Biology subjects

Campos, V. P.

Publications and source records attributed to Campos, V. P..

5 recordsLinked to original sources

bioRxiv2026

Noninvasive Focal Gene Delivery of Functional Neural Actuators to the Primate Spinal Cord using Focused Ultrasound

Pathologies of the spinal cord -- from degenerative diseases to chronic pain -- represent a substantial global health burden. Although surgical and pharmacological treatments for spinal cord pathologies have advanced considerably, therapies capable of addressing the cellular mechanisms underlying these conditions remain limited. Viral gene therapies present a compelling alternative, allowing for delivery of therapeutic genes that directly target the pathological processes in specific cell-types. Effective viral delivery to the spinal cord, however, remains constrained by a fundamental tradeoff between procedural invasiveness and spatial precision. As such, there remains a need for clinically tractable methods -- that are both noninvasive and focal -- to deliver gene therapeutics across the restrictive vascular boundaries of the blood-spinal cord barrier (BSCB). Here, we demonstrate noninvasive, focal disruption of the BSCB and delivery of systemically administered chemogenetic gene payloads to the cervical and thoracic spinal cord in marmoset nonhuman primates (Callithrix jacchus) using focused ultrasound (FUS). Through systematic testing of ultrasonic pressures and central frequencies, we establish a FUS parameter set optimized for robust, spatially constrained molecular delivery across the marmoset BSCB. Using these optimized parameters, we show that FUS BSCB disruption permitted focal penetrance of systemically administered viral vectors for transduction of both fluorescent transgenes and excitatory chemogenetics within targeted spinal segments. Positron emission tomography (PET) imaging following chemogenetic actuation revealed significantly increased metabolic demand within the targeted region of the spinal cord, demonstrating in vivo evidence of functional transgene expression. Behavioral and histopathological assessments demonstrated preserved neurological function and tissue integrity, supporting the safety of FUS BSCB disruption and viral delivery in nonhuman primates. To facilitate broad application of this platform for noninvasive delivery of receptor-based gene therapeutics in marmosets, we generated an ultra-high-resolution (74 m) multimodal MRI/CT spinal cord template for precise targeting and anatomical localization. We also provide open-access engineering drawings and CAD files for our M-FRAME system (Marmoset Fixation and Reorientation Apparatus for Multimodal Experiments), enabling precise and repeatable spinal targeting without surgical fixation. Together, these results establish FUS-mediated BSCB disruption as a safe and effective approach for noninvasive, focal gene delivery to the primate spinal cord.

neuroscience↗

bioRxiv2026

Apparent Anatomical Variability Through Rigid Augmentation Enables Reliable Corpus Callosum Segmentation

The corpus callosum is a major white matter bundle responsible for connecting both hemispheres. In mammals, due to a variety of causes, the development of the corpus callosum can be impaired - this brain malformation is known as corpus callosum dysgenesis (CCD). The clinical presentation of CCD varies, with patients exhibiting three morphological phenotypes: agenesis, partial dysgenesis, and hypoplasia. Although the first two presentations are easily detectable on MRI scans, the latter is more challenging, as the structure is fully formed but has a reduced area. In this study, we develop (1) a pipeline to generate synthetic MRI scans with apparent anatomical variation and (2) train a U-Net-based tool to automatically segment the corpus callosum of marmosets in both healthy and disease contexts. Methodologically, a custom script was devised to apply rotation and translation to T1-weighted MRI scans at the volume level. Because the slicing grid remains unchanged, these rigid transformations translate into apparent anatomical variations at the slice level. We compared corpus callosum measurements obtained from automatically segmented masks with those from manually delineated masks. The average Dice score was above 0.90, and the Hausdorff distance was below 0.4 mm. We also stratified our cohort according to phenotype (healthy controls and hypoplastic animals). The magnitude of the effect and the significance level observed between the voxel counts of healthy and hypoplastic animals using manually delineated masks were comparable to those obtained via automatic segmentations. These results show that our pipeline can generate a sufficiently varied training pool to build an accurate U-Net segmentation model with high diagnostic capability.

neuroscience↗

bioRxiv2025

Noninvasive focal gene transfer of chemogenetic proteins in the primate brain

The development of chemogenetic neuromodulators, including Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), have enabled focally specific, long-lasting, and reversible neuromodulation in the primate brain. Although systemically delivered synthetic ligands allow for noninvasive actuation of chemogenetic receptors, direct intraparenchymal injection remains atop the available methods to precisely deliver chemogenetic payloads to a specific target of the brain. The requirement of trephination, however, is accompanied by inherent risks of infection, long recovery times, and often tissue damage with concomitant behavioral complications. When considering therapeutic injections, the requirement of transcranial surgery does not translate well to the clinic, especially when repeated administrations are required. Here, we leverage our recent development of transcranial focused ultrasound (tFUS) for noninvasive and focal delivery of adeno-associated viruses (AAVs) carrying excitatory Gq-DREADDs to frontal cortical targets (areas 6DR and 8aD) in the marmoset brain. Using [18F]-fluorodeoxyglucose (FDG) positron emission tomography, we demonstrate significant increases in glucose metabolism at the site of viral delivery after administering the DREADD-specific agonist deschloroclozapine (DCZ), as compared to vehicle control. Focal neuronal DREADD expression was confirmed by immunohistochemistry at the site of opening. Through comparison of awake resting-state functional connectivity (whole brain connectivity with the sites of delivery) and structural connectivity (directly injected viral neuronal tracing at the sites of delivery) we demonstrate that the increase in glucose metabolism occurs at both mono- and polysynaptically connected brain regions. Taken together, these results demonstrate the ability to focally deliver excitatory chemogenetics without the need for surgery, allowing for activation of long-range frontal cortex circuits of the primate brain.

neuroscience↗

bioRxiv2023

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations. Significance statementBrain connectivity is a central topic in neuroscience. Understanding how brain areas can communicate allows for the comprehension of brain structure and function. We have described in rodents a new commissure pathway that connects the cortex to the contralateral thalamus. Here, we investigate whether this pathway exists in non-human primates and humans. The presence of these commissures poses the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

neuroscience↗

bioRxiv2020

Analysis of Hippocampal Subfields in Sickle Cell Disease Using Ultrahigh Field MRI

Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes organ dysfunction, including cerebral vasculopathy and neurological complications. Hippocampal segmentation with newer and advanced 7 Tesla (7T) MRI protocols has revealed atrophy in specific subregions in other neurodegenerative and neuroinflammatory diseases, however, there is limited evidence of hippocampal involvement in SCD. Thus, we explored whether SCD may be also associated with abnormalities in hippocampal subregions. We conducted 7T MRI imaging in individuals with SCD, including the HbSS, HbSC and HbS/beta thalassemia genotypes (n=37), and healthy race and age-matched controls (n=40), using a customized head coil. Both T1 and T2 weighted images were used for automatic segmentation of the hippocampus subfields. Individuals with SCD had significantly smaller volume of the Dentate Gyrus and Cornu Ammonis (CA) 2 and 3 as compared to the control group. Other hippocampal subregions also showed a trend towards smaller volumes in the SCD group. These findings support previous reports of reduced volume in the temporal lobe in SCD patients. Further studies are necessary to investigate the mechanisms that lead to structural changes in the hippocampus subfields and their relationship with cognitive performance in SCD patients.

neuroscience↗