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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.

Background Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability despite their short duration and low number of stimuli. However, this assumption, and thus the experimental validity of studies using TBS, is challenged by recent work showing large inter- and intra-subject variability in response to TBS protocols. Objectives To date, the reproducibility of TBS effects in humans has been exclusively assessed with motor evoked potentials (MEPs), which provide an indirect and limited measure of cortical excitability. Here we combined TMS with electroencephalography (TMS-EEG) and report the first comprehensive investigation of (1) direct TMS-evoked cortical responses to intermittent (iTBS) and continuous TBS (cTBS) of the human motor cortex, and (2) reproducibility of both iTBS- and cTBS-induced cortical response modulation against a robust sham control across repeat visits with commonly used cortical responsivity metrics. Results We show that although single pulse TMS generates stable and reproducible cortical responses across visits, the modulatory effects of TBS vary substantially both between and within individuals. Overall, at the group level, most measures of the iTBS and cTBS-induced effects were not significantly different from sham-TBS. Most importantly, none of the significant TBS-induced effects observed in visit-1 were reproduced in visit-2. Conclusions Our findings suggest that the generally accepted mechanisms of TBS-induced neuromodulation, i.e. through changes in cortical excitability, may not be accurate. Future research is needed to determine the mechanisms underlying the established therapeutic effects of TBS in neuropsychiatry and examine reproducibility of TBS-induced neuromodulation through oscillatory response dynamics.

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.

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

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.

Background Theta burst stimulation (TBS) and quadripulse stimulation (QPS) are known to induce synaptic plasticity in humans. There have been no head-to-head comparisons of the efficacy and variability between TBS and QPS. Objective To compare the efficacy and interindividual variability between the original TBS and QPS protocols. We hypothesized that QPS would be more effective and less variable than TBS. Methods Forty-six healthy subjects participated in this study. Thirty subjects participated in the main comparison experiment, and the other sixteen subjects participated in the experiment to obtain natural variation in motor-evoked potentials. The facilitatory effects were compared between intermittent TBS (iTBS) and QPS5, and the inhibitory effects were compared between continuous TBS (cTBS) and QPS50. The motor-evoked potential amplitudes elicited by transcranial magnetic stimulation over the primary motor cortex were measured before the intervention and every 5 min after the intervention for 1 h. To investigate the interindividual variability, the responder/nonresponder/opposite-responder rates were also analyzed. Results The facilitatory effects of QPS5 were greater than those of iTBS, and the inhibitory effects of QPS50 were much stronger than those of cTBS. The responder rate of QPS was significantly higher than that of TBS. QPS had a smaller number of opposite responders than TBS. Conclusion QPS is more effective and stable for synaptic plasticity induction than TBS.

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.

Background Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. Objective/Hypothesis This study brought together over 60 TMS researchers to form the ‘Big TMS Data Collaboration’, and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. Methods 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. Results 430 healthy participants’ TBS data was pooled across 22 studies (mean age = 41.9; range = 17–82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. Conclusions This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

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.

Background Neuroimaging studies suggest that facial expression recognition is processed in the bilateral posterior superior temporal sulcus (pSTS). Our recent repetitive transcranial magnetic stimulation (rTMS) study demonstrates that the bilateral pSTS is causally involved in expression recognition, although involvement of the right pSTS is greater than involvement of the left pSTS. Objective /Hypothesis: In this study, we used a dual-site TMS to investigate whether the left pSTS is functionally connected to the right pSTS during expression recognition. We predicted that if this connection exists, simultaneous TMS disruption of the bilateral pSTS would impair expression recognition to a greater extent than unilateral stimulation of the right pSTS alone. Methods Participants attended two TMS sessions. In Session 1, participants performed an expression recognition task while rTMS was delivered to the face-sensitive right pSTS (experimental site), object-sensitive right lateral occipital complex (control site) or no rTMS was delivered (behavioural control). In Session 2, the same experimental design was used, except that continuous theta-burst stimulation (cTBS) was delivered to the left pSTS immediately before behavioural testing commenced. Session order was counter-balanced across participants. Results In Session 1, rTMS to the rpSTS impaired performance accuracy compared to the control conditions. Crucially in Session 2, the size of this impairment effect doubled after cTBS was delivered to the left pSTS. Conclusions Our results provide evidence for a causal functional connection between the left and right pSTS during expression recognition. In addition, this study further demonstrates the utility of the dual-site TMS for investigating causal functional links between brain regions., Highlights • Dual-site TMS was used to test causal functional connectivity between left and right pSTS during expression recognition. • rTMS impaired facial expression recognition when delivered to the right pSTS during a facial expression recognition task. • cTBS delivered to the left pSTS prior to the task doubled the impairment effect of rTMS to the right pSTS during the task. • The results demonstrate causal functional connectivity between the left and right pSTS during expression recognition. • The results also demonstrate the utility of dual-site TMS for investigating interregional causal functional connectivity.

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

Introduction The vergence oculomotor system possesses two robust adaptive mechanisms; a fast “dynamic” and a slow “tonic” system that are both vital for single, clear and comfortable binocular vision. The neural substrates underlying these vergence adaptive mechanisms in humans is unclear. Methods We investigated the role of the posterior cerebellum in convergence adaptation using inhibitory continuous theta-burst repetitive transcranial magnetic stimulation (cTBS) within a double-blind, sham controlled design while eye movements were recorded at 250hz via infrared oculography. Results In a preliminary experiment we validated our stimulation protocols by reproducing results from previous work on saccadic adaptation during the classic double-step adaptive shortening paradigm. Following this, across a series of three separate experiments we observed a clear dissociation in the effect of cTBS on convergence adaptation. Dynamic adaptation was substantially reduced while tonic adaptation was unaffected. Baseline dynamic fusional vergence response were also unaffected by stimulation. Conclusions These results indicate a differential role for the posterior cerebellum in the adaptive control of convergence eye movements and provide initial evidence that repetitive transcranial magnetic stimulation is a viable tool to investigate the neurophysiology of vergence control. The results are discussed in the context of the current models of implicit motor adaptation of vergence and their application to clinical populations and technology design in virtual and augmented head mounted display architectures. Significance statement The cerebellum plays a critical role in the adaptive control of motor systems. Vergence eye movements shift our gaze in depth allowing us to see in 3D and exhibit two distinct adaptive mechanisms that are engaged under a range of conditions including reading, wearing head-mounted displays and using a new spectacle prescription. It is unclear what role the cerebellum plays in these adaptive mechanisms. To answer this, we temporarily disrupted the function of the posterior cerebellum using non-invasive brain stimulation and report impairment of only one adaptive mechanism, providing evidence for neural compartmentalization. The results have implications for vergence control models and applications to comfort and experience studies in head-mounted displays and the rehabilitation of clinical populations exhibiting vergence dysfunctions.

When direct experience is unavailable, animals and humans can imagine or infer the future to guide decisions. Behavior based on direct experience versus inference may recruit partially distinct brain circuits. In rodents, the orbitofrontal cortex (OFC) contains neural signatures of inferred outcomes, and OFC is necessary for behavior that requires inference but not for responding driven by direct experience. In humans, OFC activity is also correlated with inferred outcomes, but it is unclear whether OFC activity is required for inference-based behavior. To test this, we used noninvasive network-based continuous theta burst stimulation (cTBS) in human subjects (male and female) to target lateral OFC networks in the context of a sensory preconditioning task that was designed to isolate inference-based behavior from responding that can be based on direct experience alone. We show that, relative to sham, cTBS targeting this network impairs reward-related behavior in conditions in which outcome expectations have to be mentally inferred. In contrast, OFC-targeted stimulation does not impair behavior that can be based on previously experienced stimulus–outcome associations. These findings suggest that activity in the targeted OFC network supports decision-making when outcomes have to be mentally simulated, providing converging cross-species evidence for a critical role of OFC in model-based but not model-free control of behavior.SIGNIFICANCE STATEMENTIt is widely accepted that the orbitofrontal cortex (OFC) is important for decision-making. However, it is less clear how exactly this region contributes to behavior. Here we test the hypothesis that the human OFC is only required for decision-making when future outcomes have to be mentally simulated, but not when direct experience with stimulus–outcome associations is available. We show that targeting OFC network activity in humans using network-based continuous theta burst stimulation selectively impairs behavior that requires inference but does not affect responding that can be based solely on direct experience. These results are in line with previous findings in animals and suggest a critical role for human OFC in model-based but not model-free behavior.

The study of the physiological effects underlying brain response to transcranial magnetic stimulation is important to understand its impact on neurorehabilitation. We aim to analyze the impact of a transcranial magnetic stimulation protocol, the continuous theta burst (cTBS), on human neurophysiology, particularly on contralateral motor rhythms. cTBS was applied in 20 subjects over the primary motor cortex. We recorded brain electrical activity pre- and post-cTBS with electroencephalography both at rest and while performing motor tasks, to evaluate changes in brain oscillatory patterns such as mu and beta rhythms. Moreover, we measured motor-evoked potentials before and after cTBS to assess its impact on brain's excitability. On the hemisphere contralateral to the protocol, we did observe a significant increase in mu (p = 0.027) and beta (p = 0.006) rhythms from pre- to post-cTBS, at the beginning of arm elevation. The topology of action planning and motor execution suggests that cTBS produced an inhibitory effect that propagated to the contralateral hemisphere, thereby precluding the expected/desired excitation for therapy purposes. This novel approach provides support for the notion that this protocol induces inhibitory changes in contralateral motor rhythms, by decreasing desynchronization, contradicting the ipsilateral inhibition vs. contralateral disinhibition hypothesis. Our results have implications for personalized cTBS usage as a rehabilitation intervention, suggesting that an unexpected propagation of inhibition can occur.

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.

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered.Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.