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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.)

Background: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli., Objective: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential., Methods: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures., Results: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans., Conclusions: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans., Competing Interests: Declarations of competing interest None of the authors have conflicts of interest to disclose in relationship with the current work., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia., Methods: We prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement., Results: CCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts., Conclusion: For the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus., Significance: This intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Bisphenol A (BPA) is a widespread estrogenic chemical used in the production of polycarbonate, and epoxy resins lining food and beverage cans and in dental sealants. During fetal life the intrauterine environment is critical for the normal development, and even small changes in the levels of hormones, such as estradiol or estrogen-mimicking chemicals, can lead to changes in brain function and consequently in behavior. We review here a series of ethological studies on the effects of maternal oral exposure during the last part of gestation (prenatal exposure) or from gestation day 11 to postnatal day 7 (perinatal exposure) to a low, environmentally relevant dose of BPA (10 microg/kg bw/day) on behavioral responses of CD-1 mouse offspring. We examined both male and female offspring and found that maternal exposure to BPA affected: (1) behavioral responses to novelty before puberty and, as adults; (2) exploration and activity in a free-exploratory open field; (3) exploration in the elevated plus maze and (4) sensitivity to amphetamine-induced reward in the conditioned place preference test. A consistent effect of the maternal exposure to BPA is that in all these different experimental settings, while a significant sex difference was observed in the control group, exposure to BPA decreased or eliminated the sex difference in behavior. In addition, exposure of female mice to BPA in both adulthood or during fetal life altered subsequent maternal behavior. These findings, together with those from other laboratories, are evidence of long-term consequences of maternal exposure to low-dose BPA at the level of neurobehavioral development.

Exposure to estrogenic chemicals during critical periods in fetal life can alter the development of reproductive organs, the neuroendocrine system, and subsequent behavior. We examined the effects of prenatal exposure to the estrogenic chemicals, o,p'-DDT (the estrogenic contaminant in commercial DDT) and the drug diethystilbestrol (DES), as a positive control, on different forms of aggressive behavior in both male and female house mice. We also examined effects of these chemicals on male reproductive organs. From gestation days 11-17 female mice were fed an average concentration (dissolved in oil) 0.018 and 0.18 ng/g body weight of DES. Doses of o,p'-DDT were 18 and 180 ng/g body weight, based on the prediction that the in vivo potency of o,p'-DDT would be approximately 1000-times lower than DES. We found that prenatal exposure to DES increased the frequency of both males and females that responded aggressively to a same-sex conspecific. Preputial glands in males exposed to the 0.018 ng/g dose of DES were significantly enlarged relative to controls. Males exposed to the 18 ng/g dose of DDT had smaller testes than controls. The possible implications of perturbing the development of social behaviors, such as aggression, on individuals reproductive success and social structure of the population are discussed.

Lactating mice respond differentially to intruders of differing sex, displaying defensive attack against the male and offensive attack against the female. Such a phenotypic dichotomy appears to have adaptive value in that unfamiliar males pose a much greater threat to the offspring than do females. The present study examined the effects of the benzodiazepine anxiolytic chlordiazepoxide (CDP) (2.5-10.0 mg/kg) on this differential response pattern in aggression-naive (nonscreened) (NS) and aggression-experienced (screened) (S) lactating female mice (Mus musculus domesticus) confronting intruders of either sex in a 10-min test. This procedure was used to evaluate the influence of both the type of opponent and previous aggressive experience on basal behavioural profiles and drug action. Results showed that both intruder sex and prior screening for attack modulated the behaviour of lactating females toward intruders. In turn, both variables strongly influenced CDP effects on maternal aggression. In particular, in S dams, CDP dose-dependently increased maternal attack against males but decreased attack against female intruders. Conversely, in NS dams, CDP decreased attack (and fear) against males but did not affect it against females. In both S and NS conditions, CDP modified the attack strategy of lactating females against the male, switching it from a defensive to an offensive pattern. Exploration, social investigation, eating, and immobility were differentially affected by the drug treatment, depending on screening and/or intruder sex condition. These differential effects of CDP between S and NS conditions, toward either male or female intruders, cannot be fully explained by differences in the baseline levels of these behaviours. Alternative hypotheses are discussed. These findings demonstrate that the effects of CDP on maternal attack behaviour depend on not only the drug but also the object of attack, and hence the function of attack and the prior experience of the attacker.

Numerous chemicals released into the environment by man are able to disrupt the functioning of the endocrine system by binding to estrogen receptors in estrogen-responsive cells. The ability of o,p'-dichlorodiphenyl trichloroethane (DDT) and methoxychlor to compete with estradiol for binding to estrogen receptors in MCF-7 cells (relative binding affinity; RBA) was examined in both serum-free medium and 100% serum; this is referred to as a relative binding affinity-serum modified access (RBA-SMA) assay. RBA's ranged from 0.04% for o,p'-DDT (which showed enhanced access to cells in serum relative to serum-free medium) to 0.004% for methoxychlor (which did not show enhanced access in serum). Based on these findings, these pesticides, along with diethylstilbestrol (DES) as a positive control, were fed to pregnant mice from days 11-17 of pregnancy. When the male offspring were examined in adulthood for their rate of urine marking in a novel territory (territorial behaviour), the rate of urine marking increased dramatically with low doses of DES (relative to controls) and then decreased significantly at the highest dose administered prenatally. Relative binding in MCF-7 cells accurately predicted the doses of o,p'-DDT and methoxychlor that produced the same results, providing support for the hypothesis that effects on behaviour were mediated by binding to estrogen receptors in the developing brain.