Biology subjects

Tandon, N.

Publications and source records attributed to Tandon, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Microelectrode arrays enable directional stereo-EEG during kainate-mediated seizures

Surgical planning for drug-resistant epilepsy often relies on stereo-EEG (sEEG) recordings obtained with cylindrical ring electrodes. Prior modeling studies, including lead-field analysis, suggest that microelectrodes distributed around an sEEG-sized insulating body offer superior source amplification and directional sensitivity that are not available with either a ring design or microelectrodes on micro-structures, e.g. Neuropixel. However, these advantages have not been demonstrated in seizure models. This study evaluated high-density sEEG recordings using directional microelectrode arrays in a kainate-mediated rat model (n=6). Two 64-channel microelectrode arrays were implanted near the hippocampus, and the signals were spatially averaged to emulate virtual ring electrodes for comparison. Device locations were reconstructed and placed in copies of the Waxholm Space Rat Brain Atlas registered to subject-specific MRI scans. In subjects exhibiting seizures (n=4), automated line length detection showed that microelectrode signals identified epileptiform activity sooner and with greater specificity than ring electrodes. In subjects that only seized post-kainate injection (n=3), manual review by a board-certified epileptologist confirmed that microelectrodes provided the earliest onset detection times. Furthermore, the microelectrode arrays high resolution revealed distinct instances of hyperactivity occurring at similar depths but from different directions -- a feature indistinguishable to standard ring electrodes. These results demonstrate that microelectrodes on a large insulating body significantly enhance signal quality and spatial localization. This technology offers a potential advancement over current clinical standards for identifying seizure foci during surgical planning. SIGNIFICANCESurgical treatment for drug-resistant epilepsy depends on accurately identifying the brain regions where seizures begin. Current stereo-EEG electrodes sample activity with ring contacts that average signals around the probe shaft, potentially obscuring directional differences in nearby neural activity. This study shows that microelectrodes distributed around an sEEG-sized insulating body can improve seizure-related signal detection and spatial localization compared with ring-like recordings from the same implant locations. By resolving activity that conventional ring electrodes cannot distinguish, high-density directional sEEG may provide more informative recordings for seizure mapping. These findings support the development of next-generation intracranial electrodes for improving epilepsy surgical planning.

neuroscience↗

bioRxiv2026

STING suppresses migration of murine triple-negative breast cancer cells E0771 and 4T1 in vitro

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and lacks effective therapies. The stimulator of interferon genes (STING) has been shown to both suppress and promote migration in various cancer types, but its role in TNBC remains unclear. To investigate this, we established STING-overexpressing murine TNBC cell lines and assessed their migratory and proliferative behavior. STING overexpression significantly suppressed cell migration without affecting cell proliferation. Furthermore, STING overexpression in E0771 cells upregulated expression levels of Itgb1 and Itga6 significantly, but not Icam1, Cxcl3, Itgb2, Lama5, or Rhoa. These findings highlight the potential anti-migratory role of STING beyond immunomodulatory functions.

cancer biology↗

bioRxiv2025

The Rab32 small GTPase is required for efficient cross-priming of CD8+ T cellsagainst cell-associated antigens by XCR1+ type 1 DCs in vivo.

Type 1 conventional dendritic cells (cDC1s) are critical for initiating adaptive immune responses through the cross-priming of CD8 T cells against antigens from tumor or virus-infected cells. This function depends on specialized cross-presentation pathways that allow cDC1s to process phagocytosed cell debris and present peptide-MHC I complexes. In this study, we identify the small GTPase Rab32 as being highly and selectively over-expressed in cDC1s as compared to cDC2s. While cDC1s from Rab32-deficient mice develop normally and can respond to maturation signals, their capacity to activate CD8 T cells in vivo is impaired. Notably, Rab32- deficient cDC1s retain the ability to stimulate TCR transgenic CD8 T cells ex vivo using both cell-associated antigens and MHC I-binding peptides of varying affinity. However, in vivo, Rab32 is essential for effective CD8 T cell responses to cell-associated antigens, independent of Rab32 expression in T cells themselves. Importantly, Rab32-mediated cross-priming is required for the efficient expansion of tumor-specific CD8 T cells into solid tumors. These findings underscore a critical role for Rab32 in cDC1-mediated cross-priming, highlighting the contribution of non-antigen processing vesicular pathways in shaping CD8 T cell responses to cellular antigens.

immunology↗

bioRxiv2025

Optimizing electrode placement and information capacity for local field potentials in cortex

Recent neurosurgery advancements include improved stereotactic targeting and increased density and specificity of electrophysiological evaluation. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. One key tool is a genetic algorithm that optimizes electrode placement by maximizing information capacity. Another is a sparse sensor method, Sparse Electrode Placement for Input Optimization (SEPIO), that selects the best sensor subsets for accurate source classification. We demonstrate several use cases for clinicians, engineers, and researchers. Overall, these open-source tools provide a quantitative framework to select devices from a neurosurgical armament and to optimize device and contact placement. Using these tools may help refine electrode coverage with low channel count devices while minimizing the burden of invasive surgery. The study demonstrates that optimized electrode placement significantly improves the information capacity and signal quality of local field potential (LFP) recordings. The tools developed offer a valuable approach for refining neurosurgical techniques and enhancing the design of neural implants. HighlightsO_LItool for simulating subject-specific local field potentials and electrode sensitivity. C_LIO_LIptimized electrode placement enhances ROI source coverage, and signal quality. C_LIO_LIsensor-based classification boosts data quality without extra electrode cost. C_LIO_LIcomparisons of devices and contact arrangements. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/650658v3_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1a3a7aaorg.highwire.dtl.DTLVardef@154a776org.highwire.dtl.DTLVardef@be4826org.highwire.dtl.DTLVardef@72caa9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Targeting tGLI1, a novel mediator of tumor therapeutic resistance, using Ketoconazole sensitizes glioblastoma to CDK4/6 therapy and Chemoradiation

Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with no effective treatments. While cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) show clinical promise in some cancers, they have not significantly improved survival in GBM patients. This lack of response is attributed to the treatment-resistant glioma stem cell (GSC) population. We previously identified truncated glioma-associated oncogene homolog 1 (tGLI1) as a novel transcription factor promoting GSCs; however, its role in CDK4/6i resistance has never been investigated in any cancer type. Here, we found positive correlations between tGLI1 and CDK4/6 therapeutic resistance in patient datasets and in vitro studies. Pharmacological inhibition of tGLI1 using FDA-approved ketoconazole (KCZ), a tGLI1-specific inhibitor, sensitized GBM and GSCs to CDK4/6is. KCZ+CDK4/6i combination therapy demonstrated synergistic anti-proliferative effects, significantly inhibiting GBM stemness and cell cycle progression while increasing apoptosis. The combination was more efficacious than monotherapies in two orthotopic GBM mouse models. tGLI1 promoted GBM resistance to radiation therapy and temozolomide, while KCZ potentiated effects of these treatments. Collectively, we report for the first time that tGLI1 is a novel mediator of GBM resistance to CDK4/6is, and KCZ sensitizes GBM to CDK4/6is, thereby supporting future clinical utility of novel KCZ+CDK4/6i combinatorial therapy for GBM patients.

cancer biology↗

bioRxiv2024

Small-molecule-based regulation of gene expression in human astrocytes upon both positive and negative actuations of G-quadruplex control systems

A great deal of attention is currently being paid to strategies aiming at uncovering the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells using G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved through the implementation of a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived human brain cells. Our results show that the stabilization of G4s by PDS triggers the dysregulation of many cellular circuitries, the most drastic effects originating in the downregulation of 354 transcripts and 158 proteins primarily involved in RNA transactions. In contrast, the destabilization of G4s by PhpC modulates the G4 landscapes in a far more focused manner with the upregulation of 295 proteins mostly involved in RNA transactions as well, thus mirroring the effects of PDS. Our study is the first of its kind to report on the extent of G4-associated cellular circuitries in human cells by systematically pitting the effect of G4 stabilization against destabilization in a direct and unbiased manner.

genetics↗

bioRxiv2023

Supplementary motor area in speech initiation: a large-scale intracranial EEG evaluation of stereotyped word articulation

Speech production is known to engage a distributed network. The brain regions responsible for the initiation of articulation are unclear, and they would be expected to coordinate a distributed network. Using direct intracranial recordings in a large cohort, during stereotyped speech production to eliminate confounds of phonological and semantic complexity, we performed a comprehensive analysis of cortical sites engaged in speech initiation. We found that the supplementary motor area (SMA) was the earliest speech motor region to be active prior to speech onset and was active almost exclusively prior to articulation. Broadband gamma activity in the SMA was predictive of the response time of word production, predicting response time from 250 ms after stimulus onset. Neural activity in SMA began at a highly predictable time after stimulus onset and extended until speech onset. SMA activity offset coincided with ventral premotor cortex and primary motor activity onset. This suggests that the SMA may coordinate the concerted activation of motor execution cortex. Our results support the idea that SMA is a key node in the speech initiation network. Significance statementProducing speech requires coordination across multiple brain regions. One cortical region - the supplementary motor area (SMA) - has long been a candidate region to coordinate across other regions to initiate speech production. In this study, we used human intracranial recordings from patients with epilepsy to investigate the role of the SMA in initiating speech. In a picture-naming task, subjects repeated the word "scrambled" scores of times; using this condition to eliminate any linguistic confounds, we found that the SMA was consistently one of the earliest regions to activate during word production. We also uncovered the SMAs temporally precise tuning to speech onset at the single-trial level.

neuroscience↗

bioRxiv2022

Epigenetic and Signaling Determinants of Blood-Brain Barrier-Regulatory Genetic Networks

The blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulators histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/{beta}-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.

neuroscience↗

bioRxiv2022

The spatiotemporal dynamics of semantic integration in the human brain

Language depends critically on the integration of lexical information to derive semantic concepts. The neurobiology of this fundamental aspect of human cognition remains mostly unknown. Limitations of spatiotemporal resolution have previously rendered it difficult to disentangle processes involved in semantic integration from independent computations such as tracking word meaning and establishing referents. We utilized intracranial recordings (n = 58) during the presentation of orthographic descriptions that were either referential or non-referential to a common object. Referential contexts enabled high frequency broadband gamma activation (70-150 Hz) of a distributed network including the inferior frontal sulcus (IFS), medial parietal cortex (MPC) and medial temporal lobe (MTL) in the left, language-dominant hemisphere. Components of this network (IFS, MPC), alongside posterior superior temporal sulcus, showed greater engagement for trials that did not progressively isolate a limited set of referents, relative to trials that did. IFS and posterior middle temporal gyrus activity was modulated by semantic coherence, regardless of whether the sentence picked out a common object. Centered around IFS and spreading out dorsally towards middle frontal gyrus and ventrally towards anterior/posterior inferior frontal gyrus, we uncovered a cortical mosaic of functional specialization for reference, coherence and semantic narrowing. Early processing windows implicated IFS in all aspects of semantics, and in later windows sub-portions of IFS exposed a clearer functional tessellation with some remaining overlap. This work unveils how lateral fronto-temporal regions make distinctly rich semantic contributions and are involved jointly in semantic integration and conflict resolution, depending on the sub-region and processing stage.

neuroscience↗

bioRxiv2021

The critical role of the ventral temporal lobe in word retrieval

Deficits in word retrieval are a hallmark of a variety of neurological illnesses spanning from dementia to traumatic injuries. The role of the dominant temporal lobe in fluent naming has been characterized by lesional analyses, functional imaging, and intracranial recordings, but limitations of each of these measures preclude a clear assessment of which specific constituent of the temporal lobe is critical for naming. We studied a large cohort of patients undergoing surgical resections or laser ablations of the dominant temporal lobe for medically intractable epilepsy (n=95). These techniques are exceedingly effective for seizure control but often result in language declines, particularly in confrontation naming, which can be socio-economically disabling. We used a multivariate voxel-based lesion symptom mapping analysis to localize brain regions significantly associated with visual object naming deficits. We observed that posterior inferior temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in confrontation naming. Furthermore, we found that the posterior margin of anterior temporal lobectomies was linearly correlated to a decline in visual naming with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe. We integrated these findings with electrocorticography during naming in a subset of this population and found that the majority of cortical regions whose resection was associated with a significant decline overlapped with regions that were functionally most active prior to articulation. Importantly, these loci coincide with the sites of susceptibility artifacts during echo-planar imaging, which explains why this region has not previously been implicated. Taken together, these data highlight the crucial contribution of the posterior ventral temporal cortex in lexical access and its important role in the pathophysiology of anomia following temporal lobe resections. Surgical strategies, including the use of laser ablation to target the medial temporal lobe as well as microsurgical approaches, should attempt to preserve this region to mitigate postoperative language deficits.

neuroscience↗

bioRxiv2021

The Listening Zone of Human Electrocorticographic Field Potential Recordings

Intracranial electroencephalographic (icEEG) recordings provide invaluable insights into neural dynamics in humans due to their unmatched spatiotemporal resolution. Yet, such recordings reflect the combined activity of multiple underlying generators, confounding the ability to resolve spatially distinct neural sources. To empirically quantify the listening zone of icEEG recordings, we computed the correlations between signals as a function of distance (expressed as full width at half maximum; FWHM) between 8,752 recording sites in 71 patients implanted with either subdural electrodes (SDE), stereo-encephalography electrodes (sEEG), or high-density sEEG electrodes. As expected, for both SDE and sEEG electrodes, higher frequency signals exhibited a sharper fall off relative to lower frequency signals. For broadband high gamma (BHG) activity, the mean FWHM of SDEs (6.6 {+/-} 2.5 mm) and sEEGs in gray matter (7.14 {+/-} 1.7 mm) was not significantly different, however the FWHM for low frequencies recorded by sEEGs was 2.45 mm smaller than SDEs. White matter sEEG electrodes showed much lower power for frequencies 17 to 200 Hz (q < 0.01) and a much broader decay (11.3 {+/-} 3.2 mm) than gray matter electrodes (7.14 {+/-} 1.7 mm). The use of a bipolar referencing scheme significantly lowered FWHM for sEEG electrodes, as compared with a white matter reference or a common average reference. These results outline the influence of array design, spectral bands, and referencing schema on local field potential recordings and source localization in icEEG recordings in humans. The metrics we derive have immediate relevance to the analysis and interpretation of both cognitive and epileptic data.

neuroscience↗

bioRxiv2021

Sensing Local Field Potentials with a Directional and Scalable Depth Array: DISC

A variety of electrophysiology tools are available to the neurosurgeon for diagnosis, functional therapy, and neural prosthetics. However, no tool can currently address these three critical needs: (i) access to all cortical regions in a minimally invasive manner; (ii) recordings with microscale, mesoscale, and macroscale resolutions simultaneously; and (iii) access to spatially distant multiple brain regions that constitute distributed cognitive networks. We present a novel device for recording local field potentials (LFPs) with the form factor of a stereo-electroencephalographic electrode but combined with radially positioned microelectrodes and using the lead body to shield LFP sources, enabling directional sensitivity and scalability, referred to as the DISC array. As predicted by our electro-quasistatic models, DISC demonstrated significantly improved signal-to-noise ratio, directional sensitivity, and decoding accuracy from rat barrel cortex recordings during whisker stimulation. Critically, DISC demonstrated equivalent fidelity to conventional electrodes at the macroscale and uniquely, revealed stereoscopic information about current source density. Directional sensitivity of LFPs may significantly improve brain-computer interfaces and many diagnostic procedures, including epilepsy foci detection and deep brain targeting.

bioengineering↗

bioRxiv2021

Event-Related Phase Synchronization Propagates Rapidly across Human VentralVisual Cortex

Visual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression following both stimulus onset and offset, consistent across trials and tasks. The phase of low frequency activity in anterior regions was predicted by the prior phase in posterior cortical regions. This spatiotemporal propagation of phase likely serves as a feed-forward organizational influence enabling the integration of information across the ventral visual stream. This phase modulation manifests as the early components of the event related potential; one of the most commonly used measures in human electrophysiology. These findings illuminate fundamental organizational principles of the higher order visual system that enable the rapid recognition and characterization of a variety of inputs.

neuroscience↗

bioRxiv2021

Network analysis after epigenome-wide methylation study revealed JUP as a regulator of co-methylated risk-module for T2DM

Controlling the global Type 2 diabetes mellitus (T2DM) pandemic requires a better understanding of its risk factors across different populations, and needs markers that can precisely predict the individual risk to the disease. DNA methylation due to environmental factors is a known mechanism for conferring risk to T2DM. To identify such methylation signatures and associated risk to the disease, we performed an epigenome-wide-association study (EWAS) in 844 individuals of Indo-European origin. Within the Indian population, we identified and validated 6 novel differentially methylated CpG sites in PDCD6IP, MIR1287, 5S_rRNA, HDAC9, KCNK16, and RTN1 genes associated with T2DM risk at the epigenome-wide-significance-level (p<1.2x10-7). Further, we also replicated the association of 3 known CpG sites in TXNIP, SREBF1 and CPT1A in the Indian population. Using methylation-based-network analysis, we identified 4 co-methylated modules, which we named as turquoise, yellow, brown, and blue, among differentially methylated CpG sites in discovery phase samples. We observed that methylation of the brown module with 28 CpG sites, associated with T2DM risk factors (e.g., BMI, insulin, C-peptide). Upon further analysis, we noted that these methylation signatures at 14 of the brown modules CpG can be used as marker to segregate T2DM patients with good glycemic control (e.g., low HbA1c) but poor lipid profile (low HDL and high TG) from the other patients. Additionally, we discovered that rs6503650 in the JUP gene regulates methylation at all the 14 hub CpG sites of the brown modules as methQTL. Our network-assisted epigenome-wide association study is the first to systematically explore DNA methylations conferring risks to T2DM. In addition, the study shows the potential use of identified risk CpG sites for patient segregation with different clinical outcomes. These findings can be useful for better stratification of patient in order to improve the clinical management and treatment outcomes.

genomics↗

bioRxiv2021

A Spatiotemporal Map of Reading Aloud

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband gamma activity varies with multiple word attributes critical to reading speed: lexicality, word frequency and orthographic neighborhood. We found that lexicality is encoded earliest in mid-fusiform (mFus) cortex and precentral sulcus, and is represented reliably enough to allow single-trial lexicality decoding. Word frequency is first represented in mFus and later in the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS), while orthographic neighborhood sensitivity resides solely in IPS. We thus isolate the neural correlates of the distributed reading network involving mFus, IFG, IPS, precentral sulcus and motor cortex and provide direct evidence for dual-route models of reading, with parallel processes via the lexical route from mFus to IFG, and the sub-lexical route from IPS and precentral sulcus to anterior IFG.

neuroscience↗

bioRxiv2021

Minimal phrase composition revealed by intracranial recordings

The ability to comprehend phrases is an essential integrative property of the brain. Here we evaluate the neural processes that enable the transition from single word processing to a minimal compositional scheme. Previous research has reported conflicting timing effects of composition, and disagreement persists with respect to inferior frontal and posterior temporal contributions. To address these issues, 19 patients (10 male, 19 female) implanted with penetrating depth or surface subdural intracranial electrodes heard auditory recordings of adjective-noun, pseudoword-noun and adjective-pseudoword phrases and judged whether the phrase matched a picture. Stimulus-dependent alterations in broadband gamma activity, low frequency power and phase-locking values across the language-dominant left hemisphere were derived. This revealed a mosaic located in the posterior superior temporal sulcus (pSTS), in which closely neighboring cortical sites displayed exclusive sensitivity to either lexicality or phrase structure, but not both. Distinct timings were found for effects of phrase composition (210-300 ms) and pseudoword processing (approximately 300-700 ms), and these were localized to neighboring electrodes in pSTS. The pars triangularis and temporal pole encode anticipation of composition in broadband low frequencies, and both regions exhibit greater functional connectivity with pSTS during phrase composition. Our results suggest that the pSTS is a highly specialized region comprised of sparsely interwoven heterogeneous constituents that encodes both lower and higher level linguistic features. This hub in pSTS for minimal phrase processing may form the neural basis for the human-specific computational capacity for forming hierarchically organized linguistic structures. SignificanceLinguists have claimed that the integration of multiple words into a phrase demands a computational procedure distinct from single word processing. Here, we provide intracranial recordings from a large patient cohort, with high spatiotemporal resolution, to track the cortical dynamics of phrase composition. Epileptic patients volunteered to participate in a task in which they listened to phrases ("red boat"), word-pseudoword or pseudoword-word pairs (e.g., "red fulg"). At the onset of the second word in phrases, greater broadband high gamma activity was found in posterior superior temporal sulcus in electrodes that exclusively indexed phrasal meaning, and not lexical meaning. These results provide direct, high-resolution signatures of minimal phrase composition in humans, a potentially species-specific computational capacity.

neuroscience↗

bioRxiv2021

What The Brain Does As We Speak

AO_SCPLOWBSTRACTC_SCPLOWLanguage is a defining human behavior and is dependent on networks interactions amongst broadly distributed neuronal substrates. Transient dynamics between language regions that underpin speech production have long been postulated, yet have proven challenging to evaluate empirically. We used direct intracranial recordings during single word production to create a finely resolved spatiotemporal atlas (134 patients, 25810 electrodes, 40278 words) of the entire language-dominant cortex and used this to derive single-trial state-space sequences of network motifs. We derived 5 discrete neural states during the production of each word, distinguished by unique patterns of distributed cortical interaction. This interactive model was significantly better than a model of the same design but lacking interactions between regions in explaining observed activity. Our results eschew strict functional attribution to localized cortical populations, supporting instead the idea that cognitive processes are better explained by distributed metastable network states.

neuroscience↗

bioRxiv2020

Spatiotemporal Dynamics of Orthographic and Lexical Processing in the Ventral Visual Pathway

Reading is a rapid, distributed process that engages multiple components of the ventral visual stream. However, the neural constituents and their interactions that allow us to identify written words are not well understood. Using direct intracranial recordings in a large cohort of humans, we comprehensively isolated the spatiotemporal dynamics of visual word recognition across the entire left ventral occipitotemporal cortex. The mid-fusiform cortex is the first region that is sensitive to word identity and to both sub-lexical and lexical frequencies. Its activation, response latency and amplitude, are highly dependent on the statistics of natural language. Information about lexicality and word frequency propagates posteriorly from this region to traditional visual word form regions and to earlier visual cortex. This unique sensitivity of mid-fusiform cortex to the lexical characteristics of written words points to its central role as an orthographic lexicon, which accesses the long-term memory representations of visual word forms.

neuroscience↗