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Background: Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring., Objective: To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach., Methods: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses., Results: Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%., Significance: EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols., Competing Interests: Declaration of interest CJK holds equity in Alto Neuroscience, Inc. All other authors have nothing to disclose., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Objective: We currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability., Methods: This closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP)., Results: In 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach., Conclusions: Real-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP., Significance: Enhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response., Competing Interests: Declaration of Interest. CJK holds equity in Alto Neuroscience, Inc and is a consultant for Flow Neuroscience. All other authors have nothing to disclose.

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2  ng / kg  body weight  ( BW ) / day . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA's revision of the TDI for BPA., Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model., Discussion: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.

We currently lack a reliable method to probe cortical excitability noninvasively from the human dorsolateral prefrontal cortex (dlPFC). We recently found that the strength of early and local dlPFC transcranial magnetic stimulation (TMS)-evoked potentials (EL-TEPs) varied widely across dlPFC subregions. Despite these differences in response amplitude, reliability at each target is unknown. Here we quantified within-session reliability of dlPFC EL-TEPs after TMS to six left dlPFC subregions in 15 healthy subjects. We evaluated reliability (concordance correlation coefficient [CCC]) across targets, time windows, quantification methods, regions of interest, sensor- vs. source-space, and number of trials. On average, the medial target was most reliable (CCC = 0.78) and the most anterior target was least reliable (CCC = 0.24). However, all targets except the most anterior were reliable (CCC > 0.7) using at least one combination of the analytical parameters tested. Longer (20 to 60 ms) and later (30 to 60 ms) windows increased reliability compared to earlier and shorter windows. Reliable EL-TEPs (CCC up to 0.86) were observed using only 25 TMS trials at a medial dlPFC target. Overall, medial dlPFC targeting, wider windows, and peak-to-peak quantification improved reliability. With careful selection of target and analytic parameters, highly reliable EL-TEPs can be extracted from the dlPFC after only a small number of trials., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mind blanking is a mental state in which attention does not bring any perceptual input into conscious awareness. As this state is still largely unexplored, we suggest that a comprehensive understanding of mind blanking can be achieved through a multifaceted approach combining self-assessment methods, neuroimaging and neuromodulation. In this article, we explain how electroencephalography and transcranial magnetic stimulation could be combined to help determine whether mind blanking is associated with a lack of mental content or a lack of linguistically or conceptually determinable mental content. We also question whether mind blanking occurs spontaneously or intentionally and whether these two forms are instantiated by the same or different neural correlates., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Predictive and reactive behaviors represent two mutually exclusive strategies in a sensorimotor task. Predictive behavior consists in internally estimating timing and features of a target stimulus and relies on a cortical medial frontal system [superior frontal gyrus (SFG)]. Reactive behavior consists in waiting for actual perception of the target stimulus and relies on the lateral frontal cortex [inferior frontal gyrus (IFG)]. We investigated whether SFG-IFG connections by the frontal aslant tract (FAT) can mediate predictive/reactive interactions. In 19 healthy human volunteers, we applied online transcranial magnetic stimulation (TMS) to six spots along the medial and lateral terminations of the FAT, during the set period of a delayed reaction task. Such scenario can be solved using either predictive or reactive strategies. TMS increased the propensity toward reactive behavior if applied to a specific portion of the IFG and increased predictive behavior when applied to a specific SFG spot. The two active spots in the SFG and IFG were directly connected by a sub-bundle of FAT fibers as indicated by diffusion-weighted imaging (DWI) tractography. Since FAT connectivity identifies two distant cortical nodes with opposite functions, we propose that the FAT mediates mutually inhibitory interactions between SFG and IFG to implement a "winner takes all" decisional process. We hypothesize such role of the FAT to be domain-general, whenever competition occurs between internal predictive and external reactive behaviors. Finally, we also show that anatomic connectivity is a powerful factor to explain and predict the spatial distribution of brain stimulation effects. SIGNIFICANCE STATEMENT We interact with sensory cues adopting two main mutually-exclusive strategies: (1) trying to anticipate the occurrence of the cue or (2) waiting for the GO-signal to be manifest and react to it. Here, we showed, by using noninvasive brain stimulation [transcranial magnetic stimulation (TMS)], that two specific cortical regions in the superior frontal gyrus (SFG) and the inferior frontal gyrus (IFG) have opposite roles in facilitating a predictive or a reactive strategy. Importantly these two very distant regions but with highly interconnected functions are specifically connected by a small white matter bundle, which mediates the direct competition and exclusiveness between predictive and reactive strategies. More generally, implementing anatomic connectivity in TMS studies strongly reduces spatial noise., (Copyright © 2023 the authors.)

Background: Studies investigating obsessive-compulsive disorder from an ethological approach have highlighted a specific motor pattern of compulsive rituals with respect to corresponding ordinary behaviors. Particularly, compulsive motor profile is built through the repetition of acts, with prevalence of nonfunctional ones and redirection of attention to its basic structural units. These formal features would characterize ritual behavior throughout evolution, from nonhuman animals to human cultures. However, no study to date has investigated a possible relationship between such motor profile and underlying psychopathology. Therefore, the first objective of the study was to confirm previous findings on a larger sample size of obsessive patients; the second objective was to elucidate whether motor profile might be associated with obsessive-compulsive psychopathology and/or prepsychotic symptoms of schizophrenia., Methods: Twenty-one obsessive-compulsive outpatients provided a videotape of their rituals. An equal number of healthy controls, matched for sex and age, were registered for corresponding ordinary acts. Obsessive patients were administered the Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, and the Frankfurt Complaint Questionnaire., Results: The results of the present study confirm that ritual compulsions present a specific motor structure characterized by repetition of both functional and nonfunctional acts and their longer duration. Such a motor pattern is independent from obsessive-compulsive psychopathology, whereas it results specifically associated with prepsychotic symptoms of schizophrenia., Conclusions: We argue that this association may reflect the adaptive significance of ritual behavior across evolution, that is, its homeostatic function in conditions of unpredictability.

Noninvasive brain stimulation and neuroimaging have revolutionized human neuroscience with a multitude of applications, including diagnostic subtyping, treatment optimization, and relapse prediction. It is therefore particularly relevant to identify robust and clinically valuable brain biomarkers linking symptoms to their underlying neural mechanisms. Brain biomarkers must be reproducible (i.e., have internal reliability) across similar experiments within a laboratory and be generalizable (i.e., have external reliability) across experimental setups, laboratories, brain regions, and disease states. However, reliability (internal and external) is not alone sufficient; biomarkers also must have validity. Validity describes closeness to a true measure of the underlying neural signal or disease state. We propose that these metrics, reliability and validity, should be evaluated and optimized before any biomarker is used to inform treatment decisions. Here, we discuss these metrics with respect to causal brain connectivity biomarkers from coupling transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We discuss controversies around TMS-EEG stemming from the multiple large off-target components (noise) and relatively weak genuine brain responses (signal), as is unfortunately often the case in noninvasive human neuroscience. We review the current state of TMS-EEG recordings, which consist of a mix of reliable noise and unreliable signal. We describe methods for evaluating TMS-EEG biomarkers, including how to assess internal and external reliability across facilities, cognitive states, brain networks, and disorders and how to validate these biomarkers using invasive neural recordings or treatment response. We provide recommendations to increase reliability and validity, discuss lessons learned, and suggest future directions for the field., (Published by Elsevier Inc.)

Objective: Ethological models have highlighted a specific motor structure of compulsions in obsessive-compulsive disorder (OCD), based on the rigid repetitions of acts, and with the adaptive significance of facing unpredictable conditions. Such an evolutionary mechanism might explain the robust association between childhood traumatic experiences (CTEs) and OCD. However, a relationship between CTEs and the motor structure of compulsions has not been investigated yet. The first objective of the study was to confirm a specific motor structure of OCD compulsions with respect to control behaviors; the second objective was to assess a possible association between the motor structure of compulsions and CTEs severity., Method: Thirty-two OCD outpatients (13 female, M age = 44.50 years, SE = 19.71) and 27 healthy controls (10 female, M age test was used to compare the motor structure of behavior between the groups; Pearson's correlations to investigate associations between motor parameters and CTEs.SE = 16.20), matched for sex and age, provided a videotape of their compulsions and corresponding ordinary acts, respectively. Behavior was scored with the software "Observer." Participants were administered the Yale-Brown Obsessive Compulsive Scale and the Childhood Trauma Questionnaire. A dependent t test was used to compare the motor structure of behavior between the groups; Pearson's correlations to investigate associations between motor parameters and CTEs., Results: Compulsions showed a specific motor structure due to the repetition of functional and nonfunctional acts. CTEs severity was especially associated with the repetition of functional acts, independently from OCD severity., Conclusion: Our findings, in confirming a peculiar motor structure for OCD compulsions, hint for the first time at a link between CTEs and compulsive repetition of functional acts, which would represent a plastic developmental response to CTEs unpredictability. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Different hypotheses have flourished to explain the evolutionary paradox of schizophrenia. In this contribution, we sought to illustrate how, in the schizophrenia spectrum, the concept of embodiment may underpin the phylogenetic and developmental pathways linking sensorimotor processes, the origin of human language, and the construction of a basic sense of the self. In particular, according to an embodied model of language, we suggest that the reuse of basic sensorimotor loops for language, while enabling the development of fully symbolic thought, has pushed the human brain close to the threshold of a severe disruption of self-embodiment processes, which are at the core of schizophrenia psychopathology. We adopted an inter-disciplinary approach (psychopathology, neuroscience, developmental biology) within an evolutionary framework, to gain an integrated, multi-perspectival model on the origin of schizophrenia vulnerability. A maladaptive over-expression of evolutionary-developmental trajectories toward language at the expense of embodiment processes would have led to the evolutionary "trade-off" of a hyper-symbolic activity to the detriment of a disembodied self. Therefore, schizophrenia psychopathology might be the cost of long-term co-evolutive interactions between brain and language., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Worldwide neonatal mortality rate is still very high in many countries, with a sharp difference between developed and developing countries. The difference of interventions to be implemented for reducing neonatal mortality rate  in developing and developed countries will be discussed.

Abstract: In recent decades, psychiatry and the neurosciences have made little progress in terms of preventing, diagnosing, classifying, or treating mental disorders. Here we argue that the dilemma of psychiatry and the neurosciences is, in part, based on fundamental misconceptions about the human mind, including misdirected nature-nurture debates, the lack of definitional concepts of "normalcy," distinguishing defense from defect, disregarding life history theory, evolutionarily uninformed genetic and epigenetic research, the "disconnection" of the brain from the rest of the body, and lack of attention to actual behavior in real-world interactions. All these conceptual difficulties could potentially benefit from an approach that uses evolutionary theory to improve the understanding of causal mechanisms, gene-environment interaction, individual differences in behavioral ecology, interaction between the gut (and other organs) and the brain, as well as cross-cultural and across-species comparison. To foster this development would require reform of the curricula of medical schools., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Non-invasive pulmonary surfactant (SF) administration for neonatal respiratory distress syndrome (NRDS) is a development of administration of SF. Administration of SF via a supraglottic device (SGD) has been shown to be effective. Here the results of administration of SF in NRDS in infants requiring oxygen and nasal-CPAP (n-CPAP) via two types of SGDs, LMA® vs iGel®, in a second level Neonatal Unit are reported in a retrospective study. Results - Fourteen infants in the LMA®Group were matched with 21 comparable infants in the iGel® Group (g.a. ≥30 wks and b.w. ≥ 1,500 gr) presenting NRDS with fraction of inspired oxygen (FiO2) ≥ 0.25 - 0.6, requiring n-CPAP. All infants presented a significant improvement of PaO2/FiO2 ratio that was seen earlier in the iGel® Group vs the LMA® Group. There was no severe adverse effect during the maneuver with both SGDs. No baby died, No.2 required endotracheal intubation for a second dose of SF as by protocol, and No. 1 was transferred to a higher level of care. Conclusion - Non-invasive SF administration via SGD has been done effectively at a second level Neonatal Unit and very early in the course of the disease therefore limiting transfer of the baby without complications with both SGDs. Improvement in gas exchange was more rapid in the iGel®Group. This result needs confirmation. In our experience iGel® was easier to use than LMA®.

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re-identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user-friendly 3D Slicer plugin-in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state-of-the-art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re-identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user-friendly interface, multiple input-output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)