Biology subjects

Cajigas, I.

Publications and source records attributed to Cajigas, I..

8 recordsLinked to original sources

bioRxiv2026

Toward A Whole-Brain Interface Enabled by High-Resolution Surface Electrophysiology

The goal of building a whole-brain interface - capable of generating a real-time digital representation of the state of the entire central nervous system - has long been framed as a hardware challenge of recording simultaneously from ever-larger numbers of microelectrodes. Advances in high-resolution neural interfaces now enable electrophysiologic interaction with the human nervous system at spatial and temporal resolutions previously unattainable without disrupting tissue architecture or physiology. These capabilities create new opportunities for mechanistic neuroscience, neuroprosthetics, and precision-guided neurosurgery. With the advent of modern microelectrode array technology, however, the whole-brain interface has also become a data challenge. Rather than pursuing large-scale human brain recording purely through a single device placed in a single patient, we demonstrate here that systematic multi-subject aggregation, across brain regions and behavioral paradigms, in a common anatomical framework, can achieve something functionally similar to a whole-brain interface. Here we present an approach to a functional atlas of the human central nervous system derived from high-resolution surface electrophysiology recordings obtained in the first 70 patients implanted with an anatomically conformal, thin-film neural interface positioned in more than 100 locations. The atlas comprises >100,000 electrode deployments and catalogs placement across a broad range of neuroanatomic targets spanning the motor, sensory, language, auditory, and associative domains, as well as brainstem and spinal cord structures that have historically been difficult to access at high electrophysiologic resolution. Across participants, aggregated recordings reveal somatotopic organization, including digit representations that follow a lateral-to-medial ordering consistent with classical homuncular maps, with transitions between adjacent representations occurring over spatial scales of approximately 0.8 - 2.0 mm; canonical frequency-band signatures, such as movement-related beta-band suppression and focal high-gamma (70 - 200 Hz) increases during motor and speech behaviors; and task-modulated population dynamics in both evoked and spontaneous activity across cortical, brainstem, and spinal cord regions. These findings yield insight into patterns of mesoscale electrophysiological dynamics conserved across the entire human central nervous system, suggesting that fine-scale functional organization is preserved across individuals when aligned to common anatomical landmarks. We further demonstrate several applications of these high-resolution recordings, including real-time neural decoding from upper extremity motor cortex to enable real-time neuroprosthetic control, and from ventrolateral cortex to decode cortical correlates of spoken language, facial movements, and complex facial expressions of emotion, supporting initial feasibility of combined verbal and nonverbal communication interfaces. Together, these results establish a paradigm for approaching large-scale interfaces with the human brain, as well as a starting point for a scalable, extensible atlas of human electrophysiologic function designed to accelerate discovery across basic neuroscience, translational research, and clinical neurotechnology.

neuroscience↗

bioRxiv2024

Return of intracranial beta oscillations and traveling waves with recovery from traumatic brain injury

Traumatic brain injury (TBI) remains a pervasive clinical problem associated with significant morbidity and mortality. However, TBI remains clinically and biophysically ill-defined, and prognosis remains difficult even with the standardization of clinical guidelines and advent of multimodality monitoring. Here we leverage a unique data set from TBI patients implanted with either intracranial strip electrodes during craniotomy or quad-lumen intracranial bolts with depth electrodes as part of routine clinical practice. By extracting spectral profiles of this data, we found that the presence of narrow-band oscillatory activity in the beta band (12-30 Hz) closely corresponds with the neurological exam as quantified with the standard Glasgow Coma Scale (GCS). Further, beta oscillations were distributed over the cortical surface as traveling waves, and the evolution of these waves corresponded to recovery from coma, consistent with the putative role of waves in perception and cognitive activity. We consequently propose that beta oscillations and traveling waves are potential biomarkers of recovery from TBI. In a broader sense, our findings suggest that emergence from coma results from recovery of thalamo-cortical interactions that coordinate cortical beta rhythms.

neuroscience↗

bioRxiv2024

Cellular heterogeneity in the developing forebrain masks transcriptional outcomes and principles of Evf2 enhancer lncRNA-Dlx5/6UCE-gene guidance

During mouse embryonic brain development, the Evf2 ultraconserved enhancer (UCE) lncRNA guides the Dlx5/6UCE to [~]129 sites across chr6. However, previous work identified only 4 transcriptionally regulated targets associated with Evf2-Dlx5/6UCE enhancer-gene guided sites (EGGs), raising questions about the significance of the majority of Evf2-EGGs. Here, single cell transcriptomics (scRNAseq) shows that Evf2-EGGs on chr6 coincide with subpopulation-specific Evf2 transcriptional targets, revealing far greater alignment between EGGs and transcriptional targets than previously reported. Surprisingly, subpopulation-specific Evf2 regulated gene networks in embryonic progenitors predict adult synaptic and seizure defects. Evf2 regulation of EGGs to gene bodies (GB, Dlx5/6UCE locations within {+/-}5kb of the target gene) divides chr6 into short-range (<10Mb distant), highly activated genes, and long/super-long-range (10-129Mb), moderately repressed genes. Clustering of Evf2 transcriptionally regulated chr6 targets in populations where Evf2 is first activated supports that Evf2-EGG transcriptional effects can occur from EGG shifts as far as 3Mb, uncoupling enhancer shift distance and transcriptional direction from transcriptional outcome. Evf2 RNA binding sites (RBSs) divide chr6 into 4 major regions, consistent with a role for RBS chromosomal spacing in long-and super-long-range EGG selectivity. Surprisingly, 95% of 147 RBSs genome-wide potentially form inter-chromosomal DNA loops. Evf2-regulated combinatorial recruitment of Evf2-ribonucleoproteins at EGGs and RBSs, together with effects on homeodomain transcription factor DNA motif recognition, support a novel model of lncRNA directed multi-modal EGG selectivity during intra- and inter-chromosomal gene regulation.

molecular biology↗

bioRxiv2022

Subsensory stochastic electrical stimulation targeting muscle afferents alters gait control during locomotor adaptations to haptic perturbations

Subsensory noise stimulation targeting sensory receptors has been shown to improve balance control in healthy and impaired individuals. However, the potential for application of this technique in other contexts is still unknown. Gait control and adaptation rely heavily on the input from proprioceptive organs in the muscles and joints. Here we investigated the use of subsensory noise stimulation as a means to influence motor control by "boosting" proprioception during locomotor adaptations to forces delivered by a robot. The forces increase step length unilaterally and trigger an adaptive response that restores the original symmetry. Healthy participants performed two adaptation experiments, one with stimulation applied to the hamstring muscles and one without. We found that participants adapted faster but to a lesser extent when undergoing subsensory stimulation. We argue that this behaviour is due to the dual effect that the stimulation has on the afferents encoding position and velocity that are present in the muscle spindles.

neuroscience↗

bioRxiv2021

Source-sink connectivity: a novel resting-state EEG marker of the epileptogenic zone

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy (DRE). Successful surgery is a standard of care treatment for DRE but can only be achieved through complete resection or disconnection of the epileptogenic zone (EZ), the brain region(s) where seizures originate. Surgical success rates vary between 20-80% because no clinically validated biological markers of the EZ exist. Localizing the EZ is a costly and time-consuming process beginning with non-invasive neuroimaging and often followed by days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity (e.g., low-voltage high frequency activity) on individual channels occurring immediately before seizures or spikes that occur on interictal iEEG (i.e., between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in EZ localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. Intracranial EEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aim to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the EZ. We hypothesize that when a patient is not clinically seizing, it is because the EZ is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighboring nodes ("sources") and the inhibited nodes themselves ("sinks"). Specifically, patient-specific dynamical network models (DNMs) were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics (SSMs). We validated the SSMs in a retrospective analysis of 65 patients by using the SSMs of the annotated EZ to predict surgical outcomes. The SSMs predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians predictions (surgical success rate of this dataset). In failed outcomes, we identified regions of the brain with high SSMs that were untreated. When compared to high frequency oscillations, the most commonly proposed interictal iEEG feature for EZ localization, SSMs outperformed in predictive power (by a factor of 1.2) suggesting SSMs may be an interictal iEEG fingerprint of the EZ.

bioengineering↗

bioRxiv2020

Sox2-RNA mechanisms of chromosome topological control in developing forebrain

Precise regulation of gene expression networks requires the selective targeting of DNA enhancers. The Evf2 long non-coding RNA regulates Dlx5/6 ultraconserved enhancer(UCE) interactions with long-range target genes, controlling gene expression over a 27Mb region in mouse developing forebrain. Here, we show that Evf2 long range gene repression occurs through multi-step mechanisms involving the transcription factor Sox2, a component of the Evf2 ribonucleoprotein complex (RNP). Evf2 directly interacts with Sox2, antagonizing Sox2-dependent Dlx5/6UCE activation. Evf2 regulates Sox2 binding at key sites, including the Dlx5/6eii shadow enhancer and Dlx5/6UCE interaction sites. Evf2 differentially targets RNP-associated Sox2 protein pools (PPs), redirecting Sox2-PPs to one repressed gene at the expense of the other. Co-regulation of Dlx5/6UCEintrachromosomal interactions by Evf2 and Sox2 reveals a role for Sox2 in chromosome topology. We propose that RNA organizes RNPs in a subnuclear domain, regulating both long-range UCE targeting and activity through Sox2-RNP sequestration and recruitment.

molecular biology↗

bioRxiv2019

Nodal Fragility of Intracranial EEG Networks: Towards an EEG Fingerprint for the Epileptogenic Zone

Over 15 million epilepsy patients worldwide do not respond to drugs. Successful surgical treatment requires complete removal, or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new EEG marker - neural fragility - in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43/47 surgical failures with an overall prediction accuracy of 76%, compared to the accuracy of clinicians being 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability suggesting neural fragility as an EEG biomarker of the SOZ.

neuroscience↗

bioRxiv2017

Poly(A) Binding Protein Nuclear 1 regulates the polyadenylation of key synaptic plasticity genes and plays a role in homeostatic plasticity

Polyadenylation is a nuclear process that involves the endonucleolytic cleavage of RNA transcripts and the addition of poly(A) tails. The cleavage often takes place at different positions within the same RNA transcript, generating alternative 3ends. Polyadenylation regulates mRNA localization, stability and translation and is likely to regulate complex processes such as synapse formation, synaptic plasticity and memory. Here we examined whether PolyA Binding Protein Nuclear 1 (Pabpn1), an RNA binding protein known to regulate alternative polyadenylation and polyA tail length in other systems, regulates neuronal mRNA function. Using immunocytochemistry we determined that Pabpn1 is present in both hippocampal slices and cultured hippocampal neurons. Applying shRNAs to knock-down Pabpn1 we discovered that Pabpn1 regulates the mRNA abundance and localization of key synaptic plasticity genes including Calcium/Calmodulin Dependent Protein Kinase II Alpha (Camk2a) and Glutamate Ionotropic Receptor AMPA Type Subunit 2 (Gria2). Furthermore, Pabpn1 knock-down prevented the homeostatic scaling of synaptic transmission elicited by bicuculline. These data demonstrate a link between Pabpn1, polyadenylation and neuronal plasticity.

neuroscience↗