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Nature Communications May 2024Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains...
Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains unclear. Here, we used optogenetics-assisted circuit mapping to identify how multiple top-down inputs from higher-order cortical and thalamic areas engage V1 excitatory and inhibitory neurons. Top-down inputs overlap in superficial layers yet segregate in deep layers. Inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) converge on L6 Pyrs, whereas ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) inputs are processed in parallel in Pyr-type-specific subnetworks (Pyr and Pyr) and drive mutual inhibition between them via local interneurons. Our study deepens understanding of the top-down modulation mechanisms of visual processing and establishes that V2M and ACA inputs in L6 employ integrated processing distinct from the parallel processing of LP and ORBvl inputs in L5.
Topics: Animals; Primary Visual Cortex; Optogenetics; Male; Thalamus; Visual Pathways; Neurons; Visual Cortex; Gyrus Cinguli; Interneurons; Visual Perception; Mice; Female; Brain Mapping
PubMed: 38802410
DOI: 10.1038/s41467-024-48924-8 -
Nature Communications May 2024How the spike output of the retina enables human visual perception is not fully understood. Here, we address this at the sensitivity limit of vision by correlating human...
How the spike output of the retina enables human visual perception is not fully understood. Here, we address this at the sensitivity limit of vision by correlating human visual perception with the spike outputs of primate ON and OFF parasol (magnocellular) retinal ganglion cells in tightly matching stimulus conditions. We show that human vision at its ultimate sensitivity limit depends on the spike output of the ON but not the OFF retinal pathway. Consequently, nonlinear signal processing in the retinal ON pathway precludes perceptual detection of single photons in darkness but enables quantal-resolution discrimination of differences in light intensity.
Topics: Animals; Humans; Retinal Ganglion Cells; Retina; Photons; Photic Stimulation; Visual Perception; Contrast Sensitivity; Male; Adult; Female; Primates; Visual Pathways; Macaca mulatta; Vision, Ocular
PubMed: 38802354
DOI: 10.1038/s41467-024-48750-y -
Cureus Apr 2024Introduction Erector spinae plane (ESP) block was first introduced for the management of thoracic pain but has become increasingly popular for the treatment of abdominal...
Introduction Erector spinae plane (ESP) block was first introduced for the management of thoracic pain but has become increasingly popular for the treatment of abdominal surgical pain. Previous studies have shown the ESP block can be easily adapted to abdominal procedures at the corresponding dermatome level and provide postoperative analgesia. Though the versatility, simplicity, and safety of the ESP block have been demonstrated, there is a gap in the literature regarding its comparison between thoracic and abdominal surgeries. This study aims to evaluate the efficacy of the ESP block in treating acute postoperative pain in patients undergoing thoracic and abdominal surgeries. Methods This retrospective study included 50 patients in the non-cardiac thoracic surgery group (bilateral breast mastectomy with reconstruction) and 50 patients in the abdominal surgery group (robotic or laparoscopic sleeve gastrectomy). Data was obtained via the acute pain service records at a tertiary care center from 2018 to 2022. All patients received bilateral ESP blocks, performed under ultrasound guidance. Various parameters were evaluated including oral morphine equivalents (OMEs) and visual analog scale (VAS) scores during post-anesthesia care unit (PACU), 6, 12, and 24 hours postop. The use of abortive antiemetic medications within 24 hours was also measured to evaluate the incidence of nausea and vomiting. The results were analyzed and compared. No control group is included, as all patients at our institution receive a peripheral nerve block as a part of the institution's enhanced recovery pathway (ERP). Results This retrospective study included 50 patients in the non-cardiac thoracic surgery group (bilateral breast mastectomy with reconstruction) and 50 patients in the abdominal surgery group (robotic or laparoscopic sleeve gastrectomy). Compared to the thoracic group, the abdominal group had a statistically higher VAS score in PACU with mean difference (MD) 1.3 VAS, 95% confidence interval (CI) 0.03-2.56, p-value 0.0443, statistically higher OME consumption in the PACU (difference 13.35 OME, 95% CI 4.97-21.73, p-value 0.0003), and required significantly more antiemetic pharmacotherapy (mean 1.4 antiemetics administered, 95% CI 0.84-2.04, p-value <0.0001). Despite the abdominal group having more OME utilization in the PACU, there was no difference in cumulative OME use in the first 24 hours (95% CI -9.745-24.10, p-value 0.4021). Conclusion In this study, we demonstrated that ESP blocks are an effective regional anesthesia technique to reduce postoperative pain and opioid consumption. The ESP block can serve as a useful and safe alternative to either thoracic epidural or paravertebral block techniques in thoracic and upper abdominal surgeries for perioperative pain management.
PubMed: 38800304
DOI: 10.7759/cureus.58926 -
IScience Jun 2024Type 1 cannabinoid receptors (CB1Rs) are expressed in major retinal neurons within the rod-pathway suggesting a role in regulating night visual processing, but the...
Type 1 cannabinoid receptors (CB1Rs) are expressed in major retinal neurons within the rod-pathway suggesting a role in regulating night visual processing, but the underlying mechanisms remain poorly understood. Using acute rat retinal slices, we show that CB1R activation reduces glutamate release from rod bipolar cell (RBC) axon terminals onto AII and A17 amacrine cells through a pathway that requires exchange proteins directly activated by cAMP (EPAC1/2) signaling. Consequently, CB1R activation abrogates reciprocal GABAergic feedback inhibition from A17 amacrine cells. Moreover, the activation of CB1Rs enhances and prolongs the time course of the dim-light rod-driven visual responses, an effect that was eliminated when both GABA and GABA receptors were blocked. Altogether, our findings underscore a non-canonical mechanism by which cannabinoid signaling regulates RBC dyad synapses in the inner retina to regulate dim-light visual responses to fine-tune night vision.
PubMed: 38799553
DOI: 10.1016/j.isci.2024.109920 -
Research Square May 2024In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information...
In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information flows through this hierarchy, neurons become progressively tuned to more complex image features. The circuit mechanisms and computations underlying the increasing complexity of these receptive fields (RFs) remain unidentified. To understand how this complexity emerges in the secondary visual area (V2), we investigated the functional organization of inputs from the primary visual cortex (V1) to V2 by combining retrograde anatomical tracing of these inputs with functional imaging of feature maps in macaque monkey V1 and V2. We found that V1 neurons sending inputs to single V2 orientation columns have a broad range of preferred orientations, but are strongly biased towards the orientation represented at the injected V2 site. For each V2 site, we then constructed a feedforward model based on the linear combination of its anatomically-identified large-scale V1 inputs, and studied the response proprieties of the generated V2 RFs. We found that V2 RFs derived from the linear feedforward model were either elongated versions of V1 filters or had spatially complex structures. These modeled RFs predicted V2 neuron responses to oriented grating stimuli with high accuracy. Remarkably, this simple model also explained the greater selectivity to naturalistic textures of V2 cells compared to their V1 input cells. Our results demonstrate that simple linear combinations of feedforward inputs can account for the orientation selectivity and texture sensitivity of V2 RFs.
PubMed: 38798339
DOI: 10.21203/rs.3.rs-4139501/v1 -
Early Eye Disengagement Is Regulated by Task Complexity and Task Repetition in Visual Tracking Task.Sensors (Basel, Switzerland) May 2024Understanding human actions often requires in-depth detection and interpretation of bio-signals. Early eye disengagement from the target (EEDT) represents a significant...
Understanding human actions often requires in-depth detection and interpretation of bio-signals. Early eye disengagement from the target (EEDT) represents a significant eye behavior that involves the proactive disengagement of the gazes from the target to gather information on the anticipated pathway, thereby enabling rapid reactions to the environment. It remains unknown how task difficulty and task repetition affect EEDT. We aim to provide direct evidence of how these factors influence EEDT. We developed a visual tracking task in which participants viewed arrow movement videos while their eye movements were tracked. The task complexity was increased by increasing movement steps. Every movement pattern was performed twice to assess the effect of repetition on eye movement. Participants were required to recall the movement patterns for recall accuracy evaluation and complete cognitive load assessment. EEDT was quantified by the fixation duration and frequency within the areas of eye before arrow. When task difficulty increased, we found the recall accuracy score decreased, the cognitive load increased, and EEDT decreased significantly. The EEDT was higher in the second trial, but significance only existed in tasks with lower complexity. EEDT was positively correlated with recall accuracy and negatively correlated with cognitive load. Performing EEDT was reduced by task complexity and increased by task repetition. EEDT may be a promising sensory measure for assessing task performance and cognitive load and can be used for the future development of eye-tracking-based sensors.
Topics: Humans; Male; Eye Movements; Female; Eye-Tracking Technology; Adult; Young Adult; Task Performance and Analysis; Cognition; Fixation, Ocular
PubMed: 38793839
DOI: 10.3390/s24102984 -
International Journal of Molecular... May 2024Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and,...
Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.
Topics: Humans; Female; Extracellular Vesicles; Pregnancy; Placenta; Placenta Accreta; Biomarkers; Adult; MicroRNAs; Placenta Previa; Alkaline Phosphatase; Isoenzymes; GPI-Linked Proteins
PubMed: 38791142
DOI: 10.3390/ijms25105102 -
Antioxidants (Basel, Switzerland) May 2024Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular... (Review)
Review
Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.
PubMed: 38790699
DOI: 10.3390/antiox13050594 -
Antioxidants (Basel, Switzerland) Apr 2024Oxidative stress forms part of the molecular basis contributing to the development and manifestation of myopia, a refractive error with associated pathology that is...
Oxidative stress forms part of the molecular basis contributing to the development and manifestation of myopia, a refractive error with associated pathology that is increasingly prevalent worldwide and that subsequently leads to an upsurge in degenerative visual impairment due to conditions that are especially associated with high myopia. The purpose of our study was to examine the interrelation of potential oxidative-stress-related metabolites found in the aqueous humor of high-myopic, low-myopic, and non-myopic patients within a clinical study. We conducted a cross-sectional study, selecting two sets of patients undergoing cataract surgery. The first set, which was used to analyze metabolites through an NMR assay, comprised 116 patients. A total of 59 metabolites were assigned and quantified. The PLS-DA score plot clearly showed a separation with minimal overlap between the HM and control samples. The PLS-DA model allowed us to determine 31 major metabolite differences in the aqueous humor of the study groups. Complementary statistical analysis of the data allowed us to determine six metabolites that presented significant differences among the experimental groups ( < 005). A significant number of these metabolites were discovered to have a direct or indirect connection to oxidative stress linked with conditions of myopic eyes. Notably, we identified metabolites associated with bioenergetic pathways and metabolites that have undergone methylation, along with choline and its derivatives. The second set consisted of 73 patients who underwent a glutathione assay. Here, we showed significant variations in both reduced and oxidized glutathione in aqueous humor among all patient groups ( < 0.01) for the first time. Axial length, refractive status, and complete ophthalmologic examination were also recorded, and interrelations among metabolic and clinical parameters were evaluated.
PubMed: 38790644
DOI: 10.3390/antiox13050539 -
Biomolecules Apr 2024In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract... (Review)
Review
In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations.
Topics: Humans; Neuroanatomical Tract-Tracing Techniques; Carbocyanines; Central Nervous System; Peripheral Nervous System; Fluorescent Dyes
PubMed: 38785943
DOI: 10.3390/biom14050536