Computational analysis of electrode structure and configuration for efficient and localized neural stimulation.

Neuromodulation technique using electric stimulation is widely applied in neural prosthesis, therapy, and neuroscience research. Various stimulation techniques have been developed to enhance stimulation efficiency and to precisely target the specific area of the brain which involves optimizing the geometry and the configuration of the electrode, stimulation pulse type and shapes, and electrode materials. Although the effects of electrode shape, size, and configuration on the performance of neural stimulation have individually been characterized, to date, there is no integrative investigation of how this factor affects neural stimulation. In this study, we computationally modeled the various types of electrodes with varying shapes, sizes, and configurations and simulated the electric field to calculate the activation function. The electrode geometry is then integratively assessed in terms of stimulation efficiency and stimulation focality. We found that stimulation efficiency is enhanced by making the electrode sharper and smaller. A center-to-vertex distance exceeding 100 µm shows enhanced stimulation efficiency in the bipolar configuration. Additionally, the separation distance of less than 1 mm between the reference and stimulation electrodes exhibits higher stimulation efficiency compared to the monopolar configuration. The region of neurons to be stimulated can also be modified. We found that sharper electrodes can locally activate the neuron. In most cases, except for the rectangular electrode shape with a center-to-vertex distance smaller than 100 µm, the bipolar electrode configuration can locally stimulate neurons as opposed to the monopolar configuration. These findings shed light on the optimal selection of neural electrodes depending on the target applications.

Self-reported strategy use and prospective memory: The roles of cue focality and task importance.

Interest in the metacognitive aspects of prospective memory (PM) is growing. Yet, the interplay between participants' metacognitive awareness of PM task demands and features that contribute to successful PM require further attention. To this aim, participants in the current study completed laboratory-based PM tasks of varying difficulty (cue focality: focal, nonfocal-category, or nonfocal-syllable) and reported their strategy use and perceptions of PM task importance. Most participants reported using a strategy regardless of cue focality. However, only under the most challenging condition (i.e., nonfocal-syllable) did participants who reported using a strategy exhibit better PM performance compared to those who did not use a strategy. Additionally, strategy use and cue focality were independently associated with greater costs to ongoing task performance: strategy users exhibited greater slowing relative to individuals who did not use a strategy, and the extent of slowing was greater as the task difficulty increased across cue focality. Finally, perceived task importance appeared to play an important role in the interactive link between cue focality and strategy use on PM performance for the more challenging, nonfocal PM tasks. Specifically, moderation analyses suggested that greater perceived task importance alone may improve the likelihood of PM success for moderately challenging PM tasks (i.e., nonfocal-category), but for the most challenging PM tasks (i.e., nonfocal-syllable), individuals' strategy use was still associated with better PM performance. The present study expands our understanding of metacognition's role in PM performance and has implications for everyday PM performance.

Effect of negative emotion on prospective memory and its different components.

Prospective memory is an important and complex social cognitive ability, which is easily disturbed by negative emotions. According to the relationship between prospective memory cues and ongoing tasks, prospective memory can be divided into focal prospective memory and non-focal prospective memory. This study focuses on the influence of negative emotions on different types of prospective memory. In Experiment 1, 117 participants were recruited, using a 2 (emotion: negative, neutral) × 2 (cue focality: focal, non-focal) between-subjects design to initially explore whether negative emotions can interfere with the prospective memory of both focal cue and non-focal cue. The results show that negative emotions simultaneously reduce both types of prospective memory performance. At the same time, negative emotions occupy additional attention resources and impair the prospective component of prospective memory with non-focal cues. In Experiment 2, 64 participants were recruited to improve the difficulty of the retrospective component of prospective memory with non-focal cues, and the influence of negative emotions on different components of prospective memory with non-focal cues was further explored. The results show that negative emotions can impair both the prospective and retrospective components of prospective memory. In short, the results of this study indicate that negative emotion can impair prospective memory, and the impairment effect is not limited by the cue type of prospective memory. Meanwhile, negative emotion will occupy more attentional resources and simultaneously affect the prospective and retrospective components of prospective memory.

How do the cognitive processes matter in the event-based preschoolers' prospective memory?

Background: Prospective memory (PM) is the ability to remember to perform an intended action at a specific future moment. The current study examined the impact of age, task focality, and cue salience on PM in children aged 2 to 6 years, based on the multiprocess theory of PM and the executive framework of PM development. Additionally, the study explored the relationship between various cognitive abilities and their association with PM performance. Methods: A total of 224 preschool-aged children, aged 2-6, engaged in event-based PM tasks with varying cognitive demands. The tasks were either focal or nonfocal, with salient or nonsalient cues. Additionally, individual differences in cognitive abilities were measured. Results: The results support previous indications that even very young children can successfully complete event-based PM tasks. The accuracy of PM display improved with age, especially between the ages of 3 and 4. Better performance was observed in focal PM tasks compared to nonfocal PM tasks. Additionally, preschoolers' PM performance correlated with various cognitive abilities, including fluid intelligence, retrospective memory, inhibitory control, working memory, and language ability. These correlations varied depending on the child's age and the task's nature. For both focal and nonfocal PM tasks, cognitive abilities partially mediated the relationship between age and PM performance. Conclusion: In summary, this study comprehensively explores the specific roles played by age and fundamental cognitive abilities in event-based PM performance among preschool-aged children.

Immunohistochemical markers as predictors of prognosis in multifocal prostate cancer.

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.

Integrating electric field modeling and pre-tDCS behavioral performance to predict the individual tDCS effect on visual crowding.

Objective.Transcranial direct current stimulation (tDCS) has been broadly used to modulate brain activity with both bipolar and high-definition montages. However, tDCS effects can be highly variable. In this work, we investigated whether the variability in the tDCS effects could be predicted by integrating individualized electric field modeling and individual pre-tDCS behavioral performance.Approach.Here, we first compared the effects of bipolar tDCS and 4 × 1 high-definition tDCS (HD-tDCS) with respect to the alleviation of visual crowding, which is the inability to identify targets in the presence of nearby flankers and considered to be an essential bottleneck of object recognition and visual awareness. We instructed subjects to perform an orientation discrimination task with both isolated and crowded targets in the periphery and measured their orientation discrimination thresholds before and after receiving 20 min of bipolar tDCS, 4 × 1 HD-tDCS, or sham stimulation over the visual cortex. Individual anatomically realistic head models were constructed to simulate tDCS-induced electric field distributions and quantify tDCS focality. Finally, a multiple linear regression model that used pre-tDCS behavioral performance and tDCS focality as factors was used to predict post-tDCS behavioral performance.Main results.We found that HD-tDCS, but not bipolar tDCS, could significantly alleviate visual crowding. Moreover, the variability in the tDCS effect could be reliably predicted by subjects' pre-tDCS behavioral performance and tDCS focality. This prediction model also performed well when generalized to other two tDCS protocols with a different electrode size or a different stimulation intensity.Significance.Our study links the variability in the tDCS-induced electric field and the pre-tDCS behavioral performance in a visual crowding task to the variability in post-tDCS performance. It provides a new approach to predicting individual tDCS effects and highlights the importance of understanding the factors that determine tDCS effectiveness while developing more robust protocols.

Interindividual differences in posterior fossa morphometry affect cerebellar tDCS-induced electric field strength.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SIGNIFICANCE: 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.

Prospective memory: the combined impact of cognitive load and task focality.

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.

Does total tumour diameter, multifocality, number of tumour foci, or laterality predict lymph node metastasis or recurrence in differentiated thyroid cancer?

INTRODUCTION: Data regarding laterality, focality, or total tumour diameter (TTD) in papillary thyroid cancer (PTC) are limited. We aimed to investigate the impact of focality, TTD, number of tumour foci, or laterality on aggressive features in PTC. MATERIAL AND METHODS: Patients were categorized based on maximum tumour diameter (MTD) (≤ 10 vs. > 10 mm), focality, laterality, or the number of tumour foci (1/2/ ≥ 3). We also categorized the patients as follows: Group 1, unifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 2, multifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 3, multifocal microcarcinoma (MTD ≤ 10/TTD > 10 mm); Group 4, unifocal macrocarcinoma (MTD > 10/TTD > 10 mm); Group 5, multifocal macrocarcinoma (MTD > 10/TTD > 10 mm). RESULTS: The mean diagnosis age (n = 511) was 44.7 (± 12.7) years, the majority of the patients were < 55 years old (n = 310) and female (n = 416). An increasing number of tumour foci were associated with a higher MTD or TTD, a higher ratio of extrathyroidal extension (ETE), vascular or lymphatic invasion, lymph node metastasis (LNM) or distant metastasis, or the need for radioactive iodine (RAI). There was no difference in the parameters between Group 3 and Group 2, or Group 4. Vascular invasion, American Thyroid Association high risk, LNM at diagnosis, and RAI total dose were higher in Group 5 than in Group 3. Microscopic or macroscopic ETE, T1b, and T4a were positive predictors for recurrence. Male sex, multifocality, number of tumour foci (≥ 3), MTD (> 10 mm), TTD (> 10 mm), Group 5, microscopic or macroscopic ETE, lymphatic or vascular invasion, RAI need, T2, and T4b were positive predictors for LNM. CONCLUSION: MTD and TTD increase the risk of LNM but not the recurrence in PTC. TTD, multifocality, and bilaterality can be considered risk factors in PTC staging systems and risk calculators.

A thorough examination of cue specificity and task-appropriateness in defining focal and nonfocal prospective memory tasks.

Prospective memory (PM) - memory for future intentions - has a core term called focality which describes how closely a PM task relates to an ongoing task. When a close relationship exists between an ongoing and PM task, the task is classified as focal (loose relationships are classified as nonfocal). Competing PM theories differ primarily in explanations for how focality changes participants' approaches. Researchers classify PM intentions as focal or nonfocal in two ways: (1) task appropriateness, congruency (TAP) or incongruency (TIP) of processing to complete both tasks, and (2) cue specificity, specific or general task cues. Independently manipulating this ambiguity in defining "focality" was our current focus. Participants were randomly assigned to a control group, a focal PM condition, or one of three nonfocal conditions. Their ongoing task involved a semantic judgment (Experiment 1) or an orthographic judgment (Experiment 2). Cue specificity impacted PM accuracy consistently, favouring specific cues. Task-appropriateness impacted PM accuracy in Experiment 1, but not in Experiment 2 which showed protective effects for specific, whole-word PM cues - emphasizing the role that deeper processing has on PM success. These studies highlight the ambiguity in the operational definition of focality and provide the groundwork for continued refinement of the definition.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Focality and prospective memory in preschool children.

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.

Drug resistance in idiopathic generalized epilepsies: Evidence and concepts.

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.

Variation of cerebrospinal fluid in specific regions regulates focality in transcranial direct current stimulation.

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).

ERP Correlates of Prospective Memory and Cue Focality in Children.

Prospective memory (PM) is essential in the everyday activities of children because it involves remembering intentions for the future, such as doing their homework or bringing written parental permissions to school. Developmental studies have shown increases in PM performance throughout childhood, but the specific processes underlying this development are still under debate. In the present study, event-related potentials were used to examine whether the focality of the PM task is related to the PM increments by testing two groups of children (first and last cycle of primary school) and assessing differences in N300 (cue detection), frontal positivity (switching), parietal positivity (retrieval of the intention) and frontal slow waves (monitoring of the retrieved intention). The results showed significant differences in focality in the group of older children but no differences in any of the components for their younger counterparts. In addition, the differences between prospective and ongoing trials were smaller for younger than older children. These findings suggest that the ability to adjust attentional strategies, monitor, switch and retrieve the intention develops across childhood and affects PM performance in attentionally demanding conditions.

Prospective memory in bilinguals and monolinguals: ERP and behavioural correlates of prospective processing in bilinguals.

Prospective memory (PM) allows us to form intentions and execute them in the future. Successful retrieval of prospective intentions depends on adequate context monitoring and disengagement from the ongoing task. These processes are also central in predicting incoming language information and guiding language production in bilinguals. We investigated if different bilingual experiences (early/late bilinguals, monolinguals) modulate performance in PM tasks that varied in attentional requirements (focal vs. non-focal). Behavioural and event-related potential (ERP) results indicated that early bilinguals differed from late bilinguals and monolinguals in how they performed the prospective task. Specifically, they showed larger differences between the ongoing activity and the prospective task in the N300 and P3b components when performing the more difficult non-focal PM task, indicating that they engaged in monitoring/updating to adapt to the task's demands. These differences were not observed in late bilinguals and monolinguals, suggesting that prospective processing is dependent on the bilingual experience.

Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma.

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.

Magnetically Induced Temporal Interference for Focal and Deep-Brain Stimulation.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that has been clinically applied for neural modulation. Conventional TMS systems are restricted by the trade-off between depth penetration and the focality of the induced electric field. In this study, we integrated the concept of temporal interference (TI) stimulation, which has been demonstrated as a non-invasive deep-brain stimulation method, with magnetic stimulation in a four-coil configuration. The attenuation depth and spread of the electric field were obtained by performing numerical simulation. Consequently, the proposed temporally interfered magnetic stimulation scheme was demonstrated to be capable of stimulating deeper regions of the brain model while maintaining a relatively narrow spread of the electric field, in comparison to conventional TMS systems. These results demonstrate that TI magnetic stimulation could be a potential candidate to recruit brain regions underneath the cortex. Additionally, by controlling the geometry of the coil array, an analogous relationship between the field depth and focality was observed, in the case of the newly proposed method. The major limitations of the methods, however, would be the considerable intensity and frequency of the input current, followed by the frustration in the thermal management of the hardware.

Trade-off between stimulation focality and the number of coils in multi-locus transcranial magnetic stimulation.

Objective. Coils designed for transcranial magnetic stimulation (TMS) must incorporate trade-offs between the required electrical power or energy, focality and depth penetration of the induced electric field (E-field), coil size, and mechanical properties of the coil, as all of them cannot be optimally met at the same time. In multi-locus TMS (mTMS), a transducer consisting of several coils allows electronically targeted stimulation of the cortex without physically moving a coil. In this study, we aimed to investigate the relationship between the number of coils in an mTMS transducer, the focality of the induced E-field, and the extent of the cortical region within which the location and orientation of the maximum of the induced E-field can be controlled.Approach.We applied convex optimization to design planar and spherically curved mTMS transducers of different E-field focalities and analyzed their properties. We characterized the trade-off between the focality of the induced E-field and the extent of the cortical region that can be stimulated with an mTMS transducer with a given number of coils.Main results.At the expense of the E-field focality, one can, with the same number of coils, design an mTMS transducer that can control the location and orientation of the peak of the induced E-field within a wider cortical region.Significance. With E-fields of moderate focality, the problem of electronically targeted TMS becomes considerably easier compared with highly focal E-fields; this may speed up the development of mTMS and the emergence of new clinical and research applications.

Relationships Between Indices of Tumor Aggressiveness in Hepatocellular Carcinoma.

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.