manual-segmentation-of-the-human-choroid-plexus-using-brain-mri

Manual Segmentation of the Human Choroid Plexus Using Brain MRI

The choroid plexus has been implicated in neurodevelopment and a range of brain disorders. Evidence demonstrates that the choroid plexus is critical for ...

Beth Israel Deaconess Medical Center

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by reductions in gray matter and white matter. Limitations in brain imaging have led researchers to use optical coherence tomography (OCT) to explore retinal imaging biomarkers of brain pathology. We examine the retinal layers that may be associated with SZ or BD.

A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder.

Commentary: Can retinal imaging biomarkers inform psychosis pathophysiology?

Studies utilizing optical coherence tomography (OCT) in psychosis have identified abnormalities in retinal cytoarchitecture. We aim to analyze retinal layer topography in psychosis and its correlation with clinical and imaging parameters. Macular retinal images were obtained via OCT in psychosis probands (n = 25) and healthy controls (HC, n = 15). Clinical, cognitive and structural MRI data were collected from participants. No thinning was noted for the retinal nerve fiber, ganglion cell or inner plexiform layers. We found significant thinning in the right inner temporal, right central, and left inner superior quadrants of the outer nuclear layer (ONL) in probands compared to HC. Thickening of the outer plexiform layer (OPL) was observed in the right inner temporal, left inner superior, and left inner temporal quadrants. The right inner temporal and left inner superior quadrants of both the OPL and ONL showed significant inverse correlations. Retinal pigment epithelium thinning correlated with worse mania symptoms, and thinning in the ONL was associated with worse cognitive function. ONL thinning was also associated with smaller total brain and white matter volume. Our findings suggest that outer retinal layers may provide additional insights into the pathophysiology of psychosis, possibly reflecting synaptic or inflammatory aberrations that lead to retinal pathologies.

Retinal layer abnormalities and their association with clinical and brain measures in psychotic disorders: A preliminary study.

Identifying retinal layer endophenotypes for schizophrenia.

Visual perceptual and processing deficits are common in schizophrenia and possibly point towards visual pathway alterations. However, no studies have examined visual cortical morphology in first-episode psychosis (FEP). In an antipsychotic-naïve FEP population, we investigated primary visual (V1), association area (V2), and motion perception (V5/MT) morphology compared to controls. We found reductions in the V1 and V2 areas, greater MT area and lower MT thickness in the FEP-schizophrenia group when compared to controls. Also, lower MT thickness was associated with worse negative symptoms. Our results shed light on this poorly studied area of visual cortex morphology in FEP.

Visual Cortical Alterations and their Association with Negative Symptoms in Antipsychotic-Naïve First Episode Psychosis.

Neuroimaging considerations when investigating choroid plexus morphology in idiopathic psychosis.

Theory of Mind (ToM) refers to the ability to perceive others' mental states. Lower ToM has often been associated with poorer functional outcomes in schizophrenia, making it an important treatment target. However, little is known about the underlying neural mechanisms associated with ToM impairments in early course schizophrenia. This study aimed to validate the False Belief task to measure ToM in schizophrenia and to identify aberrant brain activity associated with impairments. 36 individuals with early course schizophrenia and 17 controls were administered the Hinting Task and performed a functional magnetic resonance imaging (fMRI) False Belief task. Between-group differences were examined in a priori regions of interest (ROIs) known to be associated with ToM tasks: medial prefrontal cortex, ventral medial prefrontal cortex, and both the left and right temporal parietal junction (TPJ). We observed a significant positive association between Hinting Task performance and False Belief accuracy, validating the False Belief task as a measure of ToM. Compared to controls, individuals with schizophrenia exhibited reduced brain activation in all four ROIs during the fMRI False Belief task. Furthermore, task-related activations in bilateral TPJs were shown to be positively associated with ToM abilities regardless of diagnosis. Individuals with schizophrenia with lower performance on the False Belief task showed significant reductions in task-related activation in the bilateral TPJ compared to controls, while reductions were not significant for those with higher performance. Our findings suggest that lower neural activity in the bilateral TPJ are associated with ToM impairments observed in individuals with early course schizophrenia.

Theory of Mind impairments in early course schizophrenia: An fMRI study.

Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ.

Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography.

Peripheral inflammation is implicated in schizophrenia, however, not all individuals demonstrate inflammatory alterations. Recent studies identified inflammatory subtypes in chronic psychosis with high inflammation having worse cognitive performance and displaying neuroanatomical enlargement compared to low inflammation subtypes. It is unclear if inflammatory subtypes exist earlier in the disease course, thus, we aim to identify inflammatory subtypes in antipsychotic naïve First-Episode Schizophrenia (FES).

Inflammatory Subtypes in Antipsychotic-Naïve First-Episode Schizophrenia are Associated with Altered Brain Morphology and Topological Organization.

Sleep abnormalities are an early feature of schizophrenia (SZ) characterized by reductions in sleep spindles that are associated with deficits in brain connectivity and cognitive function. This study investigated sleep spindle density (SSD) differences between SZ, first episode psychosis (FEP), and family high-risk (FHR) populations and matched healthy controls (HC) by investigating recent studies via a meta-analysis. We collected experimental, demographic, and methodological metrics from eligible studies across multiple online databases. 14 total studies survived the inclusion and exclusion criteria for a total of 337 patients and relatives and 339 HC. R-Studio was used to run the meta-analysis via the meta and metaphor packages. A heterogeneity score of I = 80% was calculated and thus a random effects model was chosen. We report a large effect size for SSD in patients compared to controls. Furthermore, illness duration was significantly associated with SSD. Our next step to understanding sleep spindles would be to investigate SSD's use as a predictor for SZ or attempt to normalize SSD deficits as a therapeutic option.

Investigating sleep spindle density and schizophrenia: A meta-analysis.

To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA).

Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography.

Impairments of the visual system are implicated in psychotic disorders. However, studies exploring visual cortex (VC) morphology in this population are limited. Using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, we examined VC structure in psychosis probands and their first-degree relatives (RELs), sex differences in VC measures, and their relationships with cognitive and peripheral inflammatory markers.

Regional and Sex-Specific Alterations in the Visual Cortex of Individuals With Psychosis Spectrum Disorders.

While structural changes within the retina of psychosis patients have been established, no detailed studies of choroidal microvasculature in these patients have been performed. Given evidence of microvascular disruption in psychosis patients, this study sought to determine whether there exists evidence of microvascular disruption in the choroids in these patients.

Sex-Specific Changes in Choroid Vasculature Among Patients with Schizophrenia and Bipolar Disorder.

Transcranial electrical stimulation (tES) may improve psychosis symptoms, but few investigations have targeted brain regions causally linked to psychosis symptoms. We implemented a novel montage targeting the extrastriate visual cortex (eVC) previously identified by lesion network mapping in the manifestation of visual hallucinations.

A pilot study to investigate the efficacy and tolerability of lesion network guided transcranial electrical stimulation in outpatients with psychosis spectrum illness.

Although there is convergent evidence for blood-brain barrier (BBB) dysfunction and peripheral inflammation in schizophrenia (SZ) and bipolar disorder (BD), it is unknown whether BBB deficits are intrinsic to brain microvascular endothelial cells (BMECs) or arise via effects of peripheral inflammatory cytokines. We examined BMEC function using stem cell-based models to identify cellular and molecular deficits associated with BBB dysfunction in SZ and BD. Induced pluripotent stem cells (iPSCs) from 4 SZ, 4 psychotic BD and 4 healthy control (HC) subjects were differentiated into BMEC-"like" cells. Gene expression and protein levels of tight junction proteins were assessed. Transendothelial electrical resistance (TEER) and permeability were assayed to evaluate BBB function. Cytokine levels were measured from conditioned media. BMECs derived from human iPSCs in SZ and BD did not show differences in BBB integrity or permeability compared to HC BMECs. Outlier analysis using TEER revealed a BBB-deficit (n = 3) and non-deficit (n = 5) group in SZ and BD lines. Stratification based on BBB function in SZ and BD patients identified a BBB-deficit subtype with reduced barrier function, tendency for increased permeability to smaller molecules, and decreased claudin-5 (CLDN5) levels. BMECs from the BBB-deficit group show increased matrix metallopeptidase 1 (MMP1) activity, which correlated with reduced CLDN5 and worse BBB function, and was improved by tumor necrosis factor α (TNFα) and MMP1 inhibition. These results show potential deficits in BMEC-like cells in psychotic disorders that result in BBB disruption and further identify TNFα and MMP1 as promising targets for ameliorating BBB deficits.

Article	Year
A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder. Schizophrenia bulletin\| PubMed ID: 31112601
Commentary: Can retinal imaging biomarkers inform psychosis pathophysiology? Schizophrenia research\| PubMed ID: 31668491	2020
Retinal layer abnormalities and their association with clinical and brain measures in psychotic disorders: A preliminary study. Psychiatry research. Neuroimaging\| PubMed ID: 32145500	2020
Identifying retinal layer endophenotypes for schizophrenia. Schizophrenia research\| PubMed ID: 32247746	2020
Visual Cortical Alterations and their Association with Negative Symptoms in Antipsychotic-Naïve First Episode Psychosis. Psychiatry research\| PubMed ID: 32325384
Neuroimaging considerations when investigating choroid plexus morphology in idiopathic psychosis. Schizophrenia research\| PubMed ID: 32732088	2020
Theory of Mind impairments in early course schizophrenia: An fMRI study. Journal of psychiatric research\| PubMed ID: 33621908	2021
Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography. Schizophrenia bulletin\| PubMed ID: 34554256
Inflammatory Subtypes in Antipsychotic-Naïve First-Episode Schizophrenia are Associated with Altered Brain Morphology and Topological Organization. Brain, behavior, and immunity\| PubMed ID: 34875344
Investigating sleep spindle density and schizophrenia: A meta-analysis. Psychiatry research\| PubMed ID: 34922240
Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie\| PubMed ID: 35678840
Regional and Sex-Specific Alterations in the Visual Cortex of Individuals With Psychosis Spectrum Disorders. Biological psychiatry\| PubMed ID: 35688762
Sex-Specific Changes in Choroid Vasculature Among Patients with Schizophrenia and Bipolar Disorder. Clinical ophthalmology (Auckland, N.Z.)\| PubMed ID: 35924185
A pilot study to investigate the efficacy and tolerability of lesion network guided transcranial electrical stimulation in outpatients with psychosis spectrum illness. Asian journal of psychiatry\| PubMed ID: 37633159	2023
Brain microvascular endothelial cells and blood-brain barrier dysfunction in psychotic disorders. Molecular psychiatry\| PubMed ID: 37730841	2023

Deepthi Bannai

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