The goal of this study was to evaluate the disparities in referrals to a tertiary hernia center. A prospectively maintained hernia database was queried for patients who underwent open ventral hernia (OVHR) or minimally invasive surgical (MISR) repair from 2011 to 2022 with complete insurance and address information. Patients were divided by home address into in-state (IS) and out-of-state (OOS) referrals as well as by operative technique. Demographic data and outcomes were compared. Standard and inferential statistical analyses were performed. Of 554 patients, most were IS (59.0%); 334 underwent OVHR, and 220 underwent MISR. IS patients were more likely to undergo MISR (OVHR: 45.6% vs. 81.5%, laparoscopic: 38.2% vs. 14.1%, robotic: 16.2% vs. 4.4%; < 0.001) when compared to OOS referrals. Of OVHR patients, 44.6% were IS and 55.4% were OOS. Patients' average age and BMI, sex, ASA score, and insurance payer were similar between IS and OOS groups. IS patients were more often Black (White: 77.9% vs. 93.5%, Black: 16.8% vs. 4.3%; < 0.001). IS patients had more smokers (12.1% vs. 3.2%; = 0.001), fewer recurrent hernias (45.0% vs. 69.7%; < 0.001), and smaller defects (155.7 ± 142.2 vs. 256.4 ± 202.9 cm; < 0.001). Wound class, mesh type, and rate of fascial closure were similar, but IS patients underwent fewer panniculectomies (13.4% vs. 34.1%; < 0.001), component separations (26.2% vs. 51.4%; < 0.001), received smaller mesh (744.2 ± 495.6 vs. 975.7 ± 442.3 cm; < 0.001), and had shorter length-of-stay (4.8 ± 2.0 vs. 7.0 ± 5.5 days; < 0.001). There was no difference in wound breakdown, seroma requiring intervention, hematoma, mesh infection, or recurrence; however, IS patients had decreased wound infections (2.0% vs. 8.6%; = 0.009), overall wound complications (11.4% vs. 21.1%; = 0.016), readmissions (2.7% vs. 13.0%; = 0.001), and reoperations (3.4% vs. 11.4%; = 0.007). Of MISR patients, 80.9% were IS and 19.1% were OOS. In contrast to OVHR, MISR IS and OOS patients had similar demographics, preoperative characteristics, intraoperative details, and postoperative outcomes. Although there were no differences in referred patients for MISR, this study demonstrates the racial disparities that exist among our IS and OOS complex, open AWR patients. Awareness of these disparities can help clinicians work towards equitable access to care and equal referrals to tertiary hernia centers.
PubMed: 38873344
DOI: 10.3389/jaws.2024.12946 -
International Journal For Parasitology.... Aug 2024To investigate infection of fish in the river system of Xinjiang (China), individuals were isolated from specimens of . Morphological characterization and phylogenetic...
To investigate infection of fish in the river system of Xinjiang (China), individuals were isolated from specimens of . Morphological characterization and phylogenetic analysis based on rDNA locus revealed that the gyrodactylids belong to new species. n. sp. differs significantly in the morphology of the haptoral structures from 12 known species of found in fishes of the subfamily Schizothoracinae. In particular, n. sp. has a relatively short dorsal bar with thick and large ends, flat and straight hamuli roots, and small ventral bar processes. Furthermore, . n. sp. is the only representative of found on Using the BLASTn search of rDNA sequences in GenBank and the Bayesian Information and Maximum Likelihood methods, we constructed phylogenetic trees for n. sp. As a result, our studies clearly identified that n. sp. was the first monogenean isolated from . and a new species belonged to the subgenus .
PubMed: 38873216
DOI: 10.1016/j.ijppaw.2024.100949 -
ENeuro Jun 2024CRISPR/Cas9 gene editing represents an exciting avenue to study genes of unknown function, and can be combined with genetically-encoded tools such as fluorescent...
CRISPR/Cas9 gene editing represents an exciting avenue to study genes of unknown function, and can be combined with genetically-encoded tools such as fluorescent proteins, channelrhodopsins, DREADDs, and various biosensors to more deeply probe the function of these genes in different cell types. However, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific editing across the nervous system. Expressing Cre-dependent Cas9 from a genomic locus affords space to package guide RNAs for gene editing together with Cre-dependent, genetically encoded tools to manipulate, map, or monitor neurons using a single virus.We validated this strategy with three common tools in neuroscience: ChRonos, a channelrhodopsin, for studying synaptic transmission using optogenetics; GCaMP8f for recording Ca2+ transients using photometry, and mCherry for tracing axonal projections. We tested these tools in multiple brain regions and cell types, including GABAergic neurons in the nucleus accumbens, glutamatergic neurons projecting from the ventral pallidum to the lateral habenula, dopaminergic neurons in the ventral tegmental area, and proprioceptive neurons in the periphery. This flexible approach could help identify and test the function of novel genes affecting synaptic transmission, circuit activity, or morphology with a single viral injection. Our CRISPR/Cas9 approach is the first to use a single vector to both knock-down genes of interest and express tools to monitor, map, and manipulate neurons. We demonstrate its utility in the central nervous system and describe the first systemic CRISPR/Cas9 gene editing with co-expressed reporters in the peripheral nervous system. Our approach fills a significant gap in the neuronal gene editing toolkit, allowing high-throughput study of genes of unknown function in the nervous system, and has broad utility for loss-of-function studies in other biological fields. This tool has great translational potential: it can be used to screen risk factor genes identified through genome-wide association studies, or knock-down native gene expression and reintroduce mutant variants identified in clinical settings.
PubMed: 38871457
DOI: 10.1523/ENEURO.0438-23.2024 -
PLoS Computational Biology Jun 2024Humans are extremely robust in our ability to perceive and recognize objects-we see faces in tea stains and can recognize friends on dark streets. Yet,...
Humans are extremely robust in our ability to perceive and recognize objects-we see faces in tea stains and can recognize friends on dark streets. Yet, neurocomputational models of primate object recognition have focused on the initial feed-forward pass of processing through the ventral stream and less on the top-down feedback that likely underlies robust object perception and recognition. Aligned with the generative approach, we propose that the visual system actively facilitates recognition by reconstructing the object hypothesized to be in the image. Top-down attention then uses this reconstruction as a template to bias feedforward processing to align with the most plausible object hypothesis. Building on auto-encoder neural networks, our model makes detailed hypotheses about the appearance and location of the candidate objects in the image by reconstructing a complete object representation from potentially incomplete visual input due to noise and occlusion. The model then leverages the best object reconstruction, measured by reconstruction error, to direct the bottom-up process of selectively routing low-level features, a top-down biasing that captures a core function of attention. We evaluated our model using the MNIST-C (handwritten digits under corruptions) and ImageNet-C (real-world objects under corruptions) datasets. Not only did our model achieve superior performance on these challenging tasks designed to approximate real-world noise and occlusion viewing conditions, but also better accounted for human behavioral reaction times and error patterns than a standard feedforward Convolutional Neural Network. Our model suggests that a complete understanding of object perception and recognition requires integrating top-down and attention feedback, which we propose is an object reconstruction.
Topics: Humans; Attention; Neural Networks, Computer; Pattern Recognition, Visual; Computational Biology; Models, Neurological; Recognition, Psychology
PubMed: 38870125
DOI: 10.1371/journal.pcbi.1012159 -
Spine Surgery and Related Research May 2024Studies describing the relationship between the hip and spine have reported that corrective spinal surgery for adult spinal deformity (ASD) affects the orientation of...
INTRODUCTION
Studies describing the relationship between the hip and spine have reported that corrective spinal surgery for adult spinal deformity (ASD) affects the orientation of the acetabulum. However, the extent to which spinal correction in ASD affects acetabular anteversion in the standing position is unclear, especially after total hip arthroplasty, for which dislocation is a concern. The purpose of this study was to evaluate changes in anterior acetabular coverage in the upright position due to extensive correction surgery for ASD.
METHODS
Thirty-six consecutive patients who had undergone spinal corrective surgery from the thoracolumbar region to the pelvis were enrolled and evaluated. The ventral-central-acetabular (VCA) angle and anterior acetabular head index (AAHI) were measured with a false-profile view to evaluate the relationship between acetabular anteversion in the standing position and spinopelvic parameters before and after surgery. The spinopelvic parameters measured included thoracic kyphosis, pelvic incidence, pelvic tilt (PT), sacral slope, lumbar lordosis (LL), sagittal vertical axis, and global tilt.
RESULTS
The VCA angle and AAHI were significantly increased after spinal deformity correction (p<0.001). The changes in LL and PT were correlated with the VCA angle (LL: right, ρ=0.56; left, ρ=0.55, p<0.001; PT: right, ρ=-0.59; left, ρ=-0.64, p<0.001) and AAHI (LL: right, ρ=0.51; left, ρ=0.58, p<0.01; PT: right, ρ=-0.52; left, ρ=-0.59, p<0.01), respectively. Linear regression analysis revealed that a 10° increase in LL results in 1.4°-1.9° and 1.6%-2% increases in the VCA angle and AAHI, respectively.
CONCLUSIONS
Surgical correction for ASD significantly affects sagittal spinopelvic parameters, resulting in increased acetabular anteversion. The anterior coverage of the acetabulum in the postoperative standing position could be predicted with the intraoperatively measured LL, and evaluation using a false-profile was considered useful for treating ASD, particularly in patients after total hip arthroplasty.
PubMed: 38868798
DOI: 10.22603/ssrr.2023-0273