Biology subjects

Mallela, A. N.

Publications and source records attributed to Mallela, A. N..

4 recordsLinked to original sources

bioRxiv2026

Stimulus-response correlation analysis dissociates spatiotemporal cortical networks supporting speech production

IntroductionUnderstanding the spatiotemporal distribution of cortical activation during language production is a central question in cognitive neuroscience with broad clinical applications. High spatial/temporal resolution recording over multiple brain regions and specific psycholinguistic manipulations with testable behavioral predictions are necessary to separate neural variance attributable to processing stages. ObjectiveWe combine a delayed naming paradigm with intracranial electrophysiology to identify spatiotemporally dissociated cortical networks supporting stages of speech production. MethodsSubjects (20 healthy, 15 intracranial electrophysiology) are presented visual stimuli to name but are instructed to delay response until a go cue at 0/400/1000ms. Exploiting the temporal variance induced by delay, we calculate stimulus/response-locked correlation of high gamma (70-200Hz) activity at each contact. We compare shifts in stimulus-response correlation space to response time (RT) to validate separation of networks. ResultsBehaviorally, the factor delay modulated the effect of lexical selection on RT (p=0.021) but did not modulate the effect of phonological planning (p=0.4), confirming the paradigm separates processing stages. Stimulus-response correlation analyses revealed globally-invariant structure across subjects. Certain regions showed strong stimulus-locking (occipital lobe) or response-locking (motor cortex), but most regions were intermediate. Shifts in correlation space identified dissociated networks that predicted substantial variance in RT from lexical selection (R2=0.64) and phonological density (R2=0.75). Using a leave-one-subject-out cross validation approach, these shifts explained 31.4% of variance in RT at the trial level. ConclusionStimulus-response correlation space reveals stable spatiotemporal signatures of psycholinguistic processing that generalize across individuals. This approach permits hyperalignment of neurophysiological data and functional separation of cortical networks in speech production across subjects.

neuroscience↗

bioRxiv2024

All-trans retinoic acid induces durable tumor immunity in IDH-mutant gliomas by rescuing transcriptional repression of the CRBP1-retinoic acid axis

Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes. Restorative retinoic acid therapy in murine glioma models promotes clonal CD4+ T cell expansion and induces tumor regression in IDHm, but not IDH wildtype (IDHwt), gliomas. Our findings provide a mechanistic rationale for RA immunotherapy in IDHm glioma and is the basis for an ongoing investigator-initiated, single-center clinical trial investigating all-trans retinoic acid (ATRA) in recurrent IDHm human subjects.

cancer biology↗

bioRxiv2022

Heterogeneous migration of neuronal progenitors to the insula shapes the human brain

The human cerebrum consists of a precise and stereotyped arrangement of lobes, gyri, and connectivity that underlies human cognition. The development of this arrangement is less clear. Current models of radial glial cell migration explain individual gyral formation but fail to explain the global configuration of the cerebral lobes. Moreover, the insula, buried in the depths of the Sylvian fissure, belies conventional models. Here, we show that the insula has unique morphology in adults, that insular morphology and slow volumetric growth emerge during fetal development, and that a novel theory of curved migration is required to explain these findings. We calculated morphologic data in the insula and other lobes in adults (N=107) and in an in utero fetal brain atlas (N=81 healthy fetuses). In utero, the insula grows an order of magnitude slower than the other lobes and demonstrates shallower sulci, less curvature, and less surface complexity both in adults and progressively throughout fetal development. Novel spherical projection analysis demonstrates that the lenticular nuclei obstruct 60-70% of radial pathways from the ventricular zone (VZ) to the insula, forcing a curved migration path to the insula in contrast to a direct radial pathway. Using fetal diffusion tractography, we identify streams of putative progenitor cells that originate from the VZ and migrate tangentially around the lenticular nuclei to form the insula. These results challenge existing models of radial migration to the cortex, provide an alternative model for insular and cerebral development, and lay the groundwork to understand cerebral malformations, insular functional connectivity, and insular pathologies.

developmental biology↗

bioRxiv2019

Different principles govern different scales of brain folding

The signature folds of the human brain are formed through a complex and developmentally regulated process. In vitro and in silico models of this process demonstrate a random pattern of sulci and gyri, unlike the highly ordered and conserved structure seen in the human cortex. Here, we account for the large-scale pattern of cortical folding by combining advanced fetal MRI with nonlinear diffeomorphic registration and volumetric analysis. Our analysis demonstrates that in utero brain growth follows a logistic curve, in the absence of an external volume constraint. The Sylvian fissure forms from interlobar folding, where separate lobes overgrow and close an existing subarachnoid space. In contrast, other large sulci, which are the ones represented in existing models, fold through an invagination of a flat surface, a mechanistically different process. Cortical folding is driven by multiple spatially and temporally different mechanisms, therefore regionally distinct biological process may be responsible for the global geometry of the adult brain.

neuroscience↗