Biology subjects

Russo, S.

Publications and source records attributed to Russo, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Single-cell spatial atlas of high-grade serous ovarian cancer unveils MHC class II as a key driver of spatial tumor ecosystems and clinical outcomes

The tumor microenvironment (TME) is a complex network of interactions between malignant and host cells, yet its orchestration in advanced high-grade serous ovarian carcinoma (HGSC) remains poorly understood. We present a comprehensive single-cell spatial atlas of 280 metastatic HGSCs, integrating high-dimensional imaging, genomics, and transcriptomics. Using 929 single-cell maps, we identify distinct spatial domains associated with phenotypically heterogeneous cellular compositions, and demonstrate that immune cell co-infiltration at the tumor-stroma interface significantly influences clinical outcomes. To uncover the key drivers of the tumor ecosystem, we developed CEFIIRA (Cell Feature Importance Identification by RAndom forest), which identified tumor cell-intrinsic MHC-II expression as a critical predictor of prolonged survival, independent of clinicomolecular profiles. Validation with external datasets confirmed that MHC-II-expressing cancer cells drive immune infiltration and orchestrate spatial tumor-immune interactions. Our atlas offers novel insights into immune surveillance mechanisms across HGSC clinicomolecular groups, paving the way for improved therapeutic strategies and patient stratification.

cancer biology↗

bioRxiv2024

Layer 6 corticothalamic neurons induce high gamma oscillations through cortico-cortical and cortico-thalamo-cortical pathways

Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation are shaped by the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway in awake, head-fixed mice, we presented ramp-and-hold light at different intensities while recording neural activity in the primary somatosensory barrel cortex (S1) and the ventral posteromedial nucleus (VPm) of the thalamus using silicon probes. We found that the activation of S1 L6CT neurons induces high-frequency LFP oscillations in S1 that are modulated in frequency, but not in amplitude, across light intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the temporal evolution of firing rate in S1 and VPm. While most S1 neurons were steadily suppressed, VPm and S1 Layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to facilitated within 500 ms, suggesting differential recruitment of the intracortical vs cortico-thalamo-cortical pathways. Finally, we found that LFP frequency selectively correlates with VPm firing rate. Taken together, our data suggest that L6CT neurons sculpt the frequency of S1 LFP high gamma oscillations through cortico-thalamo-cortical circuits, linking the recurrent interactions mediated by L6CT neurons to the high gamma oscillations observed across physiological and pathological conditions. Significance StatementLayer 6 corticothalamic (L6CT) neurons are strategically positioned to modulate the cortex and the thalamus allowing them to engage distinct, yet interlocked, circuits. Here we show that the activation of L6CT neurons in the mouse primary somatosensory cortex induces fast cortical oscillations through the coordinated engagement of cortico-thalamo-cortical and intracortical pathways. Our work reveals that these two L6CT-mediated pathways exert competing effects: while intracortical connections suppress cortical spiking, the activity of the cortico-thalamo-cortical loop rapidly evolves, facilitating cortical spiking. We demonstrate that the cortico-thalamo-cortical pathway operates on a faster timescale than the intracortical pathway and critically shapes cortical oscillation frequency. These findings reveal how the unique position of corticothalamic neurons allows them to flexibly and dynamically modulate the thalamocortical network.

neuroscience↗

bioRxiv2024

Spike Reliability is Cell-Type Specific and Shapes Excitation and Inhibition in the Cortex

Neurons encode information in the highly variable spiking activity of neuronal populations, so that different repetitions of the same stimulus can generate action potentials that vary significantly in terms of the count and timing. How does spiking variability originate, and does it have a functional purpose? Leveraging the Allen Institute cell types dataset, we relate the spiking reliability of cortical neurons in-vitro during the intracellular injection of current resembling synaptic inputs to their morphologic, electrophysiologic, and transcriptomic classes. Our findings demonstrate that parvalbumin+ (PV) interneurons, a subclass of inhibitory neurons, show high reliability compared to other neuronal subclasses, particularly excitatory neurons. Through computational modeling, we predict that the high reliability of PV interneurons allows for strong and precise inhibition in downstream neurons, while the lower reliability of excitatory neurons allows for integrating multiple synaptic inputs leading to a spiking rate code. These findings illuminate how spiking variability in different neuronal classes affect information propagation in the brain, leading to precise inhibition and spiking rate codes.

neuroscience↗

bioRxiv2024

Unexpected events modulate context signaling in VIP and excitatory cells of the visual cortex

The visual cortex predicts incoming sensory stimuli through internal models of the world. Unexpected stimuli that violate these predictions update internal models and drive adaptation. Cortical inhibitory neurons, particularly VIP (vasoactive intestinal peptide) interneurons, are suggested to play a key role in representing unexpected stimuli, given their robust firing following unexpected omissions of familiar images. Importantly, this response is stimulus non-specific, raising an important question about what information it conveys. Given their unique connectivity with other cell types and brain areas, we hypothesized that during unexpected events, VIP neurons encode contextual information, defined as neuronal activity that is not driven by the stimulus itself. To test this hypothesis, we analyzed the Allen Institute Visual Behavior dataset, in which mice viewed repeated familiar images and unexpected omissions of these images while two-photon calcium imaging data from different cell types and visual areas were recorded. Using dimensionality reduction techniques, we found that omissions trigger contextual signaling in VIP neurons in the primary visual cortex (V1) and the lateral medial (LM) visual area, particularly in the superficial layers. Similarly, contextual coding was enhanced in excitatory neurons following omissions. This contrasted sharply with the excitatory response to expected images, during which contextual information was substantially suppressed. Our results suggest that unexpected events activate VIP neurons, which subsequently propagate contextual information across the cortical network. This potentially facilitates the integration of context within the cortical network, and leads to updated predictions about our dynamic environment.

neuroscience↗

bioRxiv2024

Male and female variability in response to chronic stress and morphine in C57BL/6J, DBA/2J, and their BXD progeny

Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and thereby more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions--specifically gene x chronic stress--here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J. Utilizing the chronic social defeat stress (CSDS) and chronic variable stress (CVS) paradigms, we first showed sexual dimorphism in the behavioral stress response between the mouse strains. Further, we observed an interaction between genetic background and vulnerability to prolonged exposure to non-social stressors. Finally, we found that DBA/2J and C57BL/6J mice pre-exposed to stress displayed differences in morphine sensitivity. Our results support the hypothesis that genetic variation in predisposition to stress responses influences morphine sensitivity and is likely to modulate the development of drug addiction.

neuroscience↗

bioRxiv2024

MARK2/MARK3 kinases are catalytic co-dependencies of YAP/TAZ in human cancer

The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. Here, we used paralog co-targeting CRISPR screens to identify the kinases MARK2/3 as absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts. Underlying this observation is direct MARK2/3-dependent phosphorylation of NF2 and YAP/TAZ, which effectively reverses the tumor suppressive activity of the Hippo module kinases LATS1/2. To simulate targeting of MARK2/3, we adapted the CagA protein from H. pylori as a catalytic inhibitor of MARK2/3, which we show exerts anti-tumor activity in vivo. Together, these findings reveal MARK2/3 as powerful co-dependencies of YAP/TAZ in human cancer; targets that may allow for pharmacology that restores Hippo pathway-mediated tumor suppression.

cancer biology↗

bioRxiv2024

Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans

Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits which contribute to the associated evoked potentials (EPs). Here we find that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the subjects behavioral state. We optogenetically dissect the underlying circuit in mice, demonstrating that the late component of these EPs is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with the bursting frequency and synchronicity of thalamic neurons, modulated by the subjects behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that the cortical stimulation engages cortico-thalamo-cortical circuits highly preserved across different species and stimulation modalities. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/578243v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@cae203org.highwire.dtl.DTLVardef@1bc5223org.highwire.dtl.DTLVardef@b48e43org.highwire.dtl.DTLVardef@1e7fe34_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Chemokine receptor 5 signaling in PFC mediates stress susceptibility in female mice

Chronic stress induces changes in the periphery and the central nervous system (CNS) that contribute to neuropathology and behavioral abnormalities associated with psychiatric disorders. In this study, we examined the impact of peripheral and central inflammation during chronic social defeat stress (CSDS) in female mice. Compared to male mice, we found that female mice exhibited heightened peripheral inflammatory response and identified C-C motif chemokine ligand 5 (CCL5), as a stress-susceptibility marker in females. Blocking CCL5 signaling in the periphery promoted resilience to CSDS. In the brain, stress-susceptible mice displayed increased expression of C-C chemokine receptor 5 (CCR5), a receptor for CCL5, in microglia in the prefrontal cortex (PFC). This upregulation was associated with microglia morphological changes, their increased migration to the blood vessels, and enhanced phagocytosis of synaptic components and vascular material. These changes coincided with neurophysiological alterations and impaired blood-brain barrier (BBB) integrity. By blocking CCR5 signaling specifically in the PFC were able to prevent stress-induced physiological changes and rescue social avoidance behavior. Our findings are the first to demonstrate that stress-mediated dysregulation of the CCL5-CCR5 axis triggers excessive phagocytosis of synaptic materials and neurovascular components by microglia, resulting in disruptions in neurotransmission, reduced BBB integrity, and increased stress susceptibility. Our study provides new insights into the role of cortical microglia in female stress susceptibility and suggests that the CCL5-CCR5 axis may serve as a novel sex-specific therapeutic target for treating psychiatric disorders in females.

animal behavior and cognition↗

bioRxiv2023

Monomethylation of Lysine 27 at Histone 3 Confers Lifelong Susceptibility to Stress

Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling, and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice exposed to early life stress (ELS) or to chronic social defeat stress (CSDS) in adulthood displayed increased enrichment of H3K27me1, and transient decreases in H3K27me2, in the nucleus accumbens (NAc), a key brain-reward region. Stress induction of H3K27me1 was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which is induced by chronic stress and controls H3K27 methylation patterns. Overexpression of the VEFS domain led to social, emotional, and cognitive abnormalities, and altered excitability of NAc D1 mediums spiny neurons. Together, we describe a novel function of H3K27me1 in brain and demonstrate its role as a "chromatin scar" that mediates lifelong stress susceptibility.

neuroscience↗

bioRxiv2023

Divergent roles for caspase-8 and MLKL in high-fat diet induced obesity and NAFLD in mice

Cell death frequently occurs in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in apoptotic caspase-8 in myeloid cells, or the essential necroptotic regulators, Receptor-interacting protein kinase-3 (RIPK3) and Mixed lineage kinase domain-like (MLKL), that RIPK3-caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and NAFLD upon high-fat diet feeding. In contrast, MLKL, divergent to RIPK3, contributes to both obesity and NAFLD in a manner largely independent of inflammation. We also uncover that MLKL regulates the expression of molecules involved in lipid uptake, transport and metabolism and, congruent with this, we discover a shift in the hepatic lipidome upon MLKL deletion. Collectively, these findings highlight MLKL as an attractive therapeutic target to combat the growing obesity pandemic and metabolic disease.

immunology↗

bioRxiv2022

Brain-wide oscillatory network selectively encodes aggression

Aggression is a psychological state characterized by intent to harm oneself or others, and often manifests as hostile, harmful, or violent action. Social aggression can aid an organism in securing access to resources1,2, or it can impair group function and survival in behavioral pathology3-5. Since many brain regions contribute to multiple social behaviors6-8, expanded knowledge of how the brain distinguishes between social states would enable the development of interventions that suppress violent action, while leaving other social behaviors intact. Here we showed that a murine aggressive internal state is encoded by a widespread network. This network is organized by prominent and synchronized theta (4-11 Hz) and beta (14-30 Hz) oscillations that relay through the medial prefrontal cortex, and couples to widespread cellular firing. Strikingly, network activity during social isolation was found to encode the trait aggressiveness of mice, and causal cellular manipulations known to impact aggression were found to modulate the networks activity. We next established that this network mediates aggression using closed-loop stimulation of medial prefrontal cortex and causal mediation analysis. Finally, we deployed Long-term integration of Circuits using connexins (LinCx) to selectively edit a key circuit within the network from the medial prefrontal cortex to nucleus accumbens. Editing this circuit chronically suppressed violent action while leaving non-aggressive social behavior intact.

neuroscience↗

bioRxiv2022

Formulating a TMEM176B blocker in nanoparticles uncouples its paradoxical roles in innate and adaptive antitumoral immunity.

The immunoregulatory cation channel TMEM176B plays a dual role in tumor immunity. On one hand, TMEM176B promotes antigen cross-presentation to CD8+ T cells by regulating phagosomal pH in dendritic cells (DCs). On the other hand, TMEM176B inhibits NLRP3 inflammasome activation through ionic mechanisms in DCs, monocytes and macrophages. Moreover, the TMEM176B blocker BayK8644 controls tumor progression through mechanisms involving inflammasome activation in prophylactic but not in therapeutic protocols. We speculated that the limited therapeutic efficacy of the compound may be linked to its potential capacity to inhibit antigen cross-presentation. Here we show that free BayK8644 inhibits antigen cross-presentation by splenic DCs. To prevent such inhibition, we reasoned that formulating BayK8644 in nanoparticles may delay the release of the compound in endosomes. Avoiding TMEM176B inhibition during the first 30 minutes of nanoparticle internalization by DCs may allow efficient cross-presentation to occur during this critical time frame. Indeed, we observed that NP-PEG-BayK8644 did not inhibit antigen cross-presentation, in contrast to the free compound. Moreover, NP-PEG-BayK8644 triggered inflammasome activation in a Tmem176b-dependent manner. We then injected eNP-PEG or NP-PEG-BayK8644 to mice bearing established tumors. NP-PEG-BayK8644 significantly controlled tumor growth and mice survival, as compared to eNP-PEG and free BayK8644, in a Tmem176b-dependent manner in mouse melanoma and lymphoma tumors. Responding animals treated with NP-PEG-BayK8644 showed reinforced tumor infiltration by total and tumor-specific CD8+ T cells. Overall, we rationally developed a formulating method of BayK8644 that improves its anti-tumoral therapeutic efficacy by uncoupling the dual role of TMEM176B on innate and adaptive immunity.

immunology↗

bioRxiv2022

The ZNF687 mutation of Paget's disease associated with giant cell tumour causes severe bone remodelling alteration as a result of a deregulated osteoclast transcriptional program

Pagets disease (PDB) is a late-onset bone remodelling disorder with a broad spectrum of symptoms and complications. One of the most aggressive forms is caused by the P937R mutation in the ZNF687 gene. Although the genetic involvement of ZNF687 in PDB has been extensively studied, the molecular mechanisms underlying this association remains unclear. Here, we describe the first Zfp687 knock-in mouse model and demonstrate that the mutation recapitulates the PDB phenotype, showing a severe bone remodelling alteration. Through micro-computed tomography analysis, we observed that 8-month-old mice showed a mainly osteolytic phase, with a significant decrease in the trabecular bone volume affecting the femurs and the vertebrae of both heterozygous and homozygous mutant mice. In contrast, osteoblast activity was deregulated, beginning to produce disorganised bone. Noteworthy, this phenotype became pervasive in 16-month-old mice, where osteoblast function overtook bone resorption as the predominant event, as highlighted by the presence of woven bone in histological analyses, consistent with the PDB phenotype. Furthermore, we detected osteophytes and intervertebral disc degeneration, outlining for the first time the link between osteoarthritis and PDB in a PDB mouse model. Finally, we generated CRISPR-Cas9-based Zfp687 knock-out RAW 264.7 cells, and noted a remarkable impairment of osteoclast differentiation capacity, reinforcing the relevance of Zfp687 during this process. RNA-sequencing on wild type and KO clones identified a set of genes involved in osteoclastogenesis under the control of Zfp687, i.e., Tspan7, Cpe, Vegfc, and Ggt1. Thus, this study established an essential role of Zfp687 in the regulation of bone remodelling, and may offer the potential to therapeutically treat PDB.

cell biology↗

bioRxiv2022

Dynamic Sex Differences in Reactive and Appetitive Aggression

Aggression is an evolutionarily conserved, adaptive component of social behavior. Studies in male mice illustrate that aggression is influenced by numerous factors including the degree to which an individual finds aggression rewarding and will work for access to attack and subordinate mice. While such studies have expanded our understanding of the molecular and circuit mechanisms of male aggression very little is known about female aggression, owed in part to limited availability of valid mouse models in females. Here we use an ethologically relevant model of male vs. female aggression by pair housing adult male and female outbred CFW mice with opposite sex cage mates. We assess reactive (defensive) aggression in the resident intruder (RI) test and appetitive (rewarding) aggression in the aggression conditioned place preference (CPP) and operant self-administration (SA) tests. Our results show dramatic sex differences in both qualitative and quantitative aspects of reactive vs. appetitive aggression. Males exhibit more wrestling and less investigative behavior during RI, find aggression rewarding and will work for access to a subordinate to attack. Females exhibit more bites, alternate between aggressive behaviors and investigative behaviors more readily during RI, however, they do not find aggression to be rewarding or reinforcing. These results establish sex differences in aggression in mice, providing an important resource for the field to better understand the circuit and molecular mechanisms of aggression in both sexes.

neuroscience↗

bioRxiv2022

Profilin 1 deficiency drives mitotic defects and impairs genome stability

Profilin 1 -encoded by PFN1- is a small actin-binding protein with a tumour suppressive role in various adenocarcinomas and pagetic osteosarcomas. However, its contribution to tumour development is not fully understood. Using fix and live cell imaging, we report that Profilin 1 inactivation results in multiple mitotic defects, manifested prominently by anaphase bridges, multipolar spindles, misaligned and lagging chromosomes, and cytokinesis failures. Accordingly, next-generation sequencing technologies highlighted that Profilin 1 knock-out cells display extensive copy-number alterations, which are associated with complex genome rearrangements and chromothripsis events in primary pagetic osteosarcomas with Profilin 1 inactivation. Mechanistically, we show that Profilin 1 is recruited to the spindle midzone at anaphase, and its deficiency reduces the supply of actin filaments to the cleavage furrow during cytokinesis. The mitotic defects are also observed in mouse embryonic fibroblasts and mesenchymal cells deriving from a newly generated knock-in mouse model harbouring a Pfn1 loss-of-function mutation. Furthermore, nuclear atypia is also detected in histological sections of mutant femurs. Thus, our results indicate that Profilin 1 has a role in regulating cell division, and its inactivation triggers mitotic defects, one of the major mechanisms through which tumour cells acquire chromosomal instability.

cell biology↗

bioRxiv2021

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters

BackgroundCortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable clinical tool to investigate brain reactivity and effective connectivity. However, these invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain spatiotemporal properties of CCEPs, as well as their relationships with classic sensory evoked potentials. ObjectiveTo demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) are sensitive to changes in stimulation parameters and compensate for the limitations typical of invasive recordings. MethodsSEEG and hd-EEG activities were simultaneously recorded during SPES in drug-resistant epileptic patients (N=36). Changes in stimulation parameters encompassed physical (pulse intensity and width), geometrical (angle and position with respect to white/grey matter) and topological (stimulated cortical area) properties. Differences were assessed by measuring the overall responses and the amplitude of N1 and N2 components of the CCEPs, and by their spectral profiles. ResultsWhile invasive and non-invasive CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, hd-EEG responses to SPES reproduced basic features of responses to transcranial magnetic stimulation and showed a much larger amplitude as compared to typical sensory evoked potentials. ConclusionsThe present results show that macroscale hd-EEG recordings are exquisitely sensitive to variations in SPES parameters, including local changes in physical and geometrical stimulus properties, while providing valuable information about whole-brain dynamics. Moreover, the common reference space across subjects represented by hd-EEG may facilitate the construction of a perturbational atlas of effective connectivity. HighlightsO_LICCEPs recorded with hd-EEG and SEEG are correlated. C_LIO_LIhd-EEG recording is highly sensitive to changes in stimulation parameters. C_LIO_LIhd-EEG responses show higher amplitude responses with respect to non-invasive ones. C_LIO_LISimultaneous recordings provide a fixed observation point across subjects. C_LI

neuroscience↗

bioRxiv2021

The rt-TEP tool: real-time visualization of TMS-evoked potentials to maximize cortical activation and minimize artifacts

BackgroundThe impact of transcranial magnetic stimulation (TMS) on cortical neurons is currently hard to predict based on a priori biophysical and anatomical knowledge alone. This problem can hamper the reliability and reproducibility of protocols aimed at measuring electroencephalographic (EEG) responses to TMS. New MethodWe introduce and release a novel software tool to facilitate and standardize the acquisition of TMS-evoked potentials (TEPs). The tool, rt-TEP (real-time TEP), interfaces with different EEG amplifiers and offers a series of informative visualization modes to assess in real time the immediate impact of TMS on the underlying neuronal circuits. ResultsWe show that rt-TEP can be used to abolish or minimize magnetic and muscle artifacts contaminating the post-stimulus period thus affording a clear visualization and quantification of the amplitude of the early (<50 ms) EEG response after averaging a limited number of trials. This real-time readout can then be used to adjust TMS parameters (e.g. site, orientation, intensity) and experimental settings (e.g. loudness and/or spectral features of the noise masking) to ultimately maximize direct cortical effects over the undesired sensory effects of the coils discharge. Comparison with Existing MethodsThe ensemble of real-time visualization modes of rt-TEP are not implemented in any current commercial software and provide a key readout to titrate TMS parameters beyond the a priori information provided by anatomical models. ConclusionsReal-time optimization of stimulation parameters with rt-TEP can facilitate the acquisition of reliable TEPs with a high signal-to-noise ratio and improve the standardization and reproducibility of data collection across laboratories. HighlightsO_LIrt-TEP provides an immediate EEG readout to assess the quality of TEPs in real time C_LIO_LIrt-TEP interfaces with most commercial EEG systems C_LIO_LIInformative, real time visualization allows maximising the cortical impact of TMS while minimizing artifacts C_LIO_LIrt-TEP facilitates the acquisition of reliable TEPs with a high signal-to-noise ratio C_LI

neuroscience↗

bioRxiv2021

TAAC - TMS Adaptable Auditory Control: a universal tool to mask TMS click

BackgroundCoupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones. New methodHere we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab(R)-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains. ResultsWe showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click. Comparison with existing methodsHere, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines), lower SPLs with respect to standard noises. ConclusionsAt odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

neuroscience↗