Biology subjects

Bansal, P.

Publications and source records attributed to Bansal, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Sequence constraints predispose Class D GPCRs to follow an atypical activation mechanism

The biophysical principles underlying distinct conformational changes in proteins with similar topologies remain poorly understood. Class D G Protein-Coupled Receptors (GPCRs), fungal pheromone-sensing receptors essential for mating and survival, exhibit an atypical activation mechanism compared to other GPCR classes. Unlike Class A GPCRs, which activate through outward movement of TM6, Class D receptors undergo activation via outward displacement of TM7 coupled with inward movement of TM6. To investigate the origin of this atypical process, we employed state-specific generative AI sequence models to design protein sequences corresponding to unique active states, revealing that sequence constraints predispose Class D GPCRs toward this mechanism. We further explored the dynamic basis of activation through millisecond-scale atomistic simulations of STE2, a representative Class D GPCR and therapeutic target for fungal diseases. Using Maximum Entropy VAMPNets, an active learning based adaptive sampling strategy, we efficiently mapped the conformational free energy landscape of STE2. These simulations uncovered multiple intermediate states that have not yet been resolved experimentally and demonstrated that activation in these dimeric proteins involves fully decoupled monomers. Comparative simulations across Classes A, B, D, and F, totaling 4 milliseconds of all-atom molecular dynamics, revealed distinct patterns of electrostatic interactions. In Class D GPCRs, activation disrupts a dense TM7 interaction network while inward TM6 movement enhances electrostatic contacts. In contrast, Class A GPCRs such as CB1R display the opposite trend. Together, these findings show that sequence differences in TM6 and TM7 underlie the unique activation mechanism of STE2, offering new insights into GPCR conformational diversity.

biophysics↗

bioRxiv2026

All roads lead to Rome: Emergence of Mechanistic Divergence Shapes Activation of Class B1 G-Protein Coupled Receptors

Class B1 GPCRs are crucial to maintaining homeostasis along a multitude of vital biochemical pathways. Understanding the activation mechanism of these proteins at both a family and clade-specific level is particularly relevant for designing multi-target agonists, as exemplified by recently designed dual-agonists for GLP-1R and GIPR, for treating obesity. Here, we use 6 milliseconds of unbiased all-atom MD simulations of GCGR, GLP1R, PAC1R, SCTR, PTH1R and CALCR from the four different clades of Class B1 GPCRs to establish the universal mechanism of their activation. We show that the activation of Class B1 GPCRs involves a clade-independent intermediate state characterized by the outward movement of helix 6. We use a combination of Markov state models and transition path theory to show that the activation of these proteins occurs at a millisecond timescale. We identify characteristic molecular locks that are conserved at a clade-level, showcasing the uniqueness among the activation mechanisms of these proteins. We show that these proteins show similar inactive and active states, but show unique activation mechanisms at a residue level. These sites can be targeted directly or allosterically to design therapeutics targeting a specific clade of proteins. Thus, this study provides an integrated atomistic view of the activation for Class B1 GPCRs from a mechanistic, thermodynamic and kinetic perspective.

biophysics↗

bioRxiv2024

Dbf4-Dependent Kinase Finetunes INO80 Function at Chromosome Replication Origins

The highly conserved Dbf4-Dependent Kinase (DDK) plays a pivotal role in the nucleus during S phase, where it directly phosphorylates the replicative helicase, the minichromosome maintenance (MCM) complex. This leads to the initiation of chromosome replication. However, aside from the MCM complex, few other targets have been identified to date, leaving DDK an understudied kinase. Here, we describe a two-pronged mass spectrometry-based approach and define the nuclear DDK-dependent phosphoproteome, which consists of approximately 400 phosphorylation events. Within this network, we found that DDK directly phosphorylates the Arp8 subunit of the multi-subunit chromatin remodeler complex INO80. Arp8 phosphorylation stabilises INO80s intramolecular complex integrity, which finetunes its nucleosome spacing activity at replication origins. This adjustment of origin chromatin architecture stimulates replication and is important for the response to replication stress. Our results represent a significant advance in our understanding of the molecular mechanisms underlying the regulation of replication origins.

biochemistry↗

bioRxiv2024

Two neuropeptides that promote blood-feeding in Anopheles stephensi mosquitoes

Animals routinely need to make decisions about what to eat and when. These decisions are influenced not only by the availability and quality of food but also by the internal state of the animal, which needs to compute and give weights to these different variables before making a choice. Feeding preferences of female mosquitoes exemplify this behavioural plasticity. Both male and female mosquitoes usually feed on carbohydrate-rich sources of nectar or sap, but the female also feeds on blood, which is essential for egg development. This blood-appetite is modulated across the females reproductive cycle, yet little is known about the factors that bring it about. We show that mated, but not virgin Anopheles stephensi females, a major vector of urban malaria in the Indian sub-continent and West Africa, suppress blood feeding between a blood meal and oviposition. We identify several candidate genes through transcriptomics of blood-deprived and -sated An. stephensi central brains that could modulate this behaviour. We show that short neuropeptide F (sNPF) and RYamide (RYa) act together to promote blood feeding and identify a cluster of cells in the subesophageal zone that expresses sNPF transcripts only in the blood-hungry state. Such females also have more sNPF transcripts in their midguts. Based on these data, we propose a model where increased sNPF levels in the brain and gut promote a state of blood-hunger, which drives feeding behaviour either by sNPFs action in the two tissues independently or via a communication between them. This occurs in the context of the action of RYa in the brain.

animal behavior and cognition↗

bioRxiv2024

Hypothalamic dopamine neuron activity is modulated by caloric states and amphetamine abuse in zebrafish larvae

Dopaminergic (DA) neuron activity is affected by reward and stress-inducing entities such as food and drugs of abuse, and different DA neuron populations can respond distinctly to these stimuli. Interaction between both stimuli significantly alters the dynamics of DA release in different DA populations. Additionally, these stimulating entities can affect the interconnections among different DA populations by impairing their correspondence with each other. However, limited studies have been performed that could point to the effect of interaction between AMPH and caloric states on DA neurons and their inter-correlation. This study explores the individual and interactive effect of two caloric states, ad-libitum fed (AL) and food deprived (FD), and acute exposure to a stimulant drug (amphetamine) in two different DA neurons in the hypothalamus of zebrafish larvae. We used a transgenic zebrafish line Tg(th2:GCaMP7s), which expresses a calcium indicator (GCaMP7s) in A11(Posterior Tuberculum) and a part of A14 (Caudal Hypothalamus and Intermediate Hypothalamus) DA populations located in the hypothalamus of the larval zebrafish. The larvae were subjected to acute FD and ad AL feeding followed by acute treatment with 0.7uM and 1.5uM doses of AMPH. We recorded calcium activity and quantified fluorescence change, activity duration, peak rise/fall time, and latency in the spikes of the DA neurons. Our results show that baseline DA neuron activity amplitude, spike duration, and correlation between inter- and intra-DA neurons were higher in the FD than in the AL state. Dose-dependent AMPH treatment further increased the activity intensity of the aforementioned parameters in the neuron spikes in the FD state. The DA activity correlation and spike latency were dose-dependently impaired in both DA populations. These results suggest that different DA populations in the brain exhibit a similar activity trend in response to caloric states and AMPH, where the AMPH-mediated intensity change in the activity was dose-dependent.

neuroscience↗

bioRxiv2024

Modulation of locomotion and motor neuron response by the cohesive effect of acute and chronic feeding states and acute d-amphetamine treatment in zebrafish larvae.

Amphetamine (AMPH) increases locomotor activities in animals, and the locomotor response to AMPH is further modulated by caloric deficits such as food deprivation and restriction. The increment in locomotor activity regulated by AMPH-caloric deficit concomitance can be further modulated by varying feeding schedules (e.g. acute and chronic food deprivation and acute feeding after chronic food deprivation). However, the effects of different feeding schedules on AMPH-induced locomotor activity are yet to be explicated. Here, we have explored the stimulatory responses of acutely administered d-amphetamine in locomotion under systematically varying feeding states (fed/sated and food deprivation) and schedules (chronic and acute) in zebrafish larvae. We used wild-type and transgenic[Tg(mnx1:GCaMP5)] zebrafish larvae and measured swimming activity and spinal motor neuron activity in vivo in real-time in time-elapsed and cumulative manner pre- and post-AMPH treatment. Our results showed that locomotion and motor neuron activity increased in both chronic and acute food deprivation post-AMPH treatment cumulatively. A steady increase in locomotion was observed in acute food-deprivation compared to an immediate abrupt increase in chronic food-deprivation state. The ad libitum-fed larvae exhibited a moderate increase both in locomotion and motor neuron activity. Conversely to all other caloric states, food-sated (acute feeding after chronic food deprivation) larvae moved moderately less and exhibited a mild decrease in motor neuron activity after AMPH treatment. These results point to the importance of the feeding schedule in modulating amphetamines characteristic stimulatory response on behavior and motor neurons.

neuroscience↗

bioRxiv2023

Isogenic hiPSC models of Turner Syndrome reveal shared roles of inactive X and Y in the human cranial neural crest network

SUMMARYModeling the developmental etiology of viable human aneuploidy can be challenging in rodents due to syntenic boundaries, or primate-specific biology. In humans, monosomy-X (45,X) causes Turner syndrome (TS), altering craniofacial, skeletal, endocrine, and cardiovascular development, which in contrast remain unaffected in 39,X-mice. To learn how human monosomy-X may impact early embryonic development, we turned to human 45,X and isogenic euploid induced pluripotent stem cells (hiPSCs) from male and female mosaic donors. Because neural crest (NC) derived cell types are hypothesized to underpin craniofacial and cardiovascular changes in TS, we performed a highly-powered differential expression study on hiPSC-derived anterior neural crest cells (NCCs). Across three independent isogenic panels, 45,X NCCs show impaired acquisition of PAX7+SOX10+ markers, and disrupted expression of other NCC-specific genes, relative to their isogenic euploid controls. In particular, 45,X NCCs increase cholesterol biosynthesis genes while reducing transcripts that feature 5 terminal oligopyrimidine (TOP) motifs, including those of ribosomal protein and nuclear-encoded mitochondrial genes. Such metabolic pathways are also over-represented in weighted co-expression gene modules that are preserved in monogenic neurocristopathy. Importantly, these gene modules are also significantly enriched in 28% of all TS-associated terms of the human phenotype ontology. Our analysis identifies specific sex-linked genes that are expressed from two copies in euploid males and females alike and qualify as candidate haploinsufficient drivers of TS phenotypes in NC-derived lineages. This study demonstrates that isogenic hiPSC-derived NCC panels representing monosomy-X can serve as a powerful model of early NC development in TS and inform new hypotheses towards its etiology.

developmental biology↗

bioRxiv2022

Understanding Supramolecular Assembly of Supercharged Proteins

Ordered supramolecular assemblies of supercharged synthetic proteins have recently been created using electrostatic interactions between oppositely charged proteins. Despite recent progress, the fundamental mechanisms governing the assembly process between oppositely supercharged proteins are not fully understood. In this work, we use a combination of experiments and computational modeling to systematically study the supramolecular assembly process for a series of oppositely supercharged green fluorescent protein (GFP) variants. Our results show that the assembled structures of oppositely supercharged proteins critically depend on surface charge distributions. In addition, net charge is a sufficient molecular descriptor to predict the interaction fate of oppositely charged proteins under a given set of solution conditions (e.g., ionic strength). Interestingly, our results show that a large excess of charge is necessary to nucleate assembly and that charged residues that are not directly involved in interprotein interactions contribute to a substantial fraction ([~]30%) of the interaction energy between oppositely charged proteins via long-range electrostatic interactions. Dynamic subunit exchange experiments enabled by Forster resonance energy transfer (FRET) further show that relatively small, 16-subunit assemblies of oppositely charged proteins have kinetic lifetimes on the order of [~]10-40 minutes, which is governed by protein composition and solution conditions. Overall, our work shows that a balance between kinetic stability and electrostatic charge ultimately determine the fate of supramolecular assemblies of supercharged proteins. Broadly, our results inform how protein supercharging can be used to generate different ordered supramolecular assemblies from a single parent protein building block.

bioengineering↗

bioRxiv2022

Activation Mechanism of the Human Smoothened Receptor

Smoothened (SMO) is a membrane protein of the Class F subfamily of G-Protein Coupled Receptors (GPCRs) and maintains homeostasis of cellular differentiation. SMO undergoes conformational change during activation, transmitting the signal across the membrane, making it amenable to bind to its intracellular signaling partner. Receptor activation has been studied at length for Class A receptors, but the mechanism of Class F receptor activation remain unknown. Agonists and antagonists bound to SMO at sites in the Transmembrane Domain (TMD) and the Cysteine Rich Domain have been characterized, giving a static view of the various conformations SMO adopts. While the structures of the inactive and active SMO outline the residue-level transitions, a kinetic view of the overall activation process remains unexplored for Class F receptors. We describe SMOs activation process in atomistic detail by performing 300 s of molecular dynamics simulations and combining it with Markov state model theory. A molecular switch, conserved across Class F and analogous to the activation-mediating D-R-Y motif in Class A receptors, is observed to break during activation. We also show that this transition occurs in a stage-wise movement of the transmembrane helices - TM6 first, followed by TM5. To see how modulators affect SMO activity, we simulated agonist and antagonist-bound SMO. We observed that agonist-bound SMO has an expanded hydrophobic tunnel in SMOs core TMD, while antagonist-bound SMO shrinks this tunnel, further supporting the hypothesis that cholesterol travels through a tunnel inside Smoothened to activate it. In summary, this study elucidates the distinct activation mechanism of Class F GPCRs and shows that SMOs activation process rearranges the core transmembrane domain to open a hydrophobic conduit for cholesterol transport.

biophysics↗

bioRxiv2022

Food deprivation modulates heart rate, motor neuron, and locomotion responses to acute administration of d-amphetamine in zebrafish larvae

Psychostimulant drugs are so named because they alter the cardiac, brain and behavioral responses in humans and other animals. Acute food deprivation or chronic food restriction potentiates the stimulatory effects of abused drugs and increases the propensity for relapse to drug seeking in drug-experienced animals. The mechanisms by which hunger affects cardiac and behavioral activities are only beginning to be elucidated. Moreover, changes in motor neuron activities at the single neuron level induced by the stimulants, and their modulation by hunger, remain unknown. Here we investigated how the state of hunger affects responses to d-amphetamine by measuring locomotion, cardiac output, and individual motor neuron activity in zebrafish larvae. We used wild-type larval zebrafish to record behavioral and cardiac responses and the larvae of mnx1:GCaMP transgenic zebrafish to record motor neuron responses. Acute administration of d-amphetamine in sated larvae did not induce a significant change in the motor responses (swimming distances, tail activity), heart rate, or motor neuron firing frequency to the stimulant. However, food deprivation enhanced amphetamine-evoked responses significantly. The results extend the finding that signals arising from food deprivation are a key potentiator of the drug responses induced by d-amphetamine to the zebrafish model. The larval zebrafish is an ideal model to further elucidate this interaction and identify key neuronal substrates that may increase vulnerability to drug reinforcement, drug-seeking and relapse.

animal behavior and cognition↗

bioRxiv2022

A VPS15-like kinase regulates apicoplast biogenesis and autophagy by promoting PI3P generation in Toxoplasma gondii

Phosphoinositides are important second messengers that regulate key cellular processes in eukaryotes. While it is know that a single phosphoinositol-3 kinase (PI3K) catalyses the formation of 3-phosphorylated phosphoinositides (PIPs) in apicomplexan parasites Plasmodium and Toxoplasma, how its activity and PI3P formation is regulated has remained unknown. Present studies involving a unique Vps15 like protein (TgVPS15) in Toxoplasma gondii provide insights into the regulation of phosphatidyl-3-phosphate (PI3P) generation and unravel a novel pathway that regulates parasite development. Detailed investigations suggested that TgVPS15 regulates PI3P formation in Toxoplasma gondii, which is important for the inheritance of the apicoplast-a plastid like organelle present in most apicomplexans and parasite replication. Interestingly, TgVPS15 also regulates autophagy in T. gondii under nutrient-limiting conditions as it promotes autophagosome formation. For both these processes, TgVPS15 uses PI3P-binding protein TgATG18 and regulates trafficking and conjugation of TgATG8 to the apicoplast and autophagosomes, which is important for biogenesis of these organelles. TgVPS15 has a protein kinase domain but lacks several key residues conserved in conventional protein kinases. Interestingly, two critical residues in its active site are important for PI3P formation and parasitic functions of this kinase. Collectively, these studies unravel a signalling cascade involving TgVPS15, a novel effector of PI3-kinase in T. gondii and possibly other Apicomplexa, that regulate critical processes like apicoplast biogenesis and autophagy.

cell biology↗

bioRxiv2022

A dynamic in vitro model of Down Syndrome neurogenesis with Trisomy 21 gene dosage correction

ABSTRACT/SUMMARYExcess gene dosage from human chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental as well as acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this question in a model of DS neurogenesis, we generated trisomy 21 (T21) human induced pluripotent stem cells (hiPSCs) alongside otherwise isogenic euploid controls from mosaic DS fibroblasts, and integrated an inducible XIST transgene on one chr21 copy. Monoallelic chr21 silencing by XIST was near-complete and irreversible in hiPSCs. Differential expression reveals T21 neural lineages and T21 hiPSCs suppress similar translation and mitochondrial pathways, and activate cellular stress responses. When XIST is induced before the neural progenitor stage, T21 dosage correction mitigates a pronounced skew towards astrogenesis in differentiation. Because our transgene remained inducible in post-mitotic T21 neurons and astrocytes, we demonstrate XIST efficiently represses genes even after terminal differentiation, which will empower exploration of cell type-specific T21 phenotypes that remain responsive to chr21 dosage.

developmental biology↗

bioRxiv2021

Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta

SUMMARY/ABSTRACTMammalian sex chromosomes encode homologous X/Y gene pairs that were retained on the male Y and escape X chromosome inactivation (XCI) in females. Inferred to reflect X/Y-pair dosage sensitivity, monosomy X is a leading cause of miscarriage in humans with near full penetrance. This phenotype is shared with many other mammals but not the mouse, which offers sophisticated genetic tools to generate sex chromosomal aneuploidy but also tolerates its developmental impact. To address this critical gap, we generated X-monosomic human induced pluripotent stem cells (hiPSCs) alongside otherwise isogenic euploid controls from male and female mosaic samples. Phased genomic variants of these hiPSC panels enable systematic investigation of X/Y dosage-sensitive features using in vitro models of human development. Here, we demonstrate the utility of these validated hiPSC lines to test how X/Y-linked gene dosage impacts a widely-used model for the human syncytiotrophoblast. While these isogenic panels trigger a GATA2/3 and TFAP2A/C -driven trophoblast gene circuit irrespective of karyotype, differential expression implicates monosomy X in altered levels of placental genes, and in secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). Remarkably, weighted gene co-expression network modules that significantly reflect these changes are also preserved in first-trimester chorionic villi and term placenta. Our results suggest monosomy X may skew trophoblast cell type composition, and that the pseudoautosomal region likely plays a key role in these changes, which may facilitate prioritization of haploinsufficient drivers of 45,X extra-embryonic phenotypes.

developmental biology↗

bioRxiv2020

A CDK-regulated chromatin segregase promoting chromosome replication

The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the identification of a novel class of chromatin remodeling enzyme, entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA+-ATPase that assembles into ~ 1 MDa hexameric complexes capable of segregating histones from DNA. Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that Yta7s enzymatic activity is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a novel mechanism of how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.

biochemistry↗

bioRxiv2020

Contiguous Erosion of the Inactive X in Human Pluripotency Concludes With Global DNA Hypomethylation

Female human pluripotent stem cells (hPSCs) are prone to undergoing X chromosome erosion (XCE), a progressive loss of key epigenetic features on the inactive X that initiates with repression of XIST, the long non-coding RNA required for X inactivation. As a result, previously silenced genes on the eroding X (Xe) reactivate, some of which are thought to provide selective advantages. To-date, the sporadic and progressive nature of XCE has largely obscured its scale, dynamics, and key transition events. To address this knowledge gap, we performed an integrated analysis of DNA methylation (DNAme), chromatin accessibility, and gene expression across hundreds of hPSC samples. Differential methylation across the Xe enables ordering female hPSCs across a trajectory of XCE from initiation to terminal stages. Our results identify a crucial cis-regulatory element for XIST expression, trace contiguously growing domains of reactivation to a few euchromatic origins on the Xi, and indicate that the late-stage Xe impairs DNAme genome-wide. Surprisingly, from this altered epigenetic landscape emerge select features of naive pluripotency, suggesting its link to X chromosome dosage may be partially conserved in human embryonic development.

genomics↗

bioRxiv2020

An interaction network of RNA-binding proteins involved in Drosophila oogenesis

During Drosophila oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole Drosophila ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.

biochemistry↗

bioRxiv2019

Enzyme annotation in UniProtKB using Rhea

MotivationTo provide high quality computationally tractable enzyme annotation in UniProtKB using Rhea, a comprehensive expert-curated knowledgebase of biochemical reactions which describes reaction participants using the ontology ChEBI (Chemical Entities of Biological Interest).\n\nResultsWe replaced existing textual descriptions of biochemical reactions in UniProtKB with their equivalents from Rhea, which is now the standard for annotation of enzymatic reactions in UniProtKB. We developed improved search and query facilities for the UniProt website, REST API, and SPARQL endpoint that leverage the chemical structure data, nomenclature, and classification that Rhea and ChEBI provide.\n\nAvailability and ImplementationUniProtKB at https://www.uniprot.org/; UniProt REST API at https://www.uniprot.org/help/api; UniProt SPARQL endpoint at https://sparql.uniprot.org/sparql; Rhea at https://www.rhea-db.org/.\n\nContactanne.morgat@sib.swiss

bioinformatics↗

bioRxiv2018

Safety of transcranial focused ultrasound for human neuromodulation

BackgroundLow intensity transcranial focused ultrasound (tFUS) is a new method of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. tFUS offers high spatial resolution and adjustable focal lengths for precise neuromodulation of discrete regions in the human brain. Before the full potential of low intensity ultrasound for research and clinical application can be investigated, data on the safety of this technique is indicated.\n\nObjective/HypothesisTo provide an initial evaluation of the safety of tFUS for human neuromodulation through participant report and neurological assessment surrounding pilot investigation of tFUS for neuromodulation.\n\nMethodsParticipants (N = 120) that were enrolled in one of seven human ultrasound neuromodulation studies at the University of Minnesota (2015 - 2017) were queried to complete a follow-up Participant Report of Symptoms questionnaire assessing their self-reported experience and tolerance to participation in tFUS research and the perceived relation of symptoms to tFUS.\n\nResultsA total of 64/120 participant (53%) responded to follow-up requests to complete the Participant Report of Symptoms questionnaire. During the conduct of the seven studies in this report, none of the participants experienced serious adverse effects. From the post-hoc assessment of safety using the questionnaire, 7/64 reported mild to moderate symptoms, that were perceived as possibly or probably related to participation in tFUS experiments. These reports included neck pain, problems with attention, muscle twitches and anxiety. The most common unrelated symptoms included sleepiness and neck pain. There were initial transient reports of mild neck pain, scalp tingling and headache that were extinguished upon follow-up. No new symptoms were reported upon follow up out to 1 month.\n\nConclusions(s)To date, in the literature and including this report, no serious adverse events have been reported as a result of low intensity tFUS for human neuromodulation. Here, we report new data on minor transient events. As currently employed with the parameters used in the studies in this report, tFUS looks to be a safe form of transient neuromodulation in humans.

neuroscience↗