Anatomical Connections Research Articles

Anatomical Connectivity Constrains Dynamic Functional Connectivity among Neural Systems: Implications for Cognition and Behavior

Abstract Leslie Ungerleider had a tremendous impact across many different areas of cognitive neuroscience. Her ideas and her approach, as well as her findings, will continue to impact the field for generations to come. One of the most impactful aspects of her approach was her focus on the ways that anatomical connections constrain functional communications among brain regions. Furthermore, she emphasized that changes in these functional communications, whether from lesions to the anatomical connections or temporary modulations of the efficacy of information transmission resulting from selective attention, have consequences for cognition and behavior. By necessity, this short review cannot cover the vast amount of research that contributed to or benefited from Leslie's work. Rather, we focus on one line of research that grew directly from some of Leslie's early work and her mentoring on these important concepts. This research and the many other lines of research that arose from these same origins has helped develop our understanding of the visual system, and cognitive systems more generally, as collections of highly organized, specialized, dynamic, and interacting subsystems.

Reward system activation improves recovery from acute myocardial infarction

Abstract Introduction Psychological processes play a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here, we focused on the reward system, which mediates positively valenced emotions, motivation, and expectation and is based mainly on dopaminergic neurotransmission from the ventral tegmental area (VTA). Purpose The study examines the impact of activating dopaminergic neurons in the VTA following AMI in mice, aiming to understand the extent and mechanisms through which motivational brain network contribute to cardiac recovery process. Methods We used Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) to target neuronal activity. We performed an AMI model and assessed cardiac function using cardiac magnetic resonance (CMR). We used histology, immunohistochemistry, proteomic analysis, ELISA, reverse transcription-PCR, endothelial tube formation assay, and pseudorabies-virus neuronal tracing to investigate the mechanism. Results Chemogenetic activation of dopaminergic neurons in the VTA significantly modified the remodeling processes by reducing scar tissue (Fig. 1a) and increased vascularization (Fig. 1b) 15 days following AMI, leading to improved left-ventricular performance compared to control (Fig. 1c). These effects were mediated through several physiological mechanisms, including alterations in immune activity, and reduced adrenergic inputs to the liver. We further demonstrate an anatomical connection between the VTA and the liver that follows AMI manifested by altered transcription of complement component 3 (C3). We established the essential role of C3 in endothelial tube formation in vitro and its necessity in the beneficial effects of VTA activation on the recovery from AMI in vivo (Fig.2). Conclusion These findings establish a causal connection between a motivational brain network and recovery from AMI, introducing potential new therapeutic avenues for intervention.Effects of VTA activation on cardiac recMechanism of VTA effects

A Deep Learning-based Pipeline for Segmenting the Cerebral Cortex Laminar Structure in Histology Images.

Characterizing the anatomical structure and connectivity between cortical regions is a critical step towards understanding the information processing properties of the brain and will help provide insight into the nature of neurological disorders. A key feature of the mammalian cerebral cortex is its laminar structure. Identifying these layers in neuroimaging data is important for understanding their global structure and to help understand the connectivity patterns of neurons in the brain. We studied Nissl-stained and myelin-stained slice images of the brain of the common marmoset (Callithrix jacchus), which is a new world monkey that is becoming increasingly popular in the neuroscience community as an object of study. We present a novel computational framework that first acquired the cortical labels using AI-based tools followed by a trained deep learning model to segment cerebral cortical layers. We obtained a Euclidean distance of for the cortical labels acquisition, which was in the acceptable range by computing the half Euclidean distance of the average cortex thickness ( ). We compared our cortical layer segmentation pipeline with the pipeline proposed by Wagstyl et al. (PLoS biology, 18(4), e3000678 2020) adapted to 2D data. We obtained a better mean percentile Hausdorff distance (95HD) of . Whereas a mean 95HD of was obtained from Wagstyl et al. We also compared our pipeline's performance against theirs using their dataset (the BigBrain dataset). The results also showed better segmentation quality, Jaccard Index acquired from our pipeline, while was stated in their paper.

Assessment of the Depiction of Superficial White Matter Using Ultra-High-Resolution Diffusion MRI.

The superficial white matter (SWM) consists of numerous short-range association fibers connecting adjacent and nearby gyri and plays an important role in brain function, development, aging, and various neurological disorders. Diffusion MRI (dMRI) tractography is an advanced imaging technique that enables in vivo mapping of the SWM. However, detailed imaging of the small, highly-curved fibers of the SWM is a challenge for current clinical and research dMRI acquisitions. This work investigates the efficacy of mapping the SWM using in vivo ultra-high-resolution dMRI data. We compare the SWM mapping performance from two dMRI acquisitions: a high-resolution 0.76-mm isotropic acquisition using the generalized slice-dithered enhanced resolution (gSlider) protocol and a lower resolution 1.25-mm isotropic acquisition obtained from the Human Connectome Project Young Adult (HCP-YA) database. Our results demonstrate significant differences in the cortico-cortical anatomical connectivity that is depicted by these two acquisitions. We perform a detailed assessment of the anatomical plausibility of these results with respect to the nonhuman primate (macaque) tract-tracing literature. We find that the high-resolution gSlider dataset is more successful at depicting a large number of true positive anatomical connections in the SWM. An additional cortical coverage analysis demonstrates significantly higher cortical coverage in the gSlider dataset for SWM streamlines under 40 mm in length. Overall, we conclude that the spatial resolution of the dMRI data is one important factor that can significantly affect the mapping of SWM. Considering the relatively long acquisition time, the application of dMRI tractography for SWM mapping in future work should consider the balance of data acquisition efforts and the efficacy of SWM depiction.

Decoding sound content in the early visual cortex of aphantasic participants.

Listening to natural auditory scenes leads to distinct neuronal activity patterns in the early visual cortex (EVC) of blindfolded sighted and congenitally blind participants.1,2 This pattern of sound decoding is organized by eccentricity, with the accuracy of auditory information increasing from foveal to far peripheral retinotopic regions in the EVC (V1, V2, and V3). This functional organization by eccentricity is predicted by primate anatomical connectivity,3,4 where cortical feedback projections from auditory and other non-visual areas preferentially target the periphery of early visual areas. In congenitally blind participants, top-down feedback projections to the visual cortex proliferate,5 which might account for even higher sound-decoding accuracy in the EVC compared with blindfolded sighted participants.2 In contrast, studies in participants with aphantasia suggest an impairment of feedback projections to early visual areas, leading to a loss of visual imagery experience.6,7 This raises the question of whether impaired visual feedback pathways in aphantasia also reduce the transmission of auditory information to early visual areas. We presented auditory scenes to 23 blindfolded aphantasic participants. We found overall decreased sound decoding in early visual areas compared to blindfolded sighted ("control") and blind participants. We further explored this difference by modeling eccentricity effects across the blindfolded control, blind, and aphantasia datasets, and with a whole-brain searchlight analysis. Our findings suggest that the feedback of auditory content to the EVC is reduced in aphantasic participants. Reduced top-down projections might lead to both less sound decoding and reduced subjective experience of visual imagery.

Investigating Cerebello-Frontal Circuits Associated with Emotional Prosody: A Double-Blind tDCS and fNIRS study.

The emotional and cognitive cerebellum has been explored by several studies in the past years. Recent evidence suggested the possible contribution of the cerebellum in processing emotional prosody, namely the ability to comprehend the emotional content of a given vocal utterance, likely mediated by anatomical and functional cerebello-prefrontal connections. In the present study, the involvement of a functional cerebello-prefrontal network in recognising emotional prosody was assessed by combining non-invasive anodal transcranial direct current stimulation (tDCS) over the right or the left cerebellum and functional Near Infrared Spectroscopy of the prefrontal cortex, in a double-blind within-subject experimental design on healthy participants. The results showed that right and, to a less extent, left cerebellar tDCS (as compared to sham stimulation) reduced neural activation in the prefrontal cortex while accuracy and reaction times at the vocal recognition task remained unchanged. These findings highlight functional properties of the cerebello-frontal connections and the psychophysiological effects of cerebellar brain stimulation, with possible clinical applications in psychiatric and neurological conditions.

Musicianship and Prominence of Interhemispheric Connectivity Determine Two Different Pathways to Atypical Language Dominance.

During infancy and adolescence, language develops from a predominantly interhemispheric control-through the corpus callosum (CC)-to a predominantly intrahemispheric control, mainly subserved by the left arcuate fasciculus (AF). Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from the auditory cortex to the inferior frontal cortex when contrasting speech to tone perception and an enhanced interhemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Nonmusicians present a relation between atypical lateralization and intrahemispheric underdevelopment across the anterior AF, hinting at a dysregulation of the ontogenetic shift from an interhemispheric to an intrahemispheric brain. Musicians reveal an alternative pathway related to interhemispheric overdevelopment across the posterior CC and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions.

Immune mediators in heart-lung communication.

It is often the case that serious, end-stage manifestations of disease result from secondary complications in organs distinct from the initial site of injury or infection. This is particularly true of diseases of the heart-lung axis, given the tight anatomical connections of the two organs within a common cavity in which they collectively orchestrate the two major, intertwined circulatory pathways. Immune cells and the soluble mediators they secrete serve as effective, and targetable, messengers of signals between different regions of the body but can also contribute to the spread of pathology. In this review, we discuss the immunological basis of interorgan communication between the heart and lung in various common diseases, and in the context of organ crosstalk more generally. Gaining a greater understanding of how the heart and lung communicate in health and disease, and viewing disease progression generally from a more holistic, whole-body viewpoint have the potential to inform new diagnostic approaches and strategies for better prevention and treatment of comorbidities.

White matter microstructure and functional connectivity in the brains of infants with Turner syndrome.

Turner syndrome, caused by complete or partial loss of an X-chromosome, is often accompanied by specific cognitive challenges. Magnetic resonance imaging studies of adults and children with Turner syndrome suggest these deficits reflect differences in anatomical and functional connectivity. However, no imaging studies have explored connectivity in infants with Turner syndrome. Consequently, it is unclear when in development connectivity differences emerge. To address this gap, we compared functional connectivity and white matter microstructure of 1-year-old infants with Turner syndrome to typically developing 1-year-old boys and girls. We examined functional connectivity between the right precentral gyrus and five regions that show reduced volume in 1-year old infants with Turner syndrome compared to controls and found no differences. However, exploratory analyses suggested infants with Turner syndrome have altered connectivity between right supramarginal gyrus and left insula and right putamen. To assess anatomical connectivity, we examined diffusivity indices along the superior longitudinal fasciculus and found no differences. However, an exploratory analysis of 46 additional white matter tracts revealed significant group differences in nine tracts. Results suggest that the first year of life is a window in which interventions might prevent connectivity differences observed at later ages, and by extension, some of the cognitive challenges associated with Turner syndrome.

Multimodal Connectivity-Based Individual Parcellation and Analysis for Humans and Rhesus Monkeys.

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches have examined single modalities of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress

Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit.

Comparison of data-driven thresholding methods using directed functional brain networks.

Over the past two centuries, intensive empirical research has been conducted on the human brain. As an electroencephalogram (EEG) records millisecond-to-millisecond changes in the electrical potentials of the brain, it has enormous potential for identifying useful information about neuronal transactions. The EEG data can be modelled as graphs by considering the electrode sites as nodes andthe linear and nonlinear statistical dependencies among them as edges (with weights). The graph theoretical modelling of EEG data results in functional brain networks (FBNs), which are fully connected (complete) weighted undirected/directed networks. Since various brain regions are interconnected via sparse anatomical connections, the weak links can be filtered out from the fullyconnected networks using a process called thresholding. Multiple researchers in the past decades proposed many thresholding methods to gather more insights about the influential neuronal connections of FBNs. This paper reviews various thresholding methods used in the literature for FBN analysis. The analysis showed that data-driven methods are unbiased since no arbitrary user-specified threshold is required. The efficacy of four data-driven thresholding methods, namely minimum spanning tree (MST), minimum connected component (MCC), union of shortest path trees (USPT), and orthogonal minimum spanning tree (OMST), in characterizing cognitive behavior of the normal human brain is analysed using directed FBNs constructed from EEG data of different cognitive load states. The experimental results indicate that both MCC and OMST thresholding methods can detect cognitive load-induced changes in the directed functional brain networks.

Massive offerings of marine fish at Salango, coastal Ecuador, during the Middle Guangala phase (AD 300–600)

The Ecuadorian site of Salango, with its 5500 years of pre-Columbian history, is of fundamental interest for understanding the relationships between people and the sea on the tropical Pacific coast of South America. In 2015, thousands of fish remains were found in foundational offering deposits of a perimeter wall built to protect a sanctuary of the Middle Guangala phase (AD 300–600). Approximately 3300 bones have been identified, and these represent the remains of 337 individuals belonging to 49 different species. The assemblage is largely dominated by pelagic species, particularly scombrids weighing 2–3 kg. The presence of dolphinfish, a taxon that has not been reported previously in the archaeological record of Salango, supports the hypothesis that fishing was mainly conducted offshore by boat. The preservation in situ of numerous anatomical connections and the large number of remains found virtually intact suggest that these fish were deposited whole. We suggest that these deposits were designed to represent the specific marine environment being exploited from Salango and, more broadly, the sea itself. In this respect, Salango presents an unusual manifestation of pre-Columbian sea-oriented ritual practice so far unique on the Ecuadorian coast.

Time cells in the retrosplenial cortex.

The retrosplenial cortex (RSC) is a key component of the brain's memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In this study, we reanalyzed archival RSC neuronal firing data during the intertrial delay period from two previous experiments involving different behavioral tasks, a blocked alternation task and a cued T-maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T-maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off-response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T-maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory.

Transthalamic Pathways for Cortical Function.

The cerebral cortex contains multiple, distinct areas that individually perform specific computations. A particular strength of the cortex is the communication of signals between cortical areas that allows the outputs of these compartmentalized computations to influence and build on each other, thereby dramatically increasing the processing power of the cortex and its role in sensation, action, and cognition. Determining how the cortex communicates signals between individual areas is, therefore, critical for understanding cortical function. Historically, corticocortical communication was thought to occur exclusively by direct anatomical connections between areas that often sequentially linked cortical areas in a hierarchical fashion. More recently, anatomical, physiological, and behavioral evidence is accumulating indicating a role for the higher-order thalamus in corticocortical communication. Specifically, the transthalamic pathway involves projections from one area of the cortex to neurons in the higher-order thalamus that, in turn, project to another area of the cortex. Here, we consider the evidence for and implications of having two routes for corticocortical communication with an emphasis on unique processing available in the transthalamic pathway and the consequences of disorders and diseases that affect transthalamic communication.

Correlated variability and its attentional modulation depend on anatomical connectivity

Visual cortical neurons show variability in their responses to repeated presentations of a stimulus and a portion of this variability is shared across neurons. Attention may enhance visual perception by reducing shared spiking variability. However, shared variability and its attentional modulation are not consistent within or across cortical areas, and depend on additional factors such as neuronal type. A critical factor that has not been tested is actual anatomical connectivity. We measured spike count correlations among pairs of simultaneously recorded neurons in the primary visual cortex (V1) for which anatomical connectivity was inferred from spiking cross-correlations. Neurons were recorded in monkeys performing a contrast-change discrimination task requiring covert shifts in visual spatial attention. Accordingly, spike count correlations were compared across trials in which attention was directed toward or away from the visual stimulus overlapping recorded neuronal receptive fields. Consistent with prior findings, attention did not significantly alter spike count correlations among random pairings of unconnected V1 neurons. However, V1 neurons connected via excitatory synapses showed a significant reduction in spike count correlations with attention. Interestingly, V1 neurons connected via inhibitory synapses demonstrated high spike count correlations overall that were not modulated by attention. Correlated variability in excitatory circuits also depended upon neuronal tuning for contrast, the task-relevant stimulus feature. These results indicate that shared variability depends on the type of connectivity in neuronal circuits. Also, attention significantly reduces shared variability in excitatory circuits, even when attention effects on randomly sampled neurons within the same area are weak.

TS-AI: A deep learning pipeline for multimodal subject-specific parcellation with task contrasts synthesis

Accurate mapping of brain functional subregions at an individual level is crucial. Task-based functional MRI (tfMRI) captures subject-specific activation patterns during various functions and behaviors, facilitating the individual localization of functionally distinct subregions. However, acquiring high-quality tfMRI is time-consuming and resource-intensive in both scientific and clinical settings. The present study proposes a two-stage network model, TS-AI, to individualize an atlas on cortical surfaces through the prediction of tfMRI data. TS-AI first synthesizes a battery of task contrast maps for each individual by leveraging tract-wise anatomical connectivity and resting-state networks. These synthesized maps, along with feature maps of tract-wise anatomical connectivity and resting-state networks, are then fed into an end-to-end deep neural network to individualize an atlas. TS-AI enables the synthesized task contrast maps to be used in individual parcellation without the acquisition of actual task fMRI scans. In addition, a novel feature consistency loss is designed to assign vertices with similar features to the same parcel, which increases individual specificity and mitigates overfitting risks caused by the absence of individual parcellation ground truth. The individualized parcellations were validated by assessing test-retest reliability, homogeneity, and cognitive behavior prediction using diverse reference atlases and datasets, demonstrating the superior performance and generalizability of TS-AI. Sensitivity analysis yielded insights into region-specific features influencing individual variation in functional regionalization. Additionally, TS-AI identified accelerated shrinkage in the medial temporal and cingulate parcels during the progression of Alzheimer's disease, suggesting its potential in clinical research and applications.

Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training.

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections.

Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Retina-Brain Homology: The Correlation Between Ophthalmic or Retinal Artery Occlusion and Ischemic Stroke.

The retina's similar structure and function to the brain make it a unique visual "window" for studying cerebral disorders. Ophthalmic artery occlusion (OAO) or retinal artery occlusion (RAO) is a severe ophthalmic emergency that significantly affects visual acuity. Studies have demonstrated that patients with OAO or RAO face a notably higher risk of future acute ischemic stroke (AIS). However, ophthalmologists often overlook multidisciplinary approach involving the neurologist, to evaluate the risk of AIS and devise clinical treatment strategies for patients with OAO or RAO. Unlike the successful use of thrombolysis in AIS, the application of thrombolysis for OAO or RAO remains limited and controversial due to insufficient reliable evidence. In this review, we aim to summarize the anatomical and functional connections between the retina and the brain, and the clinical connection between OAO or RAO and AIS, compare and review recent advances in the effectiveness and safety of intravenous and intra-arterial thrombolysis therapy in patients with OAO or RAO, and discuss future research directions for OAO or RAO. Our goal is to advance the development of multidisciplinary diagnosis and treatment strategies for the disease, as well as to establish expedited pathways or thrombolysis guidelines for vascular intervention.