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The impact of tumor focality on prostate cancer (PCa) prognosis has been addressed in several studies with conflicting results. Tumor foci from multifocal (MF) PCa can show highly heterogeneous molecular features. Our aim was to analyze the protein expression of PTEN, SPOP, SLC45A3, ETV1, ERG and the "triple hit" (ERG overexpression, PTEN plus SLC45A3 loss) in unifocal (UF) and MF PCa, to evaluate their value as prognostic markers according to focality, and the role of tumor heterogeneity in MF disease. PTEN, SPOP, SLC45A3, ETV1 and ERG immunohistochemical expression was evaluated in 185 PCa from 9 TMAs, 51 UF and 134 MF. In a subset of 69 MF cases, the dominant and secondary foci (DF and SF) were compared. Heterogeneity was considered when both tumor foci presented different expression patterns. Relationship with clinicopathological features was also analyzed. MF PCa was diagnosed in significantly younger patients when compared to UF ones (p = 0.007). ETV1 overexpression was associated with UF disease (p = 0.028). A shorter time to PSA recurrence was related to SLC45A3 wt expression in UF PCa (p = 0.052), and to SPOP expression loss (p = 0.043) or "triple hit" phenotype in MF PCa (p = 0.041). In MF cases, PTEN loss, SLC45A3 loss and "triple hit" phenotype were associated with the DF and had significant heterogeneity. In conclusion, our results indicate that UF and MF PCa have relevant and consistent molecular differences. The analysis of an immunohistochemical panel, composed by PTEN, SPOP, SLC45A3, ETV1 and ERG, could be useful to predict outcome in MF cases. [ABSTRACT FROM AUTHOR]

• Skin-cerebellum distance is the dominant factor determining cerebellar tDCS-induced electric field strength in healthy adults. • Interindividual differences in posterior fossa morphometry add unique explanatory variance to skin-cerebellum distance. • When targeting the midline cerebellum, field strength and focality differ between cephalic and extracephalic electrode montages. Clinical, behavioural, and neurophysiological effects of cerebellar transcranial direct current stimulation (tDCS) are highly variable and difficult to predict. We aimed to examine associations between cerebellar tDCS-induced electric field strength, morphometric posterior fossa parameters, and skin-cerebellum distance. As a secondary objective, field characteristics were compared between cephalic and extracephalic electrode configurations. Electric field simulations of midline cerebellar tDCS (7 × 5 cm electrodes, current intensities of 2 mA) were performed on MRI-based head models from 37 healthy adults using buccinator, frontopolar, and lower neck reference electrodes. Average field strengths were determined in eight regions of interest (ROIs) covering the anterior and posterior vermis and cerebellar hemispheres. Besides skin-cerebellum distance, various angles were measured between posterior fossa structures. Multivariable linear regression models were used to identify predictors of field strength in different ROIs. Skin-cerebellum distance and "pons angle" were independently associated with field strength in the anterior and posterior vermis. "Cerebellar angle" and skin-cerebellum distance affected field strength in anterior and posterior regions of the right cerebellar hemisphere. Field strengths in all examined cerebellar areas were highest in the frontopolar and lowest in the lower neck montage, while the opposite was found for field focality. The lower neck montage induced considerably less spreading toward anterior cerebellar regions compared with the buccinator and frontopolar montages, which resulted in a more evenly distributed field within the cerebellum. In addition to skin-cerebellum distance, interindividual differences in posterior fossa morphometry, specifically pons and cerebellar angle, explain part of the variability in cerebellar tDCS-induced electric field strength. Furthermore, when targeting the midline cerebellum with tDCS, an extracephalic reference electrode is associated with lower field strengths and higher field focality than cephalic montages. This study identifies two novel subject-specific anatomical factors that partly determine cerebellar tDCS-induced electric field strength and reveals differences in field characteristics between electrode montages. [ABSTRACT FROM AUTHOR]

Prospective Memory (PM) entails a set of executive processes primarily associated with the activation of frontal and parietal regions. Both the number of PM-targets to be monitored (i.e. task load) and the relationship between the type of PM-targets and the ongoing (ONG) task (i.e. task focality) can impact executive monitoring and PM performance. In the present imaging study, we manipulated load and focality of an event-based PM task to test the hypothesis that common resources engage in situations requiring high levels of cognitive control: that is, in high-load (i.e. monitor multiple PM-targets) and non-focal conditions (i.e. monitor at the same time letters' identity and color). We investigated monitoring-related and detection-related processes by assessing behavior and brain activity separately for ONG trials (monitoring) and PM-targets (detection). At the behavioral level, we found a significant interaction between load and focality during detection, with slowest reaction times for focal, high-load PM-targets. The imaging analyses of the detection phase revealed the activation of the left intraparietal sulcus in the high-load conditions. Both in the monitoring and the detection phases, we found overlapping effects of non-focality and low-load in the fusiform gyrus. Our results suggest that under low-load conditions, cognitive control operates via early selection mechanisms in the ventral occipito-temporal cortex. By contrast, high-load conditions entail control at later processing stages within the dorsal parietal cortex. We conclude that load and focality operate via different mechanisms, with the level of task load largely determining how cognitive control selects the most relevant information. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation is an electromagnetic induction-based non-invasive therapeutic technique for neurological diseases. For finding new clinical applications and enhancing the efficacy of TMS in existing neurological disorders, the current study focuses on a deep learning-based prediction model as an alternative to time-consuming electromagnetic (EM) simulation software. The main bottleneck of the existing prediction models is to consider very few input parameters of a standard coil such as coil type and coil position for predicting an output of electric field value. To overcome this limitation, a transformer-based prediction model titled as ViTab transformer is developed in this work to predict electric field (E-max), focality or area of stmulation (S-half), and volume of stimulation (V-half) by considering several input parameters such as sources of MRI images, types of coils, coil position, rate of change of current, brain tissues conductivity, and coil distance from the scalp. The proposed framework consists of a vision and a tab transformer to handle both image and tabular-type data. The prediction performance of the offered model is evaluated in terms of coefficient determination, R2 score, for E-max, V-half, and S-half in the testing phase. The obtained result in terms of R2 score for E-max, V-half, and S-half are found 0.97, 0.87, and 0.90 respectively. The results indicate that the suggested ViTab transformer model can predict electric field as well as focality more accurately than the current state-of-the-art methods. The reduced computational time, as well as efficient prediction accuracy, resembles that ViTab transformer can assist the neuroscientist and neurosurgeon prior to providing superior TMS treatment in near future.

We examined the influence of prospective memory (PM) cue focality in a sample of preschool children. Prior investigations in older populations indicated that focal targets were associated with enhanced PM performance, perhaps through more automatic retrieval processes. Importantly, this influential variable has not been thoroughly explored in younger samples. Over three test sessions, preschool children completed a memory task where they were shown a series of animals. During retrieval, participants were shown all of the animals except for one, and they had to name the missing animal. While engaged in this task, participants in the focal PM condition were instructed to remove particular animals (e.g., spider) from the game if they saw them. In the nonfocal condition, participants were told to remove any animal that was entirely one color (e.g., black) if they saw them during the game. The results demonstrated no difference in PM remembering between focal and nonfocal conditions. These results suggest that the effects of focality may not be present at the beginning stages of PM development. The implications for PM retrieval processes also are discussed. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non-invasive neurom odulation technique used to treat various neurological disorders, including major depression. Since the cerebellum is a complex structure connected almost throughout the central nervous system, TMS has gained popularity in the field of cerebellar neurostimulation and promises to stimulate cerebellar activity non-invasively. The TMS coil structure and material play significant roles in achieving the focality of the coil. However, few studies have proposed various structures of solid coils, such as figure-of-eight (FOE) and butterfly-shaped coils to increase the focality of the coil. However, it is observed that there is always a trade-off between the field intensity and the temperature of the coil. In this study, new designs of TMS coils were proposed to reduce the temperature of the coil without significantly reducing the magnetic field intensity. Finite-element simulation tools such as ANSYS Maxwell® and FEMTET® were used to simulate the field intensity and thermal analysis. The proposed design included hollow coils, double-layered hollow coils, and enamel-layered hollow coils. [ABSTRACT FROM AUTHOR]

Although approximately 10%–15% of patients with idiopathic generalized epilepsy (IGE)/genetic generalized epilepsy remain drug‐resistant, there is no consensus or established concept regarding the underlying mechanisms and prevalence. This review summarizes the recent data and the current hypotheses on mechanisms that may contribute to drug‐resistant IGE. A literature search was conducted in PubMed and Embase for studies on mechanisms of drug resistance published since 1980. The literature shows neither consensus on the definition nor a widely accepted model to explain drug resistance in IGE or one of its subsyndromes. Large‐scale genetic studies have failed to identify distinct genetic causes or affected genes involved in pharmacokinetics. We found clinical and experimental evidence in support of four hypotheses: (1) "network hypothesis"—the degree of drug resistance in IGE reflects the severity of cortical network alterations, (2) "minor focal lesion in a predisposed brain hypothesis"—minor cortical lesions are important for drug resistance, (3) "interneuron hypothesis"—impaired functioning of γ‐aminobutyric acidergic interneurons contributes to drug resistance, and (4) "changes in drug kinetics"—genetically impaired kinetics of antiseizure medication (ASM) reduce the effectiveness of available ASMs. In summary, the exact definition and cause of drug resistance in IGE is unknown. However, published evidence suggests four different mechanisms that may warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Conventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality. Aim: To determine the regional volume parameters that differentiate the focal and non-focal groups. Methods: T1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.” Results: Regional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses. Conclusion: The CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL). [ABSTRACT FROM AUTHOR]

BackgroundConventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality.AimTo determine the regional volume parameters that differentiate the focal and non-focal groups.MethodsT1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.”ResultsRegional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses.ConclusionThe CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL).

We experimentally investigate, in an unstructured bargaining environment with commonly known money payoffs, the attraction effect and compromise effect (AE and CE) in bargaining, namely, a tendency for bargainers to agree to an intermediate option (CE) or to an option that dominates another option (AE). We conjecture that the relevance of the AE and CE in bargaining is constrained by how focal the feasible agreements' payoffs are. We indeed observe that there are significant AEs and CEs, but these effects are mediated by the efficiency and equality properties of the feasible agreements. Due to the allure of equality, the effects are harder to observe when an equal earnings contract is available. Decoys are more effective in shifting agreements from a very unequal contract to a less unequal one rather than the reverse. This paper was accepted by Yuval Rottenstreich, behavioral economics and decision analysis. [ABSTRACT FROM AUTHOR]

Background: Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. Methods: We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. Results: HCCs with 1, 2, or ≥ 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. Conclusions: MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) aggressiveness factors include serum levels of alpha-fetoprotein (AFP), maximum tumor diameter (MTD), tumor multifocality, and presence of portal vein thrombosis (PVT). Aims: The interdependence of these factors has not been closely studied. Methods: A large HCC database was examined for the presence of patients with PVT and multifocality and was analyzed retrospectively for the relationship of these 2 parameters to each other and to MTD and survival. Results: Multifocality was found to increase with increase in MTD in the whole cohort and especially in patients with PVT. PVT also increased with increasing MTD. Neither increases in multifocality nor in PVT depended on elevated serum AFP levels, although they each increased with higher AFP levels. PVT increased in monofocal tumors as MTD increased but increased further in multifocal tumors. Conclusions: Multifocality and PVT appear to be separate processes, each increasing with increase in MTD and AFP levels. The data support the hypothesis that in hepatocarcinogenesis, various factors cause increase in MTD, that in turn causes increased multifocality and PVT, which are non-co-dependent. However, both multifocality and PVT mechanisms involve both HCC cell growth and invasiveness, multifocality in liver parenchyma, and PVT in the portal vein. [ABSTRACT FROM AUTHOR]

Background: In transcranial direct current stimulation (TDCS), electric current is applied via two large electrodes to modulate brain activity. Computational models have shown that large electrodes produce diffuse electric fields (EFs) in the brain, which depends on individual head and brain anatomy. Recently, smaller electrodes as well as novel electrode arrangements, including high-definition TDCS (HD-TDCS) montages, have been introduced to improve the focality of EFs. Here, we investigated whether the EFs of focal montages are more susceptible to interindividual anatomical differences. Methods: Thirteen TDCS montages, including conventional M1-contralateral forehead montages with different stimulating electrode sizes as well as 4 × 1 HD and bipolar HD montages, producing varying EF focalities were modeled using the finite element method in 77 subjects, with individual anatomically realistic models based on magnetic resonance images. Results: Interindividual variability of predicted EFs increased with EF focality for conventional M1-contralateral forehead and 4 × 1 HD montages. 4 × 1 HD-TDCS was found to have the highest EF focality and greatest variability. Bipolar HD montages targeting the region between two small electrodes did not follow this pattern, but produced EF magnitudes comparable to those of 4× 1 HD-TDCS, with a minor decrease in focality and lower interindividual variability. Conclusions: EF focality in TDCS was achieved at the cost of increased interindividual variability. Hence, individual modeling is required to plan EF doses when focal montages are used. Among the studied montages, bipolar HD montages provided a compromise between inter-individual variability, focality and magnitude of the predicted EFs.

Aim: Experience of endoscopic submucosal dissection (ESD) for colorectal lesions in the setting of inflammatory bowel disease (IBD) remains limited. The aim of this work was to determine the safety, feasibility and oncological outcomes of ESD in patients with IBD. Method: A retrospective review of all adult patients (≥18 years) with a known diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) who underwent advanced colonoscopy and ESD between 1 January 2014 and 1 October 2020. Data collected included patient demographics, disease characteristics, pathological variables and procedure‐related complication rates. Results: A total of 25 patients were included: 19 (76%) were male with a median age of 63 years and disease duration of more than 10 years. Sixteen had UC and nine had CD; the majority were taking corticosteroids, immunomodulators or monoclonal antibodies at the time of ESD. The median procedure time was 41 min and the majority (n = 18; 72%) utilized chromoendoscopy. The median lesion size was 30 mm: eight had low‐grade dysplasia, nine had high‐grade dysplasia and three had adenocarcinoma and underwent oncological resection. None had surgical intervention for complication of ESD or perforation. A total of 23 (88%) had a complete R0 resection. Over a median follow‐up of 19 months, three were found to have dysplasia excised in polyps and none had subsequent adenocarcinoma. Conclusion: ESD in the setting of IBD is safe and effective for complete removal of large neoplastic lesions, allowing for ongoing endoscopic surveillance and organ preservation rather than surgical intervention. [ABSTRACT FROM AUTHOR]

Experimental data have indicated that transcranial magnetic stimulation (TMS) has high spatial specificity. For instance, even a millimeter-scale movement of the TMS coil above the motor cortex can change the recorded response in peripheral muscles drastically. However, such a small coil displacement induces a cortical electric field that overlaps considerably with the original electric field. Here, we describe how the basic electrophysiological properties of neurons can explain the apparent high spatial resolution of TMS. We show with simulations that a TMS intensity close to the neuronal threshold yields the highest spatial resolution, albeit with a possible tradeoff with the signal-to-noise ratio. The simulations suggest that with such a TMS intensity, the activated cortical area is significantly smaller than the area in which the electric field exceeds its half-maximum strength. [ABSTRACT FROM AUTHOR]

In transcranial direct current stimulation (TDCS), electric current is applied via two large electrodes to modulate brain activity. Computational models have shown that large electrodes produce diffuse electric fields (EFs) in the brain, which depends on individual head and brain anatomy. Recently, smaller electrodes as well as novel electrode arrangements, including high-definition TDCS (HD-TDCS) montages, have been introduced to improve the focality of EFs. Here, we investigated whether the EFs of focal montages are more susceptible to interindividual anatomical differences. Thirteen TDCS montages, including conventional M1-contralateral forehead montages with different stimulating electrode sizes as well as 4 × 1 HD and bipolar HD montages, producing varying EF focalities were modeled using the finite element method in 77 subjects, with individual anatomically realistic models based on magnetic resonance images. Interindividual variability of predicted EFs increased with EF focality for conventional M1-contralateral forehead and 4 × 1 HD montages. 4 × 1 HD-TDCS was found to have the highest EF focality and greatest variability. Bipolar HD montages targeting the region between two small electrodes did not follow this pattern, but produced EF magnitudes comparable to those of 4× 1 HD-TDCS, with a minor decrease in focality and lower interindividual variability. EF focality in TDCS was achieved at the cost of increased interindividual variability. Hence, individual modeling is required to plan EF doses when focal montages are used. Among the studied montages, bipolar HD montages provided a compromise between inter-individual variability, focality and magnitude of the predicted EFs. • TDCS focality increases carry a cost of increased interindividual variability. • More focal electric fields tend to have higher magnitudes with M1-SO TDCS. • Bipolar HD montages provide good control of electric fields. [ABSTRACT FROM AUTHOR]

Prospective memory (PM) refers to remembering to perform intended actions in the future. Older adults in particular have been shown to be negatively affected by PM tasks that require a high amount of attentional resources (i.e., nonfocal tasks). This age-related PM deficit has been attributed to reduced target monitoring in this age group older adults. However, this conclusion was based on indirect measures of monitoring, such as costs of the ongoing task. The present study set out to 1) investigate older adults' PM target monitoring by, for the first time, employing a direct measure (i.e., eye tracking), 2) assess differences in monitoring between PM tasks that differ in their focality, and 3) examine whether differences in PM monitoring can indeed explain older adults' reduced PM performance in nonfocal tasks. Results demonstrate that while older, but not younger adults, showed reduced performance in a nonfocal PM task, overt monitoring (eye movements) of these groups did not differ between focality conditions. Further analyses showed that older adults' performance was still reduced on the strategically more demanding task after controlling for overt target monitoring (i.e., including only trials in which the participant monitored). In contrast to indirect measures of cue monitoring, our findings illustrate that older adults' deficits on nonfocal PM tasks cannot (exclusively) be explained by reduced monitoring. Instead, processing that takes place after target monitoring are discussed as possible mechanisms underlying older adults' reduced PM performance in nonfocal tasks. • PM monitoring was investigated using eye tracking, in younger and older adults. • Older, but not younger adults' PM accuracy was reduced by a nonfocal PM task. • Monitoring proportions were very high and did not differ between tasks. • Older adults seem to not show a monitoring deficit in nonfocal PM tasks. • Post-monitoring processes might account for focality effects in older results. [ABSTRACT FROM AUTHOR]

Knowing the gender of a counterpart can be focal in the willingness to collaborate in team settings that resemble the classic coordination problem. This paper explores whether knowing a co-worker’s gender affects coordination on the mutually beneficial outcome in a socially risky environment. In an experimental setting, subjects play a one-shot stag hunt game framed as a collaborative task in which they can “work together” or “work alone.” We exogenously vary whether workers know the gender of their counterparts pre-play. When gender is revealed, female players tend to gravitate to collaboration and efficient coordination regardless of the knowledge. Males, when knowingly paired with another male, tend to collaborate less, and thus, are less likely to coordinate on the Pareto optimal outcome. These results demonstrate one way that gender focality can lead to inefficient outcomes and provide insight for organizations looking to induce collaboration among workers.

The role of metacognition in prospective memory (PM) has received relatively little attention. This study combined data from several experiments to identify the strategy repertoire employed during a classic laboratory PM task and to determine whether self-reported strategy was related to performance. Participants (N = 668) completed either a focal or nonfocal PM task embedded in an ongoing lexical decision task. The results indicated that participants reported the same strategy repertoire regardless of PM task focality. Participants who reported using a strategy performed better than those who did not report using one, and this was especially true under nonfocal conditions. Self-reported strategy use was also associated with more cost to the ongoing task when the opportunity to complete the PM task was present. These findings add to what is known about the metacognitive components of PM and underscore the need for additional research in this area. [ABSTRACT FROM AUTHOR]

Identifying the neurocognitive mechanisms that lead individuals remembering to execute an intention at the right moment (prospective memory, PM) and how such mechanisms are influenced by the features of that intention is a fundamental theoretical challenge. In particular, the functional contribution of subcortical regions to PM is still unknown. This study was aimed at investigating the role of the medial subdivision of the mediodorsal thalamic nucleus (mMDT) in PM, with particular focus on the processes that are mediated by the projections from/to this structure. We analysed the performance of a patient (OG) with a right‐sided lesion involving the mMDT in a series of PM tasks that varied for focality (i.e., overlapping of processes for the PM and ongoing tasks) and emotional valence of the stimuli, comparing the patient's performance with that of a control group. We found that the mMDT damage led to deficits in PM that were modulated by focality and emotional valence. OG indeed showed: a greater cost in the ongoing performance when a non‐focal PM task was added; a slowing down in retrieving the intentions, in particular when these were associated with focal PM cues; an abnormal performance in the task with positive PM cues. Our findings provide evidence of a contribution of mMDT to PM and suggest a modulation of prefrontal‐dependent strategic monitoring and a possible interaction with the limbic structures in the integration of emotion and PM processes. They also give support to the still controversial idea that connections with the perirhinal cortex mediate familiarity‐based recognition. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic value of positive surgical margins (PSM) focality for the prediction of biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP) for prostate cancer. Methods: All men with clinically localized prostate cancer undergoing RARP in our tertiary referral centre between May 2005 and August 2016 were retrospectively identified. Patients with neoadjuvant therapy were excluded. Comparisons were made between cases with negative surgical margins (NSM), unifocal PSM (uPSM), and multifocal PSM (mPSM). Results: From a total of 973 patients available for analysis, 315 (32%) had a PSM. In these patients, 190 had uPSM and 125 had mPSM. Focality of PSM was significantly associated with tumour stage and grade, preoperative PSA, and postoperative PSA persistence (all p < 0.001), but not with nerve sparing (NS) (p = 0.15). PSA persistence was found in 120 (12%) patients, resulting in 853 patients available for survival analyses with a median follow-up of 52 months. Both uPSM and mPSM were found to be independent predictors of BCR, conferring a hazard ratio of 1.9 (95% CI 1.3–3.0; p = 0.002) and 3.4 (95% CI 2.1–5.6; p < 0.001), respectively, when compared to NSM. In subgroup analyses, PSM was particularly predictive for BCR when patients underwent unilateral or bilateral NS (p ≤ 0.003). Conclusions: Based on a large case series of RARP, we found PSM focality to be an independent predictor of BCR, with a 1.9- and 3.4-fold risk increase for BCR in case of uPSM and mPSM, respectively. PSM seems to be of particular prognostic relevance when NS has been performed. [ABSTRACT FROM AUTHOR]

In this work, we present a parametrical characterization of the features of the total electric field induced in material in response to an external incident field. We propose global parameters enabling characterization of the volume in which the squared modulus of the induced electric field is mainly concentrated, as well as the predominant state of polarization over the region where the power is significant. In addition, an uncertainty relationship is proven linking the region of concentration of the induced electric field and the region where its maximum rate of change occurs. [ABSTRACT FROM AUTHOR]

Background: The impact of lesion focality and centricity in relation to patient outcome and disease recurrence of vulvar intraepithelial neoplasia (VIN) is an understudied area of research, especially in immunocompromised women. The prevalence and incidence of VIN have increased steadily since the 1980s because of the co-existence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). In this study, we retrospectively examined the records of VIN patients to determine the effect of lesion focality and centricity with respect to the interval to disease recurrence.Materials and Methods: All women diagnosed with VIN and managed between January 2002 and December 2011 were included (n = 90) and followed up until December 2017. Symptoms at the time of presentation, including HIV positivity (n = 75), were collated, including the influences of multifocality and multicentricity on time to disease recurrence.Results: Multicentricity caused a more rapid recurrence of disease than unicentricity (p = 0.006), whereas multifocality increased the risk of recurrence more than unifocality (p < 0.0001). Viral load in the HIV+ patients was not associated with time to disease recurrence, but the reduced number of CD4+ lymphocytes present in HIV+ patients was. Treatment modalities had no effect on disease recurrence.Conclusion: Both focality and centricity have effects on interval to recurrence and final patient outcome, with multifocal disease having a poorer prognosis. Centricity and focality should be recorded at the time of diagnosis and act as a warning for disease recurrence. HIV+ VIN patients with multifocal disease and/or known immunosuppression (low CD4+ lymphocyte counts) should be regarded as "high-risk" patients and treated accordingly. [ABSTRACT FROM AUTHOR]

• Oral intake of cortisol does not affect focal and nonfocal prospective memory tasks. • This was observed independently of the influence of SNS and cognitive reappraisal. • Cortisol changes thus do not underlie potential stress effects on prospective memory. • Exploratory results suggest a circadian variation of prospective memory performance. Studies investigating effects of acute stress on Prospective Memory (PM) so far yielded heterogeneous findings. Although results were commonly attributed to stress-induced changes in cortisol, past research did not disentangle effects of cortisol from the effects of sympathetic nervous system (SNS) activation and cognitive reappraisal. The present study therefore aimed at investigating the mere effect of cortisol on PM tasks that differently involve prefrontal brain regions (nonfocal vs. focal PM tasks) via a placebo-controlled oral pharmacological intake of 10 mg hydrocortisone mimicking physiological responses to stress. Contrary to our prediction, enhanced levels of cortisol did not affect PM accuracy and monitoring costs, neither for the focal nor the nonfocal PM tasks. These results suggest that changes of cortisol levels do not underlie potential stress effects on PM. Further exploratory results revealed that PM performance was higher in the 3 pm than in the 1 pm placebo group. This means that PM performance, independently of effects of cortisol, seem to vary throughout the day. [ABSTRACT FROM AUTHOR]

We consider a methodology for studying how beliefs shape platform competition based on the notion of a partial focality. The concept of focality is useful for modeling platform competition when the presence of network effects results in multiple equilibria for a certain set of prices. We illustrate how to implement this methodology in both static and dynamic competition between platforms that differ in their basic quality. The initial degree of focality affects the ability of the high‐quality platform to win the market. Yet, dynamic considerations may have a positive or negative effect on this ability. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the prognostic value of the steroid hormone receptor expression, counting the retinoid X receptor (RXR) and thyroid hormone receptors (THRs), on the two different breast cancer (BC) entities: multifocal/multicentric versus unifocal. The overall and disease-free survival were considered as the prognosis determining aspects and analyzed by uni- and multi-variate analysis. Furthermore, histopathological grading and TNM staging (T = tumor size, N = lymph node involvement, M = distant metastasis) were examined in relation to RXR and THRs expression. A retrospective statistical analysis was carried out on survival-related events in a series of 319 sporadic BC patients treated at the Department of Gynecology and Obstetrics at the Ludwig-Maximillian’s University in Munich between 2000 and 2002. The expression of RXR and THRs, including its two major isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed to have a significant correlation for both BC entities in regard to survival analysis. Patients with multifocal/multicentric BC were exposed to a significantly worse disease-free survival (DFS) when expressing RXR. Patients with unifocal BC showed a significantly worse DFS when expressing THRα1. In contrast, a statistically significant positive association between THRα2 expression and enhanced DFS in multifocal/multicentric BC was shown. Especially the RXR expression in multifocal/multicentric BC was found to play a remarkably contradictory role for BC prognosis. The findings imply the need for a critical review of possible molecular therapies targeting steroid hormone receptors in BC treatment. Our results strengthen the need to further investigate the behavior of the nuclear receptor family, especially in relation to BC focality.

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm3 between the selected nine clinically relevant coil locations. Coil orientation also changed the induced E-field by a maximum of 10%, and we noted the least optimal values at the standard coil orientation pointing to the nose. The volume of gray matter activated varied by 10% on average between stimulation sites in homologous brain areas in the two hemispheres of the brain. This FEM simulation model clearly demonstrates the importance of TMS parameters for optimal results in clinically relevant brain areas. The results show that TMS parameters cannot be interchangeably used between individuals, hemispheres, and brain areas. The focality of the TMS induced E-field along with its optimal magnitude should be considered as critical TMS parameters that should be individually optimized.

The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) receptor expression might have on the two different breast cancer entities: multifocal/multicentric versus unifocal. As the prognosis determining aspects, we investigated the overall- and disease-free survival by uni-and multivariate analysis. To underline the study’s conclusion, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging system. A retrospective statistical analysis was performed on survival related events in a series of 289 sporadic breast cancer (BC) patients treated at the Department of Obstetrics and Gynecology at the Ludwig–Maximillian’s University in Munich between 2000 and 2002. The EP3 receptor expression was analyzed by immunohistochemistry and showed to have a significantly positive association with breast cancer prognosis for both entities, although with major differences. Patients with unifocal BC with EP3 receptor expression showed a significant improved overall survival, in contrast to the patient cohort with multifocal/multicentric BC. In this group, EP3 expression revealed its positive impact merely five years after initial diagnosis. Underlining the positive influence of EP3 as a positive prognosticator notably for unifocal breast cancer, only this patient cohort showed favorable outcomes in staging and grading. Especially EP3 expression in unifocal breast cancer was identified as an independent prognostic marker for the overall survival, when adjusted for age, grading, and staging. Altogether, our results strengthen the need to further investigate the behavior of EP3 in breast cancer and understand why markers linked to inflammation show different effects on prognosis and clinicopathological parameters on each focality type.

This paper conducts a comprehensive analysis on the impact of the coil size and the opening angle of twin coils on the stimulation depth and the focality. The finite-element method is utilized to analyze the head-model-inside distributions of the electric field induced by twin coils with various diameters and opening angles. The depth and focality of the electric field are quantified based on the simulation results. It shows that the depth can reach to optimal value by adjusting opening angle. Meanwhile, increasing twin coil size can improve both the depth and the focality. In addition, the experimental results are also given to further validate the conclusion drawn from the computational simulation results. The presented results show significant meanings for researchers and clinicians to design or configure the optimal twin coil for the transcranial magnetic stimulation systems. [ABSTRACT FROM AUTHOR]

Objective To investigate inter-subject variability with respect to cerebrospinal fluid thickness and brain-scalp distance, and to investigate intra-subject variability with different coil orientations. Methods Simulations of the induced electric field (E-Field) using a figure-8 coil over the vertex were conducted on 50 unique head models and varying orientations on 25 models. Metrics exploring stimulation intensity, spread, and localization were used to describe inter-subject variability and effects of non-brain anatomy. Results Both brain-scalp distance and CSF thickness were correlated with weaker stimulation intensity and greater spread. Coil rotations show that for the dorsal portion of the stimulated brain, E-Field intensities are highest when the anterior-posterior axis of the coil is perpendicular to the longitudinal fissure, but highest for the medial portion of the stimulated brain when the coil is oriented parallel to the longitudinal fissure. Conclusions Normal anatomical variation in healthy individuals leads to significant differences in the site of TMS, the intensity, and the spread. These variables are generally neglected but could explain significant variability in basic and clinical studies. Significance This is the first work to show how brain-scalp distance and cerebrospinal fluid thickness influence focality, and to show the disassociation between dorsal and medial TMS. [ABSTRACT FROM AUTHOR]

Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slower responding) to ongoing activities. However, research suggests that individuals are able to monitor strategically by using contextual cues to reduce monitoring in contexts in which PM targets are not expected to occur. In the current study, we investigated the processes supporting context identification (i.e., determining whether or not the context is appropriate for monitoring) by testing the context cue focality hypothesis. This hypothesis predicts that the ability to monitor strategically depends on whether the ongoing task orients attention to the contextual cues that are available to guide monitoring. In Experiment 1, participants performed an ongoing lexical decision task and were told that PM targets (TOR syllable) would only occur in word trials (focal context cue condition) or in items starting with consonants (nonfocal context cue condition). In Experiment 2, participants performed an ongoing first letter judgment (consonant/vowel) task and were told that PM targets would only occur in items starting with consonants (focal context cue condition) or in word trials (nonfocal context cue condition). Consistent with the context cue focality hypothesis, strategic monitoring was only observed during focal context cue conditions in which the type of ongoing task processing automatically oriented attention to the relevant features of the contextual cue. These findings suggest that strategic monitoring is dependent on limited-capacity processing resources and may be relatively limited when the attentional demands of context identification are sufficiently high. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non-invasive neuro-stimulation based on the principle of electromagnetic induction that uses brief, strong magnetic pulses of electric current delivered to a coil placed on the subject’s head to induce an electric field in the brain. This electric field could stimulate and modulate neural activity. Induced E-field inside brain generated by repetitive TMS (rTMS) can produce changes in neural activity that extends beyond the period of stimulation. Therefore, rTMS can be used as a probe for exploring higher brain functions and as potential treatment technique for psychiatric and neurological disorders. However, based on the chosen shape of the excitation coil, there exists a tradeoff between the excitation focality in the brain and the depth to which the field penetrates. In this paper, a new design of TMS coil is proposed to enhance the performance of the traditional figure-of-eight (FOE) coil. 3-D finite-element method has been used to simulate and compare the electric field induced inside the model of a human brain under the influence of both coil designs. An experimental verification was then followed to validate the advantages of the proposed coil design over the classic FOE coil. [ABSTRACT FROM AUTHOR]

Large-scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual-site Transcranial Alternating Current Stimulation (ds-TACS) has been recently introduced as non-invasive technique to manipulate the temporal phase relationship of local oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation parameters such as focality and stimulation intensity should be matched to enable an unambiguous interpretation of the behavioral effects. Using electric field simulations based on a realistic head geometry, we tested how well this goal has been met in studies, which have employed ds-TACS up to now. Separating the induced electrical fields in their spatial and temporal components, we investigated how the chosen electrode montages determined the spatial field distribution and the generation of phase variations in the injected electric fields. Considering the basic physical mechanisms, we derived recommendations for an optimized stimulation montage. The latter allows for a principled design of in- and anti-phase ds-TACS conditions with matched spatial distributions of the electric field. This knowledge will help cognitive neuroscientists to design optimal ds-TACS configurations, which are suited to probe unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain. [ABSTRACT FROM AUTHOR]

The retention phase of a prospective memory (PM) task poses different challenges, including demands to store or maintain an intended action and to realize the right moment for action execution. The interplay of these processes in younger and older adults has not been explored so far. In this study, the authors examined the impact of maintenance load and task focality on PM in 84 younger and in 83 older adults. Results indicated that PM performance and ongoing task response times were strongly affected by maintenance load and age. However, a focality effect only emerged when maintenance load was low but not when attentional resources were deployed for maintaining a more demanding intention. These findings suggest that maintenance and monitoring requirements compete for similar attentional resources. Furthermore, maintenance load may affect postretrieval processes through its impact on working-memory resources, which can restrain the typical advantage of focal over nonfocal PM tasks. [ABSTRACT FROM AUTHOR]

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This paper presents a novel noninvasive electromagnetic brain stimulation system, namely the transcranial magnetic stimulation (TMS), via strongly coupled magnetic resonances, which is used to improve treatment effects, enrich treatment means, and increase energy utilizations. To achieve expected stimulation effects, the conventional TMS system normally needs strict requirements for the power supply and the circuit. Inevitably, it not only deteriorates the implementability and flexibility of the noninvasive electromagnetic brain stimulation, but also increases the manufacture cost and energy consumption, thus significantly impeding the popularization of TMS technologies. Hence, a novel TMS system is proposed by utilizing the magnetic resonant coupling (MRC) mechanism, aiming to offer a brand new way to fulfill expected stimulation effects. By comparing with conventional TMS systems, the proposed system can effectively increase the strength so as to improve the stimulation depth, enhance the focality so as to prevent from impacting on nonfocal zones, and reduce the requirement on the power and frequency so as to promote the popularization of noninvasive electromagnetic treatments. In this paper, both simulation and experimental results are provided to verify the feasibility and superiority of the proposed MRC-based TMS system. [ABSTRACT FROM AUTHOR]

Large river valleys have long been seen as important factors to shape the mobility, communication, and exchange of Pleistocene hunter-gatherers. However, rivers have been debated as either natural entities people adapt and react to or as cultural and meaningful entities people experience and interpret in different ways. Here, we attempt to integrate both perspectives. Building on theoretical work from various disciplines, we discuss the relationship between biophysical river properties and sociocultural river semantics and suggest that understanding a river's persona is central to evaluating its role in spatial organization. By reviewing the literature and analyzing European Upper Paleolithic site distribution and raw material transfer patterns in relation to river catchments, we show that the role of prominent rivers varies considerably over time. Both ecological and cultural factors are crucial to explaining these patterns. Whereas the Earlier Upper Paleolithic record displays a general tendency toward conceiving rivers as mobility guidelines, the spatial consolidation process after the colonization of the European mainland is paralleled by a trend of conceptualizing river regimes as frontiers, separating archaeological entities, regional groups, or local networks. The Late Upper Paleolithic Magdalenian, however, is characterized again by a role of rivers as mobility and communication vectors. Tracing changing patterns in the role of certain river regimes through time thus contributes to our growing knowledge of human spatial behavior and helps to improve our understanding of dynamic and mutually informed human-environment interactions in the Paleolithic. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that neural plasticity impairments, observed in schizophrenia patients, are driven by dysfunctional integration of neural signaling. However, what is less clear is whether this impairment is resultant from a general deficit in plastic induction or whether a specific plastic mechanism is affected. In the current study we aimed to assess whether schizophrenia has a selective impact on focal or non-focal plasticity induction. To pursue this goal we utilized two non-invasive stimulation techniques that differ in the mechanism of long-term potentiation (LTP)-like plasticity induction: focal paired associative stimulation (PAS) and non-focal anodal transcranial direct current stimulation (a-tDCS). 20 schizophrenia patients and 20 matched healthy controls received PAS and a-tDCS in two separate sessions. Cortical excitability and cortical plasticity were assessed by transcranial magnetic stimulation (TMS)-elicited motor evoked potentials (MEP). In both study groups, non-focal a-tDCS resulted in a significant increase of mean MEP magnitude indicating the successful induction of non-focal LTP-like plasticity. In contrast, an increase in mean MEP magnitude following PAS was only observed in the control group, suggesting impaired focal LTP-like plasticity in schizophrenia. Additionally, we observed significantly impaired short-latency intracortical inhibition (SICI) in schizophrenia. This is the first study to comparatively evaluate non-focal and focal plasticity mechanisms in schizophrenia patients. The differential patterns of LTP-like plasticity responses indicate that reduced plasticity in schizophrenia could be ascribed to impairments in spatially and temporally restricted signal integration. This impairment, coupled with an observed reduction of inhibitory circuit efficacy, might further contribute to impairments in coordinating focal signals. [ABSTRACT FROM AUTHOR]

Objective We propose the use of a new montage for transcranial direct current stimulation (tDCS), called concentric electrodes tDCS (CE-tDCS), involving two concentric round electrodes that may improve stimulation focality. Methods To test efficacy and focality of CE-tDCS, we modelled the current distribution and tested physiological effects on cortical excitability. Motor evoked potentials (MEPs) from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) were recorded before and after the delivery of anodal, cathodal and sham stimulation on the FDI hotspot for 10 minutes. Results MEP amplitude of FDI increased after anodal-tDCS and decreased after cathodal-tDCS, supporting the efficacy of CE-tDCS in modulating cortical excitability. Moreover, modelled current distribution and no significant effects of stimulation on MEP amplitude of ADM suggest high focality of CE-tDCS. Conclusions CE-tDCS may allow a better control of current distribution and may represent a novel tool for applying tDCS and other transcranial current stimulation approaches. [ABSTRACT FROM AUTHOR]

Background In transcranial magnetic stimulation (TMS) a strong, brief current pulse driven through a coil is used for non-invasively stimulating the cortex. Properties of the electric field (E-field) induced by the pulse together with physiological parameters determine the outcome of the stimulation. In research and clinical use, TMS is delivered using a wide range of different coils and stimulator units, all having their own characteristics; however, the parameters of the induced E-field are often inadequately known by the user. Objective To better understand how the use of a specific TMS device may affect the resulting cortical stimulation, our objective was to develop an instrument for automated measurement of the E-fields induced by TMS coils in spherically symmetric conductors approximating the head. Methods We built a saline-free, robotized measurement tool based on the triangle construction. The 5-mm-wide measurement probe allows complete sampling of the induced E-field at the studied depth. We used the instrument to characterize TMS coils and stimulators made by two companies. Results The measurements revealed that all tested stimulators performed as expected, but we also found significant differences between the different stimulators. Measurements of different coil specimens of the same stimulator models agreed with each other. Conclusion The presented TMS calibrator allows a straightforward characterization of the E-fields induced by TMS coils. By performing measurements using this kind of a tool helps in ensuring that an investigator knows the properties of the E-field. [ABSTRACT FROM AUTHOR]

Background In transcranial magnetic stimulation (TMS), the stimulation-coil current is typically increased from 0 to over 5000 A in less than 100 μ s. At the peak current, the energy stored in the magnetic field is over 300 J. Thus, the average power during a pulse exceeds 3 MW; the stimulator needs to be built from high-power electronics. The power requirements often limit the duration and frequency of repetitive TMS, for example, via coil heating. Objective We introduce a method for finding the minimum-energy solution for a TMS coil with given focality constraints. Methods This optimization is performed by using a spherically symmetric head model and by expressing the coil as a continuous surface current density, which is eventually discretized to form the coil windings. For the optimization, we defined TMS focality separately for the directions parallel and perpendicular to the field direction at the maximum of induced electric field. Results The computational model used for optimization was verified by manufacturing a prototype coil and measuring the electric field it induces in a spherically symmetric conductor. The optimized coil design requires significantly less power than existing TMS coil designs (a 73% reduction compared to an existing TMS coil with similar focality). Conclusion The described method allows for more efficient, more focal TMS coils, which may reduce coil heating and the coil click. [ABSTRACT FROM AUTHOR]