Biology subjects

Sundaram, P.

Publications and source records attributed to Sundaram, P..

10 recordsLinked to original sources

bioRxiv2026

Signal-to-noise ratio of event-related fields in on-scalp and off-scalp MEG

Abstract Optically pumped magnetometer (OPM) sensors can be placed closer to the scalp than conventional superconducting quantum interference devices (SQUID), resulting in larger magnetoencephalography (MEG) signals from neuronal activity. For event-related sensor data, such as epileptogenic activity or sensory and motor evoked responses, however, OPMs and SQUIDs often differ less in signal-to-noise ratio (SNR) than in signal magnitude. We examined two factors contributing to the relative SNR: the dependence of the signal magnitude on source depth and the effect of scalp-to-sensor distance on the noise level. Simulated MEG data for a current dipole in a spherical head model confirmed that on-scalp sensor placement delivers the largest SNR gain for superficial sources. Depending on the relative overall noise level, there may be a crossover source depth at which SNR is equal for on-scalp and off-scalp sensors and beyond which off-scalp sensors achieve higher SNR. Analysis of the equal-SNR source depth in different-sized spherical head models indicated that, for a given relative noise level, the proportion of the brain where SNR is higher in OPM than in SQUID was larger in small head models, supporting the benefits of OPMs in pediatric studies. To experimentally evaluate noise contributions of brain and non-brain origin to the SNR, we recorded somatosensory evoked fields (SEFs) at varying scalp-to-sensor distances. Generally, both the evoked response magnitude and the noise level were lower when the sensors were further away from the scalp; consequently, the SNR depended less than the signal magnitude on the scalp-to-sensor distance. Comparison of power spectral densities (PSDs) at different sensor-to-scalp distances allowed us to identify whether the dominant noise source was of brain or non-brain origin at different frequency bands. Overall, the results highlight complementary properties of OPMs vs. SQUIDs in terms of SNR, which is of interest when optimizing MEG experiments for specific subject populations and brain regions.

neuroscience↗

bioRxiv2026

Motion tolerance in wearable OPM-MEG using dynamic field nulling

Wearable magnetoencephalography (MEG) enabled by optically pumped magnetometers (OPMs) promises improved comfort and motion tolerance. This is particularly beneficial when measuring brain activity in children who cannot sit still for long periods of time. Compared to cryogenic MEG, wearable MEG allows larger head movements, but they result in artifacts due to uncompensated background fields and reduce source localization accuracy. Spatial filtering methods can partially compensate these motion-induced artifacts, but they are most effective when used in combination with background field nulling. This is because accurate spatial filtering relies on an accurate estimate of the sensor gain and orientation of its sensitive axis. Through simulations, we first deduce the target residual background field that is necessary for accurate dipole localization (< 1 cm) in the presence of head movements. Using our open-source printed circuit board (PCB) coils, we develop a method to dynamically null the background field. We demonstrate that our dynamic field nulling method allows improved localization of somatosensory evoked fields (SEFs) by maintaining the background field below the target residual fields established in the simulations. Our study highlights the importance of tracking both the background field and the head position relative to the background field for quality assurance in wearable MEG.

neuroscience↗

bioRxiv2026

Preclinical evaluation of Brincidofovir in glioblastoma demonstrates improved long term-survival and cytomegalovirus-dependent and independent effects

Cytomegalovirus (CMV) has been implicated in glioblastoma (GBM) progression. Ongoing clinical trials are assessing therapeutic approaches targeting CMV in GBM but to date no new therapy has been approved outside the standard of care. Previous preclinical studies have highlighted the potential of the antiviral drug Cidofovir (CDV) in GBM; however, its clinical use is limited by dose-dependent nephrotoxicity and poor cellular uptake, necessitating high intravenous doses to achieve therapeutic activity. Brincidofovir (BCV), a lipid conjugate of CDV has been developed, which does not induce nephrotoxicity and has significantly greater cellular bioavailability. Here we examined the effects of BCV in a newly established CMV-driven GBM model (SB28) and in patient-derived tumor neurospheres. We show that BCV prolongs survival in vivo and exerts both CMV-dependent and independent antitumor effects. Mechanistically, BCV induces DNA damage and cell cycle dysregulation in GBM cells and inhibits proliferation of patient-derived neurospheres in a dose-dependent manner. These data identify BCV as a dual-action therapeutic that suppresses viral oncomodulation while directly targeting tumor cell viability.

cancer biology↗

bioRxiv2026

Cellular Mechanisms of Transcranial Magnetic Stimulation in Climbing Fibers and Purkinje Neurons in the Cerebellum

Although transcranial magnetic stimulation (TMS) is widely used for brain stimulation, fundamental issues about its underlying mechanisms remain unresolved. We investigated some of these issues experimentally using an intact isolated turtle cerebellum in vitro, employing a novel chamber designed to deliver precisely calibrated induced electric fields along cortical depth. Our results show that single-pulse TMS can directly activate Purkinje cells and climbing fibers, and synaptically activate Purkinje cells via climbing fibers - all within the first 1.2 ms. Specifically, current source density analysis showed that TMS directly (non-synaptically) activated (1) climbing fibers near the bend with intracellular current directed toward the axonal terminals and (2) Purkinje cells directly near the axon initial segment with intracellular current directed toward the distal dendrites. The thresholds for direct activation of climbing fibers and Purkinje cells were found to be very similar, 25 {+/-} 1 V/m. The climbing fibers synaptically activated Purkinje cells, as expected, with intracellular current originating in the proximal dendritic trunk and directed toward the distal dendrites. At higher electric fields (> 58 {+/-} 17 V/m), TMS synaptically activated dendritic currents in Purkinje cells. These results provide new insight into how TMS may activate afferent fibers and cell bodies of cortical neurons.

biophysics↗

bioRxiv2026

Quantifying Cerebellar Signal Detectability in MEG and EEG in Epilepsy Using Anatomically Informed Source Modeling

ObjectiveThe cerebellum is increasingly recognized as a key component of large-scale brain networks implicated in epilepsy, yet its electrophysiological characterization remains limited in noninvasive recordings. This limitation arises from the cerebellums depth, complex folding, and unfavorable source orientations, which challenge conventional magnetoencephalography (MEG) and electroencephalography (EEG). Here, we quantitatively characterize cerebellar signal detectability across modalities and sensor configurations using anatomically informed source modeling at the population level. MethodsWe analyzed clinical MEG and EEG recordings from a large cohort of patients with epilepsy undergoing presurgical evaluation. Cerebellar and cerebral source spaces were constructed using subject-specific anatomical models derived from routine clinical MRI, enabling consistent forward modeling across individuals. Signal-to-noise ratio (SNR) was estimated at individual source locations and summarized at the regional level. In addition to clinical Superconducting quantum interference device (SQUID)-MEG and EEG, multiple on-scalp optically pumped magnetometer (OPM) configurations were evaluated through simulation, including layouts matched to clinical sensor geometries and layouts optimized for posterior fossa coverage. The effects of source orientation, sensor-source distance, and head size on SNR were systematically investigated. ResultsIn routine clinical recordings, cerebellar SNR was consistently lower than superficial cortical reference levels, confirming the limited detectability of cerebellar activity with standard SQUID-MEG and EEG. Reducing sensor-source distance by placing OPMs at SQUID-equivalent locations, i.e., projecting SQUID sensor locations to the scalp, did not improve cerebellar SNR, indicating that proximity alone is insufficient for better detectability of deeper sources. In contrast, cerebellar-optimized OPM layouts produced substantial SNR gains in posterior cerebellar regions. The effects of source orientation influence SNR differences between OPM and EEG (under identical sensor/electrode coverage) but were secondary to depth- and geometry-related constraints. Mediation analysis further demonstrated that relative sensor distance significantly mediated OPM-related advantages in posterior cerebellar regions, particularly in individuals with smaller head sizes. ConclusionsThese findings demonstrate that cerebellar signal detectability is governed primarily by anatomical depth and geometry rather than sensor proximity alone. Anatomically informed source modeling, combined with flexible and region-specific sensor layouts, enables meaningful improvements in cerebellar SNR that are not achievable with fixed-helmet systems. While directly motivated by epilepsy, this framework advances human brain mapping beyond the cerebrum by providing a principled approach for evaluating MEG and EEG sensitivity in deep and highly folded brain structures.

bioengineering↗

bioRxiv2025

Measuring Transcranial Magnetic Stimulation-Induced Electric Fields in Anatomically and Conductively Accurate Rat Head Phantoms

The efficacy of neuromodulation techniques like transcranial magnetic stimulation (TMS), are highly dependent on the geometry and conductivity of the stimulated target of the brain. Although anatomically accurate head models are routinely used for computational simulations of TMS-induced electric (E) felds, there is still a need for realistic phantoms that mimic the anatomy and electrical conductivity of the head. Here, we present a realistic rat brain phantom constructed using advanced 3-d printing technologies. Our phantom allows validation of TMS-induced E-fields using embedded mutually orthogonal triaxial dipole probes (TDP) that can measure induced E-fields along three axes. We tested the TDP probes in the constructed phantom using four TMS coils with different core materials and core geometry. These measurements were then compared to computational simulations using the finite element method (FEM). The rat brain phantoms had a conductivity of roughly 0.5 S/m, which was mimicked in the FEM simulations. When the measured induced e-fields in the phantoms were compared to the simulated results, the measured results were in the same expected range and fairly close to one another with an average error of 5.1%. The peak E-fields (measured vs. simulated) close to the surface of the grey matter were: permender v-tip core (115.3 V/m - 110V/m), permender flat tip core (91.9V/m - 85 V/m), AISI 1010 v-tip core (94.7 V/m - 100 V/m), and AISI 1010 flat-tip core (85.9 V/m - 84 V/m) respectively.

bioengineering↗

bioRxiv2025

Construction of Accurate Turtle Cerebellum Models and their use in Simulating Neuromodulation using the BEM-FMM

Digital representations of Purkinje cells from turtle cerebellum, which have long been to study cellular transmission dynamics and neuroplasticity, are necessary to conduct simulations of neuromodulation methods, including Transcranial Magnetic Stimulation (TMS). Methods: Data collected using microCT with 0.6 um isometric resolution are processed, segmented, and arranged to enable high resolution simulation via the Boundary Element Fast Multipole Method. Results: Fully computer aided design compatible, manifold triangular surface meshes were generated from microCT data and used to simulate cellular electromagnetic response to TMS. Conclusion: Accurate Purkinje cells may be readily generated and manipulated to create representative models of turtle cerebellum. Significance: The techniques employed herein may be used to generate accurate surface mesh of Purkinje cells which can enable computational electromagnetics code verification and serve as the basis for skeletal models used for bidomain biophysical simulations in tools such as NEURON to study neurostimulation dynamics and neuromodulation.

neuroscience↗

bioRxiv2025

Biplanar nulling coil system for OPM-MEG using printed circuit boards

Optically pumped magnetometers (OPMs) are a promising sensor technology for non-invasive measurement of human electrophysiological signals, in particular the magnetoencephalogram (MEG). OPMs do not need cryogenic cooling and can be placed conformal to the subjects scalp, thus greatly reducing the sensor-to-source distance and improving signal sensitivity. OPMs, however, require near-zero background magnetic field to achieve linearity and minimize signal distortion. Prior work has proposed the use of biplanar field nulling coils to remove the uniform and gradient components of the background magnetic field. Biplanar coils have been expensive to construct, involving tedious error-prone manual winding of over 1000 m of copper wire. In this work, we designed and fabricated background field nulling coils (three uniform and three gradient components) on two-layer Printed Circuit Boards (PCBs). We used an open-source software (bfieldtools) to determine the current loops needed to produce the target magnetic field in a 50-cm-diameter spherical volume. We developed a software-based approach to connect the discrete current loops into a continuous conducting path traversing the two layers of the PCB. For ease of manufacture, the designed (1.5 x 1.5 m2) coils were cut along the symmetry axis and printed as pairs of 1.5 x 0.75 m2 PCBs (2 oz Cu), soldered together and mounted on a sliding aluminum frame. The efficiency of the coils (1.3 - 7.1 nT/mA) was similar or higher than previously reported in the literature. We mapped the field inside the target region after field nulling inside our single-layer shielded room and were able to reduce the largest component of the background field from 21 to 2 nT. Using our nulling coil system, we were able to operate OPMs in a lightly shielded room (background field varying from 6.5 to 108 nT in the floor-to-ceiling direction) to record somatosensory evoked fields (SEFs) comparable to those measured using SQUID-based MEG in a 3-layer shielded room. We disseminate the software and hardware as an open-source package opmcoils. This work will facilitate access to more affordable field nulling coils for OPM-MEG and help to realize the potential of OPM-MEG as an accessible sensor technology for use in human neuroscience.

neuroscience↗

bioRxiv2024

Decoding auditory working memory content from EEG aftereffects of auditory-cortical TMS

Working memory (WM), short term maintenance of information for goal directed behavior, is essential to human cognition. Identifying the neural mechanisms supporting WM is a focal point of neuroscientific research. One prominent theory hypothesizes that WM content is carried in "activity-silent" brain states involving short-term synaptic changes. Information carried in such brain states could be decodable from content-specific changes in responses to unrelated "impulse stimuli". Here, we used single-pulse transcranial magnetic stimulation (spTMS) as the impulse stimulus and then decoded content maintained in WM from EEG using multivariate pattern analysis (MVPA) with robust non-parametric permutation testing. The decoding accuracy of WM content significantly enhanced after spTMS was delivered to the posterior superior temporal cortex during WM maintenance. Our results show that WM maintenance involves brain states, which are activity silent relative to other intrinsic processes visible in the EEG signal.

neuroscience↗

bioRxiv2018

Microscopic and Macroscopic Response of a Cortical Neuron to an External Electric Field Computed with the Boundary Element Fast Multipole Method

The goal of this study is to demonstrate how one can compute the activating function and surface charge density resulting from application of an external electric field to a high-resolution realistic neuronal morphology. We use the boundary element fast multipole method (BEM-FMM) on an ordinary computer to accurately perform these computations in under 2-10 minutes for a dense surface mesh of a single neuron with approximately 1.4 million triangles. Prior work used commercial finite element method (FEM) software which required creation of a volumetric tetrahedral mesh between fine neuronal arbor, potentially resulting in prohibitively large volume sizes and long mesh generation times. We used the example of a human pyramidal neuron with an externally applied E-field to show how our approach can quickly and accurately compute the induced surface charge density on the cell surface and the activating function of the cable equation. We found that the induced surface charge density perturbs the macroscopically applied E-field on a microscopic spatial scale. The strength of the perturbation depends on the conductivity contrast; the stronger the contrast, the larger the perturbation. In our example, the induced surface charge density may change the average activating function by up to 75%. We also embedded this neuron model into a detailed macroscopic human head model and simulated a realistic TMS excitation using the BEM-FMM method for the combined model. The solution obtained in this case predicted a smaller activating function error. The difference between the microscopic and the macroscopic effect of the externally applied electric field is of much interest to users of extracellular stimulation techniques and merits further study.

neuroscience↗