Biology subjects

Garimella, A.

Publications and source records attributed to Garimella, A..

3 recordsLinked to original sources

bioRxiv2026

A Brain Circuit for Status Epilepticus

Status epilepticus (SE) is a life-threatening persistent epileptic seizure that can arise from various brain structures, leaving its brain circuit unknown. In this study, we utilize brain imaging changes during SE to reveal the brain architecture and circuit of persistent seizures. Multimodal lesion mapping identified that brain imaging changes during SE localize to a specific predisposed brain architecture characterized by increased metabolic rate, high synaptic and mitochondrial density, glutamate (mGLUR5 and NMDA) and GABA receptors. Gene expression patterns within lesion locations revealed a transcriptomic profile enriched for epilepsy pathologies (including SE), neuronal and synaptic processes, and glutamate signaling. Lesion network mapping demonstrated these same lesions map to a common brain circuit, unifying a traditionally heterogeneous patient population. Findings were validated in an independent cohort and the identified SE circuit distinguished brain imaging changes during SE from other lesion etiologies with excellent accuracy (91%), significantly outperforming all other tested maps. With this SE circuit, we identify therapeutic targets for precision therapy that could modulate this circuit. This study demonstrates brain imaging changes in SE converge on a unified brain circuit that could help diagnostic workup of patients in critical care and guide clinical trials of precision therapy for persistent seizures.

neuroscience↗

bioRxiv2026

A precise atlas of the human subcortex

Clinical interventions and neuroimaging in the subcortex require anatomical definitions that exceed the resolution and anatomical detail of currently available deformable brain atlases. Here, we introduce a high-resolution human brain atlas comprising 95 manually segmented grey and white matter structures as well as 82 white matter tracts compiled from a multitude of resources including ex-vivo MRI, histology, fibre dissections, and neuroanatomy textbooks. The atlas is defined at an isotropic resolution of 100 m and can be precisely deformed to individual subject brain anatomy. By providing precise definitions of both grey and white matter structures within and around the basal ganglia, thalamus, subthalamus, midbrain and cerebellum, the atlas provides a foundational resource for stereotactic surgery and subcortical brain imaging research, as well as for development of next-generation neuromodulation strategies.

neuroscience↗

bioRxiv2024

On the analysis of functional PET (fPET)-FDG: baseline mischaracterization can introduce artifactual metabolic (de)activations

Functional Positron Emission Tomography (fPET) with (bolus plus) constant infusion of [18F]-fluorodeoxyglucose FDG), known as fPET-FDG, is a recently introduced technique in human neuroimaging, enabling the detection of dynamic glucose metabolism changes within a single scan. However, the statistical analysis of fPET-FDG data remains challenging because its signal and noise characteristics differ from both classic bolus-administration FDG PET and from functional Magnetic Resonance Imaging (fMRI), which together compose the primary sources of inspiration for analytical methods used by fPET-FDG researchers. In this study, we present an investigate of how inaccuracies in modeling baseline FDG uptake can introduce artifactual patterns to detrended TAC residuals, potentially introducing spurious (de)activations to general linear model (GLM) analyses. By combining simulations and empirical data from both constant infusion and bolus-plus-constant infusion protocols, we evaluate the effects of various baseline modeling methods, including polynomial detrending, regression against the global mean time-activity curve, and two analytical methods based on tissue compartment model kinetics. Our findings indicate that improper baseline removal can introduce statistically significant artifactual effects, although these effects characterized in this study ([~]2-8%) are generally smaller than those reported by previous literature employing robust sensory stimulation ([~]10-30%). We discuss potential strategies to mitigate this issue, including informed baseline modeling, optimized tracer administration protocols, and careful experimental design. These insights aim to enhance the reliability of fPET-FDG in capturing true metabolic dynamics in neuroimaging research.

neuroscience↗