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Human linguistic units are hierarchical, and our brain responds differently when processing linguistic units during sentence comprehension, especially when the modality of the received signal is different (auditory, visual, or audio-visual). However, it is unclear how the brain processes and integrates language information at different linguistic units (words, phrases, and sentences) provided simultaneously in audio and visual modalities. To address the issue, we presented participants with sequences of short Chinese sentences through auditory or visual or combined audio- visual modalities, while electroencephalographic responses were recorded. With a frequency tagging approach, we analyzed the neural representations of basic linguistic units (i.e., characters/monosyllabic words) and higher-level linguistic structures (i.e., phrases and sentences) across the three modalities separately. We found that audio-visual integration occurs at all linguistic units, and the brain areas involved in the integration varied across different linguistic levels. In particular, the integration of sentences activated the local left prefrontal area. Therefore, we used continuous theta-burst stimulation (cTBS) to verify that the left prefrontal cortex plays a vital role in the audio-visual integration of sentence information. Our findings suggest the advantage of bimodal language comprehension at hierarchical stages in language-related information processing and provide evidence for the causal role of the left prefrontal regions in processing information of audio-visual sentences.

Continuous theta-burst stimulation (cTBS) induces long-lasting inhibitory effects on cortical excitability. Although cTBS has been reported to modulate neural oscillations and functional connectivity, it is still unclear how cTBS affects brain dynamics that could be captured by the resting-sate EEG microstate sequences. This study aims to investigate how cTBS over the left motor cortex affects brain dynamics. We applied 40 s-long cTBS over the left motor cortex of 28 healthy participants. Before and in multi-sessions up to 90 min after cTBS, their performance in a Nine-Hole Peg Test (NHPT), that measures the hand dexterity, and resting state EEG were recorded. Resting-sate EEG data were clustered into four microstates (namely A, B, C, and D) using k-means clustering algorithms. cTBS-induced changes in NHPT performance, microstate dynamics and functional connectivity networks were comprehensively assessed. As compared with baseline, the completion time of NHPT became shorter immediately after cTBS, suggesting cTBS-induced motor function improvement. After cTBS, the topography of microstate B revealed a greater change compared with other three topographies. Importantly, cTBS-induced decrease in completion time of NHPT correlated with cTBS-induced decrease of the mean occurrence of microstate B. Functional connectivity analysis further revealed that cTBS led to an increase of the node efficiency at C4 electrode in microstate B. These results indicated the specific modulation of cTBS over the motor cortex on the dynamics of microstate B. This work provided the evidence of the association between B and motor function, and it also implies the modulation of cTBS over the motor network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11571-021-09726-6.

Objective: The extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non-Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. Methods: We assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. Results: Cerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. Conclusion: Non-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. Significance: The meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The occipital face area (OFA) is hierarchically one of the first stages of the face processing network. It has originally been thought to be involved in early, structural processing steps, but currently more and more studies challenge this view and propose that it also takes part in higher level face processing, such as identification and recognition. Here we tested whether the OFA is involved in the initial steps of recognition memory and plays a causal role in the differential processing of familiar and unfamiliar faces. We used an offline, inhibitory continuous theta-burst stimulation (cTBS) protocol over the right OFA and the vertex as control site. Electroencephalographic (EEG) recording of event-related potentials (ERPs), elicited by visually presented familiar (famous) and unfamiliar faces was performed before and after stimulation. We observed a difference in ERPs for famous and unfamiliar faces in a time-window corresponding to the N250 component. Importantly, this difference was significantly increased by cTBS of the right OFA, suggesting its causal role in the differential processing of familiar and unfamiliar faces. The enhancement occurred focally, at electrodes close to the right hemispheric cTBS site, as well as over similar occipito-temporal sites of the contralateral hemisphere. To the best of our knowledge, this is the first study showing the causal role of the rOFA in the differential processing of familiar and unfamiliar faces, using combined cTBS and EEG recording methods. These results are discussed with respect to the nature of familiar face representations, supported by an extensive, bilateral network.

Transcranial magnetic stimulation (TMS) is a technique used to treat different neurological disorders non-invasively. A pulsed current to a coil generates a magnetic field ( $B$ -field) which induces an electric field ( $E$ -field). Underlying biophysical effects of TMS are unclear. Therefore, animal experiments are needed; however, making small TMS coils suitable for mice is difficult and their field strengths are typically much lower than for human sized coils. Objectives/Hypothesis . We aimed to design and demonstrate a mouse-specific coil that can generate high and focused $E$ -field. Methods . We designed a tapered TMS coil of 50 turns of 0.2 mm diameter copper wire around a 5 mm diameter tapered powdered iron core and discharged a $220~\mu \text{F}$ capacitor at 50 V through it. We measured $B$ -field with a Hall probe and induced $E$ -field with a wire loop. We measured temperature rise with a thermocouple. We applied 1200 pulses of continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) to mouse brain slices and analyzed how spontaneous electrical activity changed. Results . The coil gave maximum $B$ -field of 685 mT at the base of the coil and 340 mT at 2 mm below the coil, and maximum $E$ -field 2 mm below the coil of approximately 10 V/m, at 50 V power supply, with a temperature increase of 20 °C after 1200 pulses of cTBS. We observed no changes in $B$ -field with heating. cTBS reduced frequency of spontaneous population events in mouse brain slices up to 20 min after stimulation and iTBS increased frequency up to 20 min after stimulation. No frequency changes occurred after 20 min. No changes in amplitude of spontaneous events were found. Conclusion . The design generated fields strong enough to modulate brain activity in vitro .

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal recordings and behavior. Guided by anatomical MRI, we recorded single-cell activity in parietal area PFG during passive fixation of real-world objects. Overall, we observed a pronounced, long-lasting and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons exhibiting periods of hyperexcitability during the recovery phase. We applied the same stimulation protocol during visually-guided grasping of objects, and observed a significant grasping impairment. These results provide the first experimental evidence on the effects of cTBS on single neurons in awake behaving monkeys.

Mind wandering is a mental state that is typically characterized as attention drifting away from external tasks to internal thoughts (i.e., task-unrelated thought). The goal of this project is to reduce the propensity to mind wandering using continuous theta burst stimulation (cTBS) over the left angular gyrus (AG). cTBS is an repetitive transcranial magnetic stimulation (rTMS) technique developed to create long-lasting inhibitory effects in the stimulated brain regions (Rounis & Huang, 2020). In an accelerated protocol participants will be stimulated three times in a single session. The target region is the left angular gyrus (AG), an area that is part of the default mode network. By using inhibitory cTBS over the AG, we aim to reduce the propensity to mind wander by reducing the activity of the DMN. The rationale for this approach is that the DMN is commonly shown to be more active during mind wandering (Christoff et al., 2009; Mason et al., 2007), and a reduction of its activity and/or functional connectivity can therefore be hypothesized to result in a decrease of MW. If this approach is effective, it should make the participants able to stay more on task and to direct their attention better to the primary task, and therefore reduce mind wandering frequency. The outcome variables for this study will be self-reported mind wandering, and two behavioral features related to mind wandering (behavioral variability and randomness in sequence response). These behavioral features will be captured using a finger-tapping random-sequence generation task developed in our group (FT-RSGT; Boayue, et al., 2020). We expect that self-reported mind wandering and the behavioral measures will differ depending on whether the person received a real or fake stimulation.

The dorsolateral prefrontal cortex (DLPFC) is activated when bilinguals switch between languages. Language switching can also elicit the N2 event-related potential (ERP). This ERP component appears to capture the cognitive control processes related to conflict monitoring, response selection and response inhibition. In the present study, continuous theta-burst stimulation (cTBS) was used to examine the role of the left DLPFC in bilingual language switching, using a picture-naming task. Participants in the study were 17 Afrikaans-English bilinguals. The picture-naming task consisted of non-switch and switch trials. On non-switch trials, participants named two consecutive pictures in the same language. On switch trials, participants named consecutive pictures in different languages (e.g., Afrikaans and then English). The participants completed three testing sessions. In each session, participants received either cTBS to the left DLPFC or the vertex, or sham stimulation, and then completed the picture-naming task. The results showed that following DLPFC stimulation, the N2 ERP was attenuated on switch trials compared to non-switch trials. Vertex or sham stimulation did not modulate the N2 ERP. cTBS did not affect language switching at the behavioural level. These results provide support for the role of the left DLPFC in the cognitive control processes underlying bilingual language switching. Furthermore, the study demonstrates that these processes can be modulated via non-invasive brain stimulation and the effects detected at the neural level.

Reactions between basal a 60 dislocations and 10 1 ¯ 2 coherent twin boundaries (CTBs) in a Mg alloy were studied with atomic resolution. Individual dislocation-CTB reactions produced steps with residual dislocations and multiple twinning dislocations (TDs) gliding away, consequently resulting in TB migration. Reactions between 10 1 ¯ 2 CTBs and low-angle grain boundaries composed of basal a 60 dislocations created either basal-prismatic/prismatic-basal interfaces or asymmetric tilt grain boundaries, depending on whether TDs gliding away or not. Not only the emission of TDs by dislocation-TB reactions may drive TB migration, but also the resultant steps or facets along TBs can act as TD sources to facilitate TB migration. Our results indicate that roughness or severe loss of local coherency induced by dislocation-TB reactions does not intrinsically impede TB migration in Mg alloys. Dislocation-TB reactions may provide another feasible strategy to improve the ductility of Mg alloys, in addition to other techniques like grain refinement and texture modification.

In everyday life, risky decision-making relies on multiple cognitive processes including sensitivity to reinforcers, exploration, learning, and forgetting. Neuroimaging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in exploration and risky decision-making, but the nature of its computations and its causal role remain uncertain. We provide evidence for the role of the DLPFC in value-independent, directed exploration on the Iowa Gambling Task (IGT) and we describe a new computational model to account for the competition of directed exploration and exploitation in guiding decisions. Forty-two healthy human participants were included in a right DLPFC, left DLPFC or sham stimulation groups using continuous theta-burst stimulation (cTBS). Immediately after cTBS, the IGT was completed. Computational modelling was used to account for exploration and exploitation with different combinations with value-based and sensitivity to reinforcers for each group. Applying cTBS to the left and right DLPFC selectively decreased directed exploration on the IGT compared to sham stimulation. Model-based analyses further indicated that the right (but not the left) DLPFC stimulation increased sensitivity to reinforcers, leading to avoidance of risky choices and promoting advantageous choices during the task. Although these findings are based on small sample sizes per group, they nevertheless elucidate the causal role of the right DLPFC in governing the exploration-exploitation tradeoff during decision-making in uncertain and ambiguous contexts.

First-principles calculations were performed to investigate the structures and energetics of coherent twin boundaries (CTBs) and glide twin boundaries (GTBs) in hexagonal close-packed (hcp) Ti. The formation mechanism of GTBs and their correlation with twin growth were fundamentally explored. Results suggested that GTBs can form from the gliding of CTBs, through their interaction with basal stacking fault. The gliding eventually restored the CTB structures by forming a pair of single-layer twinning disconnections. The pile-up of twinning disconnections should be responsible for the wide steps at twin boundaries as observed in high-resolution transmission electron microscopy, which can further promote twin growth. Possible effects of various alloying elements on pinning twin boundaries were also evaluated, to guide the strengthening design of Ti alloys.

Introduction: Theta-burst stimulation (TBS) is a safe non-invasive neurostimulation technique used to improve cognitive and neuropsychiatric impairments. Combined outcome evaluation using event-related potentials (ERPs) and neuropsychological tests may allow a more thorough assessment of TBS treatment efficacy; however, some mixed results have been found, and their use remains scarce. Our main objective was to evaluate whether a session of TBS to the left dorsolateral prefrontal cortex (DLPFC) can impact upon the performance of both neuropsychological and neurophysiological tests. Methods: This double-blind sham-controlled study involved 28 healthy adults, between 18 and 30 years. Volunteers were randomly allocated to receive excitatory (intermittent [iTBS]), inhibitory (continuous TBS [cTBS]) or sham stimulation on the left DLPFC. Subjects were evaluated using ERPs (auditory oddball paradigm P300) and neuropsychological tests (Trail making test [TMT] and Stroop test of words and colours [STWC]), using a pre-post stimulation protocol. Results: Inhibitory stimulation led to significantly delayed P300 peak latencies (p < 0.001), with no consistent change in N2P3 amplitudes. cTBS also significantly influenced the expected group performance in Stroop C and Stroop interference (p = 0.025) compared to the iTBS and sham groups. No significant results were found in TMT tests after TBS. Conclusion: Our results suggest that P300 and specific Stroop colour and words test parameters can be similarly influenced by the same TBS protocol. This emphasizes the importance of mixed evaluation using neuropsychological and neurophysiological resources in research associated with the use of transcranial magnetic stimulation and cognition.

Background Cell blocks are alternative preparations of fluid cytological specimens. They can be used for immunochemical studies as complementary tools or when other techniques (eg, immunocytochemistry, flow cytometry) are not available. Objectives We aimed to provide comparative morphologic, immunohistochemical, and technical features of agar-based cell blocks (ACBs) and cell tube blocks (CTBs) from cavitary effusions. Methods Agar-based cell blocks and CTBs were obtained from canine and feline effusions with neoplastic/atypical cells or with packed cell volumes ≥3%. Cellularity, RBC separation, and cellular features were evaluated on digitalized H&E slides with evaluators blinded to the method. The immunohistochemical intensity and nonspecific background were assessed on pan-cytokeratin and vimentin-stained slides. Overall yield was calculated, and morphologic and immunohistochemical features were compared among paired samples. Technical and cellular features were also described. Results Agar-based cell blocks and CTBs yielded evaluable sections in 100% (52/52) and 98% (51/52) of the cases, respectively. Cellularity and RBC separation scores were significantly higher in CTBs. Similar staining intensities were observed, and background staining was more frequently seen in pan-cytokeratin-stained ACBs. Only basic materials and equipment were required for both methods. Agar-based cell block preparations were more operator dependent and difficult to standardize, whereas CTBs were easier to prepare, but laboratory processing was more demanding. Conclusions Both methods can be used to produce good sections for immunohistochemistry staining with no significant differences. Cell tube blocks are beneficial for RBC-rich samples, and little additional training is required to prepare the blocks. Both types of cell blocks are reliable, cost-effective methods that could be introduced in diagnostic laboratories to further characterize canine and feline effusions.

Objective The main limitation of neuromodulation techniques is inter-subject variability. Combining theta-burst stimulation (TBS) with gamma-transcranial alternating current stimulation (γ-tACS) allows to shape cortical plasticity. However, it is unknown whether γ-tACS modifies TBS-induced response variability. In this study, we measured the inter-subject variability of TBS-γ tACS and controlled the effect of the Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism. Methods Intermittent TBS (iTBS)-sham tACS, iTBS-γ tACS, continuous TBS (cTBS)-sham tACS, and cTBS-γ tACS were applied in randomised sessions. Inter-subject variability was measured using grand average and clustering methods. TBS-γ tACS effects on motor evoked potentials (MEP) were compared between Val/Val and Met carriers. Results We found that γ-tACS boosted iTBS-induced MEP facilitation and cancelled cTBS-induced MEP depression. Grand average analysis showed that γ-tACS prominently increased the percentage of iTBS responders and cTBS non-responders. The clustering method demonstrated that TBS-γ tACS response varied between subjects, a phenomenon unrelated to the BDNF genotype. Conclusions Enhancing γ oscillations through tACS boosts iTBS-induced LTP-like plasticity and suppresses cTBS-induced LTD-like plasticity of the primary motor cortex in a reliable manner. The BDNF Val66Met polymorphism does not influence these effects. Significance Since γ-tACS significantly increases the number of iTBS responders, it may be used in clinical settings.

Motor memories become resistant to interference by the process of consolidation, which leads to long-term retention. Studies have shown involvement of the somatosensory cortex in motor learning-related plasticity, but not directly in motor memory consolidation. This Neuro Forum article reviews evidence from a continuous theta-burst transcranial magnetic stimulation (cTBS) study by Kumar and colleagues (Kumar N, Manning TF, Ostry DJ. PLoS Biol 17: e3000469, 2019) that demonstrates the role of somatosensory, rather than motor, cortex in human motor memory consolidation during implicit motor learning.

Background: 18F-fluorodeoxyglucose PET/CT is recommended as an optional study in the current NCCN Clinical Practice Guidelines in Oncology for Breast Cancer after CT of the chest, abdomen, and pelvis with contrast and bone scan (CTBS) in stage IIA–IIIC breast cancer. We evaluated our experience with the use of PET/CT in this setting before beginning primary systemic therapy (PST) prior to planned surgery. Methods: We performed medical record abstractions of all adult female patients with clinical stage IIA–IIIC breast cancer diagnosed at Montefiore Medical Center from January 1, 2014, through January 1, 2019, who underwent PET/CT before PST. We calculated the proportion of patients upstaged after PET/CT and examined the cost and radiation exposure associated with PET/CT compared with CTBS. Results: A total of 195 patients with 196 breast cancers (bilateral disease in 1 patient) met the study inclusion criteria and had PET/CT as the first imaging study before PST. The overall upstaging rate for regional nodal metastasis and/or distant metastasis was 37% (73/196), including 24% for stage IIA (9/38), 39% for stage IIB (31/79), 54% for stage IIIA (22/41), 27% for stage IIIB (8/30), and 37% for stage IIIC (3/8). The overall upstaging rate for distant metastasis was 14% (27/196), including 0% for stage IIA, 13% for stage IIB (10/79), 22% for stage IIIA (9/41), 17% for stage IIIB (5/30), and 37% for stage IIIC (3/8). Medicare reimbursement rates were $1,604.37 for PET/CT and $1,679.94 for CTBS. The radiation dose for PET/CT was 14 mSv versus 21 mSv for CTBS. Conclusions: Approximately 37% of patients with clinical stage IIA–IIIC breast cancer who underwent PET/CT before PST showed more extensive disease, including 23% with more extensive nodal metastasis and 14% with distant metastasis. Given its high detection rate, comparable cost, lower radiation dose, and greater convenience, PET/CT should be considered as an alternative to CTBS rather than “optional” after CTBS, especially in patients who require an efficient and expeditious workup before initiating PST.

We recently proposed a neurocognitive model of distancing-an emotion regulation tactic-with a focus on the lateral parietal cortex. Although this brain area has been implicated in both cognitive control and self-projection processes during distancing, fMRI work suggests that these processes may be dissociable here. This preregistered (NCT03698591) study tested the contribution of left temporoparietal junction (TPJ) to distancing using repetitive transcranial magnetic stimulation. We hypothesized that inhibiting left TPJ would decrease the efficiency of distancing but not distraction, another regulation tactic with similar cognitive control requirements, thus implicating this region in the self-projection processes unique to distancing. Active and sham continuous theta burst stimulation (cTBS) were applied to 30 healthy adults in a single-session crossover design. Tactic efficiency was measured using online reports of valence and effort. The stimulation target was established from the group TPJ fMRI activation peak in an independent sample using the same distancing task, and anatomical MRI scans were used for individual targeting. Analyses employed both repeated-measures ANOVA and analytic procedures tailored to crossover designs. Irrespective of cTBS, distancing led to greater decreases in negative valence over time relative to distraction, and distancing effort decreased over time while distraction effort remained stable. Exploratory analyses also revealed that active cTBS made distancing more effortful, but not distraction. Thus, left TPJ seems to support self-projection processes in distancing, and these processes may be facilitated by repeated use. These findings help to clarify the role of lateral parietal cortex in distancing and inform applications of distancing and distraction.

Objectives: The study was designed to investigate the effects of transcranial magnetic stimulation (TMS) over the dorsolateral prefrontal cortex (DLPFC) on emotional recognition among individuals differentiated on antisocial personality disorder (APD) symptoms. Methods: Participants (N = 93) received continuous theta burst stimulation (cTBS) under four conditions: real or sham cTBS over the left and right DLPFC. After stimulation, participants performed a dynamic face recognition task depicting fearful, happy, sad, and painful expressions. Results: Left and right DLPFC stimulation were followed by improved accuracy of happy and painful emotions compared to sham conditions. Participants receiving left stimulation were also better able to recognize sad expressions compared to the left sham condition. A three-way interaction between type of stimulation, emotion recognition, and APD groups suggested that the identified TMS effects on emotion recognition were only significant for individuals at elevated risk for APD symptoms. Conclusions: Findings suggest that DLPFC stimulation can lead to benefits in emotion recognition among individuals high on APD symptoms.

Although the cerebellum is not among the most renowned brain structures affected in Alzheimer`s disease (AD), recent evidence suggest that it undergoes degenerative changes during the course of the disease. A main neurophysiological feature of AD patients is the remarkable impairment of long term potentiation (LTP)-like cortical plasticity assessed in the primary motor cortex (M1) using theta burst stimulation (TBS) protocols. In healthy conditions, continuous (cTBS) and intermittent TBS (iTBS) of the cerebellum induce respectively long term depression (LTD)-like and LTP-like after effects in the contralateral M1. Here we aimed at examining the effects of cerebellar TBS on contralateral M1 excitability in a sample of 15 AD patients and 12 healthy age matched controls (HS). Motor evoked potentials (MEPs) were obtained in the contralateral M1 before and after cerebellar cTBS and iTBS protocols. As compared to HS, AD patients showed an impairment of LTP-like cortical plasticity mechanisms following cerebellar iTBS. No difference was observed for the cTBS protocol, in which both populations exhibited the expected LTD-like after effect. This study shows that mechanisms of cerebellar-cortical plasticity are impaired in AD. Given its role in high order cognitive functions, new potential therapeutic strategies could be built up in the future to modulate neural activity in the cerebellum in AD.

Background Through transcranial magnetic stimulation (TMS) it is possible to change cortical excitability of the visual cortex, and to influence binocular balance. The main goal of our study is to assess the effect of transcranial magnetic stimulation, specifically theta burst stimulation (TBS), in a group of amblyopic volunteers measuring several visual parameters: visual acuity, suppressive imbalance, and stereoacuity. Methods Thirteen volunteers aged 19 to 24 years, randomly split in 2 groups, underwent 1 session of continuous TBS, stimulating the right occipital lobe. The first group with 8 volunteers was exposed to active stimulation with cTBS, and the other group with 5 volunteers was exposed to placebo stimulation. Results Significant improvements in visual acuity, suppressive imbalance, and stereoacuity were found in the amblyopic eye after cTBS. The average value of amblyopia in visual acuity before stimulation was 0.32 ± 0.20 logMar and after cTBS was 0.19 ± 0.17 logMar. The mean value for the control group before placebo stimulation was 0.28 ± 0.17 and after placebo stimulation was 0.28 ± 0.16. The suppressive imbalance in the group of amblyope subjects stimulated before cTBS was 0.26 ± 0.18 and after was 0.12 ± 0.12; the suppressive imbalance of the control group before the placebo stimulation was 0.34 ± 0.37 and after was 0.32 ± 0.40. Conclusions Visual acuity, suppressive imbalance, and stereoacuity had significant enhancements compared with baseline after cTBS over the right occipital lobe in an ambliopic population.

Prior functional magnetic resonance imaging (fMRI) studies indicate that a core network of brain regions, including the hippocampus, is jointly recruited during episodic memory, episodic simulation, and divergent creative thinking. Because fMRI data are correlational, it is unknown whether activity increases in the hippocampus, and the core network more broadly, play a causal role in episodic simulation and divergent thinking. Here we employed fMRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of hippocampal brain networks impairs both episodic simulation and divergent thinking. For each of two TMS sessions, continuous θ-burst stimulation (cTBS) was applied to either a control site (vertex) or to a left angular gyrus target region. The target region was identified on the basis of a participant-specific resting-state functional connectivity analysis with a hippocampal seed region previously associated with memory, simulation, and divergent thinking. Following cTBS, participants underwent fMRI and performed a simulation, divergent thinking, and nonepisodic control task. cTBS to the target region reduced the number of episodic details produced for the simulation task and reduced idea production on divergent thinking. Performance in the control task did not statistically differ as a function of cTBS site. fMRI analyses revealed a selective and simultaneous reduction in hippocampal activity during episodic simulation and divergent thinking following cTBS to the angular gyrus versus vertex but not during the nonepisodic control task. Our findings provide evidence that hippocampal-targeted TMS can specifically modulate episodic simulation and divergent thinking, and suggest that the hippocampus is critical for these cognitive functions.

Objectives: To synthesise the existing literature investigating if acute aerobic exercise enhances the response to experimentally-induced neuroplasticity paradigms. Methods: A systematic search of electronic databases Medline, PsycInfo and Embase was undertaken on 26 April 2018 and updated on 17 May 2019. Studies were included if they involved a bout of aerobic exercise; prescribed a bout of rest as a control condition; utilized a non-invasive brain stimulation paradigm to induce neuroplasticity; used TMS to assess neuroplasticity outcomes; participants were healthy 18-65 year old males and females with no diagnosed neurological/psychological impairments. Results: Eight papers (containing 12 experiments) met inclusion criteria. All studies utilized cycling or treadmill exercise as their exercise modality, and exercise intensity ranged from low intensity continuous exercise to high-intensity interval exercise. Four neuroplasticity paradigms were employed including paired associative stimulation (PAS) (n = 3), continuous theta-burst stimulation (cTBS) (n = 2), intermittent theta-burst stimulation (iTBS) (n = 2) and transcranial direct current stimulation (n = 1). Aerobic exercise enhanced neuroplastic responses (compared to rest) in seven of the 12 experiments. Conclusions: This review provides emerging evidence that acute aerobic exercise can enhance the response to experimentally-induced neuroplasticity paradigms. However, there remains great variability in the study design and reporting of effects in these studies and thus a more standardized approach is encouraged to better understand the relationship between acute aerobic exercise and neuroplasticity. Future studies should consider optimizing intensity, paradigms and duration of both exercise and neuroplasticity paradigms employed. Refereed/Peer-reviewed

This study was planned to include 60 patients with alcohol use disorders to test the effect of cTBS intervention on alcohol use by random assignment to true or pseudo-stimulation, and to follow up 1 year after the end of the intervention to record their relapse rate. Multimodal MRI data were collected from patients before and after the intervention to explore the neural network underlying the onset of the intervention.

Background: Opoid use disorder (OUD) is a global illness and reduction in craving by repeatative Transcranial Magnetic Stimulation (RTMS) is one of its management approaches. Orbito-frontal Cortex is implicated in the several behavioral aspects of substance use including craving. Brain derived neurotrophic factor (BDNF) has a critical role in addictive properties of drugs of use. Previous studies have shown significant improvement in craving with RTMS and demonstrated alterations of serum BDNF levels in various substance dependent individual associated with craving. Aim: To examine the efficacy of continuous Theta Burst Stimulation RTMS (CTBS-RTMS) over the right OFC as an adjunct to Naltrexone in patients of OUD and its correlation with serum BDNF levels. Methods: Forty patients with OUD were recruited with purposive sampling. At the end of detoxification CTBS -RTMS was applied by dividing them into two equal groups as active and sham group using alternate allocation. Obsessive compulsive drug use scale (OCDUS) was applied and serum BDNF level was measured overtime till the end of CTBS-RTMS session. Data was analyzed by SPSS version 25. Results: Both groups had shown significant reduction in craving (OCDUS score) and serum BDNF from the baseline to 14th session of the RTMS. But there was no significant difference when compared between the two groups. Significant correlation was observed between serum BDNF levels overtime with different clinical variables in active group. Conclusion: The study adds to the literature in building an understanding of how rTMS could be used in reducing cravings for opioids.

More than a decade of neuroimaging and brain stimulation studies point to a crucial role for the right dorsolateral prefrontal cortex (rDLPFC) in prosocial behavior. The intuitive prosociality model postulates that the rDLPFC controls intuitive prosocial behavior, whereas the reflective model assumes that the rDLPFC controls selfish impulses during prosocial behavior. The intuitive prosociality model implies that the transient disruption of the rDLPFC should increase voluntary transfers in both dictator and generosity games. In contrast, the reflective model suggests that the transient disruption of the rDLPFC should decrease transfers in the dictator game, without affecting voluntary transfers in the generosity game, in which selfish motives are minimized. The aim of this paper was to compare predictions of the intuitive and reflective models using the classic dictator game and generosity game and continuous theta burst stimulation (cTBS). In this study, two groups of healthy participants (dictators) received either cTBS over the rDLPFC or right extrastriate visual areas. As shown by the results, the transient disruption of the rDLPFC significantly promoted prosocial motives in the dictator game only, particularly in the trials with the lowest dictator’s costs. These findings partially support the notion that the rDLPFC controls intuitive prosocial behavior.

Transcranial magnetic stimulation (TMS) is used in several FDA-approved treatments and, increasingly, to treat neurological disorders in off-label uses. However, the mechanism by which TMS causes physiological change is unclear, as are the origins of response variability in the general population. Ideally, objective in vivo biomarkers could shed light on these unknowns and eventually inform personalized interventions. Continuous theta burst stimulation (cTBS) is a form of TMS which has been observed to reduce motor evoked potentials (MEPs) for 60 minutes or longer post-stimulation, although the consistency of this effect and its mechanism continue to be under debate. Here, we use glutamate-weighted chemical exchange saturation transfer (gluCEST) magnetic resonance imaging (MRI) at ultra-high magnetic field (7T) to measure changes in glutamate concentration at the site of cTBS. We find that gluCEST signal in the ipsilateral hemisphere of the brain generally decreases in response to cTBS, whereas consistent changes were not detected in the contralateral or in subjects receiving a sham stimulation.One Sentence SummaryWe used glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) imaging to detect changes in glutamate contrast in the brains of young, healthy adults undergoing transcranial magnetic stimulation (TMS) to the motor cortex.

Contains fulltext : 216048pub.pdf (Publisher’s version ) (Open Access) While much progress has been made in how brain organization supports language function, the language network's ability to adapt to immediate disturbances by means of reorganization remains unclear. The aim of this study was to examine acute reorganizational changes in brain activity related to conceptual and lexical retrieval in unimpaired language production following transient disruption of the left middle temporal gyrus (MTG). In a randomized single-blind within-subject experiment, we recorded the electroencephalogram from 16 healthy participants during a context-driven picture-naming task. Prior to the task, the left MTG was perturbed with real continuous theta-burst stimulation (cTBS) or sham stimulation. During the task, participants read lead-in sentences creating a constraining (e.g., "The farmer milks the") or nonconstraining context (e.g., "The farmer buys the"). The last word was shown as a picture that participants had to name (e.g., "cow"). Replicating behavioral studies, participants were overall faster in naming pictures following a constraining relative to a nonconstraining context, but this effect did not differ between real and sham cTBS. In contrast, real cTBS increased overall error rates compared to sham cTBS. In line with previous studies, we observed a decrease in alpha-beta (8-24 Hz) oscillatory power for constraining relative to nonconstraining contexts over left temporal- parietal cortex after participants received sham cTBS. However, following real cTBS, this decrease extended toward left prefrontal regions associated with both domain-general and domain-specific control mechanisms. Our findings provide evidence that immediately after perturbing the left MTG, the lexical-semantic network is able to quickly reconfigure, also recruiting domain-general regions. 11 p.

Background Congenital tracheobronchial stenosis (CTBS) is a rare congenital condition characterized by complete cartilage rings covering varying lengths of the major airway. In this study, we reviewed the outcomes of patients with CTBS receiving surgical tracheoplasty in our institute. Methods We retrospectively analyzed the outcomes of consecutive patients with CTBS operated between 2006 and 2017 when extracorporeal membrane oxygenation (ECMO) was used perioperatively. Results In total, 11 patients (median follow-up period, 4.2 years; interquartile range, 1.6–5.4) were included. Seven were symptomatic in the neonatal period, 10 had cardiorespiratory anomalies, 7 required preoperative bronchoscopic balloon dilatation, and 1 required preoperative stent placement. Slide tracheoplasty (STP) was performed in 9 patients, and 2 underwent pericardial patch tracheoplasty. Seven patients required postoperative balloon dilatation, and 6 required postoperative stent placement. Early stenting provided immediate ventilatory improvement in all patients and facilitated successful extubation in a median of 4 days after stenting in 80% of the patients. Conclusions Under ECMO, severe CTBS could be successfully treated through a combination of tracheoplasty and bronchoscopic management. STP provided excellent results for solitary trachea stenosis with a minimum diameter of ≥ 3 mm. In selected patients, postoperative tracheobronchial stent placement was crucial in minimizing the ECMO duration and facilitating extubation. Level of Evidence IV

The final design of coil terminal boxes (CTBs) and superconducting feeders for the superconducting magnets of JT-60 super advanced (JT-60SA), which is the tokamak device being built in Japan, have been fixed. Because of the limited space in the torus building, five CTBs are distributed around the main cryostat. The CTBs have long horizontal ducts to place the high temperature superconductor current leads in a low magnetic field area. It is required for feeders that both flexibility for deformation of 30 mm, and stiffness for acceleration due to an earthquake of 3.92 m/s 2 (+self-weight of 9.8 m/s 2 ) vertically and 5.88 m/s 2 horizontally have to be guaranteed. The design of feeder shape and support structure have been optimized and confirmed by finite-element analysis to satisfy the above requirements. As for the feeder joint, compact tools are required because of the small working space in the horizontal duct of CTBs. Joint resistances were measured to verify the connection tools and procedure. Test results show that the joint resistance meets the requirement of 5 nΩ. In this paper, the final design of CTBs and in-cryostat current feeders for JT-60SA are described and the results of validation tests and analysis are also reported.

Functional connectivity (FC) is fundamental to brain function and has been implicated in many neuropsychological and neuropsychiatric disorders. It is then of great scientific and clinical interest to find a non-invasive approach to modulate FC. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulational tool that can affect the target region and remote brain areas. While the distributed effects of TMS are postulated to be through either structural or functional connectivity, an understudied but of great scientific interest question is whether TMS can change the FC between these regions. The purpose of this study was to address this question in normal healthy brain using TMS with continuous theta burst stimulation (cTBS) pulses, which are known to have long-lasting inhibition function. FC was calculated from resting state fMRI before and after real and control (SHAM) stimulation. Compared to SHAM, the repetitive TMS (rTMS) reduces FC between the cTBS target: the left dorsolateral prefrontal cortex (lDLPFC) and brain regions within the default mode network (DMN), proving the effects of rTMS on FC. The reduction of FC might be the results of the inhibitory effects of cTBS rTMS.

Transcranial magnetic stimulation (TMS) makes use of electromagnetic induction principle to induce electrical fields in the neuronal tissues and has an effect on neuromodulation. Theta burst stimulation (TBS) as a novel pattern of TMS has been shown to have advantages over conventional repetitive TMS (crTMS) in modulating brain cortical excitability. However, to date little is known about the potential of TBS of acupuncture point (acupoint) in modifying the brain activity. An acupoint is a specific point in the human body with nerve trunk and nerve ending through it, which is sensitive to various stimuli. In this paper, different-mode magnetic stimulations including crTMS, continuous TBS (cTBS), intermittent TBS (iTBS), and corresponding Sham iTBS were used to stimulate the Neiguan acupoint (PC6). Electroencephalogram characteristics induced by different-mode magnetic stimulations were compared to investigate whether the mode of magnetic stimulation of acupoint would impact stimulation effects. The results showed that iTBS of acupoint could induce a remarkable evoked potential of P80 component, activate more brain functional areas compared to crTMS, cTBS, and Sham stimulation, which suggested that iTBS of acupoint could induce a powerful brain response and produce a plastic reorganization of the cortical network. This paper proved that iTBS of acupoint with lower stimulation intensity and fewer stimulation pulses may be one more effective stimulation mode than crTMS, which may be clinically useful.

Hemispheric asymmetries play an important role in multiple cerebral functions. Asymmetries in prefrontal cortex (PFC) function have been suggested to regulate emotional processing in that right-hemispheric dominance biases towards negative affect, whereas left PFC dominance favors positive affect. This study used transcranial magnetic stimulation to test the causal role of prefrontal asymmetries in the processing of emotional stimuli. To experimentally induce hemispheric asymmetries, 21 healthy volunteers underwent two separate sessions of inhibitory continuous theta burst stimulation (cTBS) to the left versus right dorsolateral prefrontal cortex. Each stimulation was followed by magnetoencephalographic (MEG) recordings of event-related fields elicited by visually presented emotional words in a silent reading task and a subsequent behavioral emotion categorization task. The asymmetry manipulation influenced valence processing of words in early, mid-latency and late time intervals in right occipitotemporal and parietal brain regions. Left-sided cTBS (inducing right-hemispheric dominance) consistently resulted in enhanced brain responses to negative words, while right-sided cTBS (inducing left-hemispheric dominance) enhanced responses to positive words. On a behavioral level, right-hemispheric dominance resulted in more categorization matches of negative compared to positive words, while left-hemispheric dominance resulted in reverse effects. These results provide direct evidence that bottom-up valence processing is influenced by prefrontal hemispheric asymmetry.

Theories of emotion suggest a close relation of interoception and emotion. However, knowledge of underlying neuronal networks is still sparse. Repetitive transcranial magnetic stimulation (rTMS) is one neurostimulation method allowing causal conclusions between functions and brain regions via stimulation or inhibition of underlying brain structures. In this study, rTMS with a continuous theta burst stimulation (cTBS) protocol was used aiming for inhibition of important interoceptive network structures (frontotemporal insular network and right somatosensory cortices). Stimulation effects were investigated on interoceptive accuracy (IAc), emotional evaluation and neuronal correlates of emotional picture processing in 18 male participants. The main findings were an emotional flattening in subjective valences for affective stimuli after inhibition of the frontotemporal anterior insular network and of somatosensory cortices, being mirrored in visual evoked potentials as increased N2/decreased P3, indicating an initial orientation reaction followed by decreased attentional processing of positive stimuli. Moreover, cardiac and respiratory IAc were positively associated with P3 amplitudes and negatively related to positive valence ratings. Positive associations of decreases of cardiac/respiratory IAc with decreases of arousal ratings and decreases of P3 amplitudes for negative stimuli after inhibition of the frontotemporal insular network and after inhibition of somatosensory cortices allow the conclusion of a causal relationship between reduced activity in interoceptive network structures and blunted emotional processing of visual stimuli. Our results suggest that both arousal, and valence aspects of emotional processing are disturbed after inhibition of interoceptive network structures, confirming core assumptions of peripheral theories of emotions and models of interoceptive predictive coding.

Annealing twins often form in metals with a face centered cubic structure during thermal and mechanical processing. Here, we conducted molecular dynamic (MD) simulations for copper and aluminum to study the interaction processes between {1 1 1}1/2 dislocations and a three-dimensional annealing twin. Twin boundaries are characterized with Σ3{1 1 1} coherent twin boundaries (CTBs) and Σ3{1 1 2} incoherent twin boundaries (ITBs). MD results revealed that dislocation-ITB interactions affect slip transmission for a dislocation crossing CTBs, facilitating the nucleation of Lomer dislocation.

Attentive motion tracking deficits measured using multiple object tracking (MOT) tasks have been identified in a number of neurodevelopmental disorders such as amblyopia and autism. These deficits are often attributed to the abnormal development of high-level attentional networks. However, neuroimaging evidence from amblyopia suggests that reduced MOT performance can be explained by impaired function in motion-sensitive area MT+ alone. To test the hypothesis that a subtle disruption of MT+ function could cause MOT impairment, we assessed whether continuous theta burst stimulation (cTBS) of MT+ influenced MOT task accuracy in individuals with normal vision. The MOT stimulus consisted of four target and four distractor dots and was presented at ±10° eccentricity (right/left hemifield). fMRI-guided cTBS was applied to left MT+. Participants (n = 13, age: 27 ± 3) attended separate active and sham cTBS sessions where the MOT task was completed before, 5-min post- and 30-min post-cTBS. Active cTBS significantly impaired MOT task accuracy relative to baseline for the right (stimulated) hemifield 5-min (10 ± 2% reduction) and 30-min (14 ± 3% reduction) post-stimulation. No impairment occurred within the left (control) hemifield after active cTBS or for either hemifield after sham cTBS. These results highlight the importance of lower level motion processing for MOT, suggesting that a minor disruption of MT+ function alone is sufficient to cause a deficit in MOT performance.

Non-invasive brain stimulation is a useful tool to probe brain function and provide therapeutic treatments in disease. When applied to the right posterior parietal cortex (PPC) of healthy participants, it is possible to temporarily shift spatial attention and mimic symptoms of spatial neglect. However, the field of brain stimulation is plagued by issues of high response variability. The aim of this study was to investigate baseline functional connectivity as a predictor of response to an inhibitory brain stimulation paradigm applied to the right PPC. In fourteen healthy adults (9 female, aged 24.8 ± 4.0 years) we applied continuous theta burst stimulation (cTBS) to suppress activity in the right PPC. Resting state functional connectivity was quantified by recording electroencephalography and assessing phase consistency. Spatial attention was assessed before and after cTBS with the Landmark Task. Finally, known determinants of response to brain stimulation were controlled for to enable robust investigation of the influence of resting state connectivity on cTBS response. We observed significant inter-individual variability in the behavioral response to cTBS with 53.8% of participants demonstrating the expected rightward shift in spatial attention. Baseline high beta connectivity between the right PPC, dorsomedial pre-motor region and left temporal-parietal region was strongly associated with cTBS response (R2 = 0.51). Regression analysis combining known cTBS determinants (age, sex, motor threshold, physical activity, stress) found connectivity between the right PPC and left temporal-parietal region was the only significant variable (p = 0.011). These results suggest baseline resting state functional connectivity is a strong predictor of a shift in spatial attention following cTBS. Findings from this study help further understand the mechanism by which cTBS modifies cortical function and could be used to improve the reliability of brain stimulation protocols.

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS., Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

BackgroundThere is high variability in post-stroke aphasia severity and predicting recovery remains imprecise. Standard prognostics do not include neurophysiological indicators or genetic biomarkers of neuroplasticity, which may be critical sources of variability.ObjectiveTo evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF) contributes to variability in post-stroke language recovery, and to assess whether BDNF polymorphism interacts with neurophysiological indicators of neuroplasticity to improve estimates of aphasia severity.MethodsSaliva samples and motor-evoked potentials (MEPs) were collected from participants with chronic aphasia subsequent to left-hemisphere stroke. MEPs were collected prior to continuous theta burst stimulation (cTBS; index for cortical excitability) and 10 minutes following cTBS (index for stimulation-induced neuroplasticity) to the left primary motor cortex. Analyses assessed the extent to which BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to predict aphasia severity beyond established predictors.ResultsVal66Val carriers showed less aphasia severity than Met allele carriers, after controlling for lesion volume and time post-stroke. Furthermore, Val66Val carriers showed expected effects of age on aphasia severity, and positive associations between both cortical excitability and stimulation-induced neuroplasticity and severity. In contrast, Met allele carriers showed weaker effects of age and negative associations between cortical excitability, stimulation-induced neuroplasticity and aphasia severity.ConclusionsNeurophysiological indicators and genetic biomarkers of neuroplasticity improved ability to predict aphasia severity. Furthermore, BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to improve predictions. These findings provide novel insights into mechanisms of variability in stroke recovery and may improve aphasia prognostics.

Problem Cell-free fetal DNA (cffDNA) shed from the placenta can be detected in maternal blood and increases incrementally during gestation. Concentrations are further elevated with pregnancy complications. Specific activators of cffDNA release in such complications have not been identified. Here, we use trophoblast cells from early and term placenta to examine cffDNA release following apoptosis, infection, and sterile inflammatory stress. Method of study HTR8/SVneo cells were used to model first-trimester trophoblasts, and term cytotrophoblasts (CTBs) were isolated from placentae collected after uncomplicated deliveries. Trophoblasts were treated with varying concentrations of doxorubicin (DOX), lipopolysaccharide (LPS), or high-mobility group box protein 1 (HMGB1) for 18 h. Cells or supernatants were quantified for caspase-3/7 cleavage, pro-inflammatory cytokine secretion, and cffDNA release. Results Both HTR8/SVneo and CTBs underwent caspase-3/7 cleavage following DOX treatment, with HTR8/SVneo cells more sensitive to apoptosis than term CTBs. Apoptotic cells released more cffDNA in a dose-dependent manner. Treatment with LPS resulted in an increase in pro-inflammatory IL-6 release, particularly in term CTBs compared to early trophoblasts; however, LPS did not affect cffDNA release. Lastly, while neither cell released more TNF-α following stimulation with HMGB1, both HTR8/SVneo and CTBs released significantly more cffDNA in the presence of HMGB1. Conclusions These data show that apoptosis and sterile inflammation induced by DOX and HMGB1, respectively, cause an increase in cffDNA concentrations in both first-trimester and term trophoblasts. Understanding physiologic release of cffDNA during healthy and complicated pregnancy can identify new targets for the diagnosis and treatment of gestational complications.

Hypnotizability, one’s ability to experience cognitive, emotional, behavioral, and physical changes in response to suggestions in the context of hypnosis, is a highly stable trait associated with increased functional connectivity between the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). We conducted a preregistered, triple-blinded, randomized controlled trial to test the ability of continuous theta-burst stimulation (cTBS) over a personalized neuroimaging-based L-DLPFC target to temporarily enhance hypnotizability. We tested our hypothesis in 78 patients with fibromyalgia syndrome (FMS), a functional pain disorder for which hypnosis has consistently been shown to be beneficial as a nonpharmacological treatment option. Pre-to-post cTBS change in Hypnotic Induction Profile scores (HIP; a standardized measure of hypnotizability) was significantly greater in the Active versus Sham group. Our findings suggest a causal relationship between L-DLPFC and dACC function and hypnotizability. Dose-response optimization should be further examined to formalize guidelines for future clinical utilization.Trial registrationClinicalTrials.govNCT02969707

Human cognition is often biased. It is a fundamental question in psychology how cognitive bias is modulated in the human brain. Automatic action tendency is a typical cognitive bias. The dorsolateral prefrontal cortex (DLPFC) is a crucial area for processing various behavioral tasks. We investigated the functional role of DLPFC in the modulation of cognitive bias by testing the automatic action tendency during automatic and regulated behavioral tasks. Unilateral intermittent or continuous theta burst stimulation (excitatory iTBS or inhibitory cTBS) was used to manipulate the left or right DLPFC excitability and assess the changes in automatic action tendency during a manikin task. An approaching behavior with positive stimulus and avoiding behavior with negative stimulus were performed in an automatic task. An approaching behavior with negative stimulus and avoiding behavior with positive stimulus were performed in a regulated task. Reaction time was measured. We confirmed the automatic action tendency that reaction time for performing an automatic task was shorter than that for performing a regulated task. The automatic action tendency was enhanced after left DLPFC excitatory iTBS and was abolished after left DLPFC inhibitory cTBS stimulation. On the other hand, right DLPFC excitatory iTBS accelerated the avoiding behaviors and right DLPFC inhibitory cTBS accelerated approaching behaviors. The results suggest that left DLPFC modulates the automatic action tendency while the right DLPFC modulates the direction of behavioral tasks. We conclude that left DLPFC and right DLPFC are key nodes in modulating the cognitive bias while their functional roles are different.

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and as a foundation for further understanding CTB differentiation dynamics., Summary: The generation of a publicly available SWATH-MS global spectral library of human second-trimester primary villous cytotrophoblasts differentiating along an invasive pathway.

Objective. Heterogeneous clinical responses to treatment with non-invasive brain stimulation are commonly observed, making it necessary to determine personally optimized stimulation parameters. We investigated neuroimaging markers of effective brain targets of treatment with continuous theta burst stimulation (cTBS) in mal de débarquement syndrome (MdDS), a balance disorder of persistent oscillating vertigo previously shown to exhibit abnormal intrinsic functional connectivity. Approach. Twenty-four right-handed, cTBS-naive individuals with MdDS received single administrations of cTBS over one of three stimulation targets in randomized order. The optimal target was determined based on the assessment of acute changes after the administration of cTBS over each target. Repetitive cTBS sessions were delivered on three consecutive days with the optimal target chosen by the participant. Electroencephalography (EEG) was recorded at single-administration test sessions of cTBS. Simultaneous EEG and functional MRI data were acquired at baseline and after completion of 10–12 sessions. Network connectivity changes after single and repetitive stimulations of cTBS were analyzed. Main results. Using electrophysiological source imaging and a data-driven method, we identified network-level connectivity changes in EEG that correlated with symptom responses after completion of multiple sessions of cTBS. We further determined that connectivity changes demonstrated by EEG during test sessions of single administrations of cTBS were signatures that could predict optimal targets. Significance. Our findings demonstrate the effect of cTBS on resting state brain networks and suggest an imaging-based, closed-loop stimulation paradigm that can identify optimal targets during short-term test sessions of stimulation. ClinicalTrials.gov Identifier: NCT02470377.

Background Repetitive transcranial magnetic stimulation (rTMS) has been reported to treat muscle spasticity in post-stroke patients. The purpose of this study was to explore whether combined low-frequency rTMS (LF-rTMS) and cerebellar continuous theta burst stimulation (cTBS) could provide better relief than different modalities alone for muscle spasticity and limb dyskinesia in stroke patients. Methods This study recruited ninety stroke patients with hemiplegia, who were divided into LF-rTMS+cTBS group (n=30), LF-rTMS group (n=30) and cTBS group (three pulse bursts at 50 Hz, n=30). The LF-rTMS group received 1 Hz rTMS stimulation of the motor cortical (M1) region on the unaffected side of the brain, the cTBS group received cTBS stimulation to the cerebellar region, and the LF-rTMS+cTBS group received 2 stimuli as described above. Each group received 4 weeks of stimulation followed by rehabilitation. Muscle spasticity, motor function of limb and activity of daily living (ADL) were evaluated by modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) scores, respectively. Results The MAS score was markedly decreased, FMA and MBI scores were markedly increased in the three groups after therapy than before therapy. In addition, after therapy, LF-rTMS+cTBS group showed lower MAS score, higher FMA and MBI scores than the LF-rTMS group and cTBS group. Conclusion Muscle spasticity and limb dyskinesia of the three groups are all significantly improved after therapy. Combined LF-rTMS and cTBS treatment is more effective in improving muscle spasticity and limb dyskinesia of patients after stroke than LF-rTMS and cTBS treatment alone.

Sensory cortices are required for learning to discriminate complex stimuli that predict threat from those that predict safety in rodents. Yet, sensory cortices may not be needed to learn threat associations to simple stimuli. It is unknown whether these findings apply in humans. Here, we investigated the role of primary sensory cortex in discriminative threat conditioning with simple and complex somatosensory conditioned stimuli (CS) in healthy humans. Immediately before conditioning, participants received continuous theta-burst transcranial magnetic stimulation (cTBS) to primary somatosensory cortex either in the CS-contralateral or CS-ipsilateral hemisphere. After overnight consolidation, threat memory was attenuated in the contralateral compared to the ipsilateral group, as indicated by reduced startle eye-blink potentiation. There was no evidence for a difference between simple and complex stimuli, or that CS identification or conditioning was affected, suggesting a stronger effect of cTBS on consolidation than on initial stimulus processing. We propose that non-invasive stimulation of sensory cortex may provide a new avenue for interfering with threat memories in humans.

Previous studies have shown that visuospatial working memory (VSWM) plays a key role in the encoding and processing of visuospatial information. More importantly, there is evidence suggesting the role of frontal and parietal cortical areas in VSWM and especially, the influence of the frontal cortex in regulating goal-directed behavior. However, the functional role of the right dorsolateral prefrontal cortex (rDLPFC) in visuospatial working memory is still unclear. Here, we noninvasively modulated the rDLPFC activity using continuous theta-burst stimulation (cTBS), with the vertex as the control site. Our study aimed to investigate the effects of cTBS over rDLPFC on working memory task (2- and 4-back) performance. Working memory performance was assessed at the baseline and after stimulation. We observed that the working memory performance as measured by discriminability index was impaired after cTBS over rDLPFC in 2-back task, whereas 4-back task performance was not significantly affected. More so, there was no effect on performance after cTBS over the vertex, suggesting a functional role of rDLPFC in VSWM. Our findings demonstrate the involvement of the rDLPFC in VSWM as well as the load-dependent effect of working memory performance. Taken together, our work constitutes a useful addition to the literature and underscores the effectiveness and efficiency of noninvasive brain stimulation in modulating neuro-cognitive activity.

Aim: To evaluate the effects of a single session of non-invasive brain stimulation (NIBS) on postural balance. Introduction: The NIBS has been used widely in improving balance. However, the effect of a single session of NIBS on balance in healthy individuals has not been systemically reviewed. Methods: A systematic literature review and best evidence synthesis were conducted, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, to determine the effects of different NIBS techniques on balance function in healthy individuals. The methodological quality of included articles was assessed by the risk of bias, and the Downs and Black tool. Data were analyzed by using the best evidence synthesis. Thirty-five articles were included that used the following NIBS techniques: anodal transcranial direct current stimulation (a-tDCS), cathodal transcranial direct current stimulation (c-tDCS), continuous theta burst stimulation (cTBS), and repetitive transcranial magnetic stimulation (rTMS) on primary motor cortex (M1), supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), and cerebellum on balance. Results: Strong evidence showed that a-tDCS of M1, SMA improve balance in healthy participants, and the a-tDCS of DLPFC induces improvement only in dual task balance indices. Also, the findings indicate that cerebellar a-tDCS might significantly improve balance, if at least 10 min cerebellar a-tDCS with an intensity of ≥1 mA, over or maximum 1.5 cm below the inion, is used. Strong evidence showed that c-tDCS, cTBS, and rTMS are not effective on the balance. Conclusion: According to the results, the a-tDCS may be a useful technique to improve balance in healthy adults. Impact statement The strong evidence found in this review indicates that single-session, stand-alone application of anodal transcranial direct current stimulation on the cerebellum, primary motor cortex (M1), and supplementary motor area can improve balance in healthy individuals. Moreover, strong evidence suggests that cathodal transcranial direct current stimulation has an adverse effect on balance and must be avoided as a technique for the treatment of balance. These results can be used to improve balance in patients with neurological disorders, and healthy older adults with balance dysfunctions.

The establishment and function of the human placenta is dependent on specialized cells called trophoblasts. Progenitor cytotrophoblasts (CTBs) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTBs committed to the villous pathway fuse with neighboring CTBs forming the outer multinucleated syncytiotrophoblast layer (SCT), while CTBs committed to the extravillous pathway develop into multi-layered cell columns that anchor the placenta to uterine tissue. At distal column sites, column CTBs differentiate into invasive extravillous trophoblasts (EVT) that facilitate uterine remodeling of spiral arteries and modulate the maternal immune response to fetal antigen. Unfortunately, little is known about the cellular and molecular processes controlling human trophoblast stem cell maintenance and differentiation into these critical trophoblast sub-lineages. To address this, our laboratory established a single cell RNA sequencing (scRNA-seq) dataset from first trimester placentas to identify molecular programs and cell states important in trophoblast progenitor establishment, renewal, and differentiation. Using this dataset, eight distinct trophoblast states were identified, representing progenitor cytotrophoblasts, intermediate column CTBs, syncytiotrophoblast progenitors, and terminally differentiated EVT. Lineage trajectory analysis identified a CTB origin that was reproduced in human trophoblast stem cell organoids. Heightened expression of basal cell adhesion molecule (BCAM) defined this primitive state, where CTBs selected for high levels of surface BCAM expression generated larger clonally-derived organoids than did CTB counterparts expressing lower levels of BCAM. Together, this work resolves complex gene networks within human trophoblast progenitor cells, and identifies BCAM as marker that defines an up-stream progenitor origin. Summary Statement A trophoblast progenitor niche enriched in BCAM shows complex cell trajectory dynamics and gene signaling pathways