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Background: Current atherosclerotic cardiovascular disease (ASCVD) risk assessment tools like the Pooled Cohort Equations (PCEs) and PREVENT™ scores offer long-term predictions but may not effectively drive behavior change. Short-term risk predictions using mobile health (mHealth) data and electronic health records (EHRs) could enhance clinical decision-making and patient engagement. The aim of this study was to develop a short-term ASCVD risk prediction model for hypertensive individuals using mHealth and EHR data and compare its performance to existing risk assessment tools., Methods: This is a retrospective cohort study including 51,127 hypertensive participants aged ≥18 years old who enrolled in the Hello Heart CV risk self-management program between January 2015 and January 2024. A machine learning (ML) model was derived from EHR data and mHealth measurements of blood pressure (BP) and heart rate (HR) collected via at-home BP monitors. Its performance was compared to that of PCE and PREVENT., Results: The XgBoost model incorporating 291 features outperformed the PCE and PREVENT scores in discriminating ASCVD risk for both prediction periods. For 90-day prediction, mean C-statistics were 0.81 (XgBoost) vs. 0.74 (PCE) and 0.65 (PREVENT). Similar findings were observed for 365-day prediction. mHealth measurements incrementally enhanced 365-day risk prediction (ROC-AUC 0.82 vs. 0.80 without mHealth)., Conclusion: An EHR and mHealth-based ML model offers superior short-term ASCVD prediction compared to traditional tools. This approach supports personalized preventive strategies, particularly for populations with incomplete features for PCE or PREVENT. Further research should explore this novel risk prediction framework, and particularly additional mHealth data integration for broader applicability and increased predictive power., Competing Interests: TG, HL, EP, HM, SG, PA, GP, LV, and AD are employed by Hello Heart and receive equity from Hello Heart. EP is also employed by White Plains Hospital. EZ is employed by Sheba Medical Center, Tel Hashomer and is an advisor for Hello Heart and receives consulting fees. JP is employed by Scripps Research Translational Institute and the Scripps Research team was funded by the National Center for Advancing Translational Sciences at the National Institutes of Health (UM1TR004407)., (© 2024 Gazit, Mann, Gaber, Adamenko, Pariente, Volsky, Dolev, Lyson, Zimlichman, Pandit and Paz.)

Background: Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors., Methods and Results: Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m 2 . At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m 2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes., Conclusions: A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.

The use of bioabsorbable magnesium (Mg) screws is new in foot surgery. Their relative merit over conventional titanium screws has not yet been proven. This prospective case series study was conducted to compare the clinical and radiological outcomes of bioabsorbable Mg screws and titanium screws. A consecutive series of patients (n = 60; 11 men and 49 women) underwent corrective hallux valgus surgery. The minimum follow-up period was 1 year. The assessment was based on a patient questionnaire, including the American Orthopedic Foot and Ankle Society (AOFAS) hallux valgus score, visual analog scale, patient's global impression of change (PGIC), and fifth metatarsus circumference (IF5C). The radiographic assessment included the intermetatarsal and hallux valgus angles, as well as time to osteotomy union and hardware failure. At 1 year, similar results were obtained radiographically. The healing of the osteotomies was significantly faster in the Mg group. Hardware failure was common in the Mg group (5/26) than in the TI group (0/34) but hardware removal was more common in the TI group (6/34) versus the MG group (0/26). IF5C increased by 8 ± 2 mm in the Mg group. The AOFAS and PGIC scores at 6 months were similar. Validated foot scores and radiographic analysis indicated that there was no detectable difference between the groups. The fast achievement of osteotomy union compensates for a high rate of hardware failure, resulting in patient satisfaction and avoiding reoperation for hardware removal., (Copyright © 2023 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Linking scalp electroencephalography (EEG) signals and spontaneous firing activity from deep nuclei in humans is not trivial. To examine this, we analyzed simultaneous recordings of scalp EEG and unit activity in deeply located sites recorded overnight from patients undergoing pre-surgical invasive monitoring. We focused on modeling the within-subject average unit activity of two medial temporal lobe areas: amygdala and hippocampus. Linear regression model correlates the units' average firing activity to spectral features extracted from the EEG during wakefulness or non-REM sleep. We show that changes in mean firing activity in both areas and states can be estimated from EEG (Pearson r > 0.2, p≪0.001). Region specificity was shown with respect to other areas. Both short- and long-term fluctuations in firing rates contributed to the model accuracy. This demonstrates that scalp EEG frequency modulations can predict changes in neuronal firing rates, opening a new horizon for non-invasive neurological and psychiatric interventions., Competing Interests: T.H. is an employee and shareholder of GrayMatters Health Ltd., (© 2023 The Authors.)

Background: Several approaches are used to access the hip joint; most common are the direct lateral and posterior. Little consensus exists on which to use when treating hip fractures., Objectives: To compare short-term complications, postoperative ambulation, and patient-reported outcome measures (PROMS) of direct lateral vs. posterior approaches in hemiarthroplasty for acute hip fractures., Methods: We conducted a retrospective clinical trial with 260 patients who underwent bipolar hemiarthroplasty in the direct lateral or posterior approach (166 and 94, respectively) between January 2017 and December 2018. The clinical data included short-term complications: prosthetic dislocation, periprosthetic fractures, and infection. Postoperative ambulation was collected 6 weeks postoperatively; PROMS were collected for 173 patients at 2 years follow-up., Results: There were six dislocations overall, average time to dislocation was 22 days postoperative (range 4-34). Five dislocations were after the posterior approach (5.3%) and one after direct lateral (0.6%) (P = 0.01). At 6 weeks follow-up, inability to walk was found in 16.9% of the direct lateral group and 6.4% of the posterior approach group (P = 0.02). In the posterior approach group, 76% could walk more than 20 meters; only half of the direct lateral group could (P = 0.0002). At 2 years follow-up, PROMS did not show a statistically significant difference between the groups., Conclusions: Posterior approach for hemiarthroplasty following femoral neck fractures allows superior ambulation to the direct lateral approach only for the short-term. However, no long-term clinical advantage was found. This short-term benefit does not justify the increased dislocation rate in the posterior approach.

Importance: It is unclear whether mobile technology hypertension self-management programs are associated with blood pressure (BP) control., Objective: To examine whether engagement with a hypertension self-management program with a BP monitor and connected smartphone application with clinically based digital coaching was associated with BP control during a follow-up period of as long as 3 years., Design, Setting, and Participants: This cohort study enrolled US adults with elevated BP or hypertension between January 1, 2015, and July 1, 2020. The hypertension self-management program was provided through the participant's (or their spouse's) employer health plan., Exposures: Program engagement, defined by average number of application sessions., Main Outcomes and Measures: Systolic and diastolic BP measured by a US Food and Drug Administration-cleared BP monitor, with categories defined as normal (systolic BP, <120 mm Hg), elevated (systolic BP, 120-129 mm Hg), stage 1 hypertension (systolic BP, 130-139 mm Hg), and stage 2 hypertension (systolic BP ≥140 mm Hg). Other measures included age, gender, depression, anxiety, diabetes, high cholesterol, smoking, geographic region, area deprivation index, self-reported weight, and device-measured physical activity (steps per day)., Results: Among 28 189 participants (median [IQR] age, 51 [43-58] years; 9424 women [40.4%]; 13 902 men [59.6%]), median (IQR) baseline systolic BP was 129.5 mm Hg (120.5-139.6 mm Hg) and diastolic BP was 81.7 mm Hg (75.7-88.4 mm Hg). Median systolic BP at 1 year improved at least 1 category for 495 of 934 participants (53.0%) with baseline elevated BP, 673 of 966 (69.7%) with baseline stage 1 hypertension, and 920 of 1075 (85.7%) with baseline stage 2 hypertension. Participants in the program for 3 years had a mean (SEM) systolic BP reduction of 7.2 (0.4), 12.2 (0.7), and 20.9 (1.7) mm Hg compared with baseline for those starting with elevated, stage 1 hypertension, and stage 2 hypertension, respectively. Greater engagement was associated with lower systolic BP over time (high-engagement group: 131.2 mm Hg; 95% CI, 115.5-155.8 mm Hg; medium-engagement group: 133.4 mm Hg; 95% CI 116.3-159.5 mm Hg; low-engagement group: 135.5 mm Hg; 95% CI, 117.3-164.8 mm Hg; P < .001); these results persisted after adjusting for age, gender, depression, anxiety, diabetes, high cholesterol, smoking, area deprivation index rank, and US region, which was partially mediated by greater physical activity. A very high BP (systolic BP >180 mm Hg) was observed 11 637 times from 3778 participants. Greater engagement was associated with lower risk of very high BP; the estimated probability of a very high BP was greater in the low-engagement group (1.42%; 95% CI, 1.26%-1.59%) compared with the medium-engagement group (0.79%; 95% CI, 0.71%-0.87%; P < .001) and the high-engagement group (0.53%; 95% CI, 0.45%-0.60%; P < .001 for comparison with both groups)., Conclusions and Relevance: The findings of this study suggest that a mobile technology hypertension self-management program can support long-term BP control and very high BP detection. Such programs may improve real-world BP monitoring and control.

Objectives: Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC., Methods: We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways., Results: 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus., Significance: Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Polymicrogyria (PMG) is a common malformation of cortical development associated with a higher susceptibility to epileptic seizures. Seizures secondary to PMG are characterized by difficult-to-localize cerebral sources due to the complex and widespread lesion structure. Tracing the dynamics of interictal epileptiform discharges (IEDs) in patients with epilepsy has been shown to reveal the location of epileptic activity sources, crucial for successful treatment in cases of focal drug-resistant epilepsy. In this case series IED dynamics were evaluated with simultaneous EEG-fMRI recordings in four patients with unilateral peri-sylvian polymicrogyria (PSPMG) by tracking BOLD activations over time: before, during and following IED appearance on scalp EEG. In all cases, focal BOLD activations within the lesion itself preceded the activity associated with the time of IED appearance on EEG, which showed stronger and more widespread activations. We therefore propose that early hemodynamic activity corresponding to IEDs may hold important localizing information potentially leading to the cerebral sources of epileptic activity. IEDs are suggested to develop within a small area in the PSPMG lesion with structural properties obscuring the appearance of their electric field on the scalp and only later engage widespread structures which allow the production of large currents which are recognized as IEDs on EEG., Competing Interests: FF, TH, and MM are authors of patent: Device for use in electro-biological signal measurement in the presence of a magnetic field, WO2012046237, 12.04.2012. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cohen, Ebrahimi, Medvedovsky, Gurevitch, Aizenstein, Hendler, Fahoum and Gazit.)

Women dealing with infertility issues may well undergo a long process of treatments and they are also likely to feel empty, defective, inadequate and worthless. Some of these women join online support groups in order to share their experiences, get information and ease their pain. One important positive phenomenon of the Internet is the advent of online support groups. These are designed to foster well-being and increased social interaction, and to offer 24/7 availability with no geographical restrictions. This study, comprising 191 female participants who answered an online survey, focused on closed Facebook support groups, the members of which were women undergoing treatments for infertility. The study examined to what extent the degree of engagement by these women in online support groups could be predicted by external factors (family status, social and family support, the importance of the group and the duration of membership) and internal factors (extroversion, openness to experience, subjective happiness and loneliness). Findings show that higher levels of engagement in such Facebook support groups are predicted by the external factors, including having a child, longer duration of membership in the group, family support and the strongest predictor, perception of the group as important. Findings also show that higher levels of engagement in these groups are predicted by internal factors extroversion and openness to experience, as was found in previous studies of other populations. Results and future research are discussed.

Purpose: Optic pathway gliomas (OPG) are low-grade pilocytic astrocytomas accounting for 3-5% of pediatric intracranial tumors. Accurate and quantitative follow-up of OPG using magnetic resonance imaging (MRI) is crucial for therapeutic decision making, yet is challenging due to the complex shape and heterogeneous tissue pattern which characterizes these tumors. The aim of this study was to implement automatic methods for segmentation and classification of OPG and its components, based on MRI., Methods: A total of 202 MRI scans from 29 patients with chiasmatic OPG scanned longitudinally were retrospectively collected and included in this study. Data included T 2 and post-contrast T 1 weighted images. The entire tumor volume and its components were manually annotated by a senior neuro-radiologist, and inter- and intra-rater variability of the entire tumor volume was assessed in a subset of scans. Automatic tumor segmentation was performed using deep-learning method with U-Net+ResNet architecture. A fivefold cross-validation scheme was used to evaluate the automatic results relative to manual segmentation. Voxel-based classification of the tumor into enhanced, non-enhanced, and cystic components was performed using fuzzy c-means clustering., Results: The results of the automatic tumor segmentation were: mean dice score = 0.736 ± 0.025, precision = 0.918 ± 0.014, and recall = 0.635 ± 0.039 for the validation data, and dice score = 0.761 ± 0.011, precision = 0.794 ± 0.028, and recall = 0.742 ± 0.012 for the test data. The accuracy of the voxel-based classification of tumor components was 0.94, with precision = 0.89, 0.97, and 0.85, and recall = 1.00, 0.79, and 0.94 for the non-enhanced, enhanced, and cystic components, respectively., Conclusion: This study presents methods for automatic segmentation of chiasmatic OPG tumors and classification into the different components of the tumor, based on conventional MRI. Automatic quantitative longitudinal assessment of these tumors may improve radiological monitoring, facilitate early detection of disease progression and optimize therapy management., (© 2020 American Association of Physicists in Medicine.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The coronavirus disease 2019 (COVID-19) pandemic has remarkably challenged health care organizations and societies. A key strategy for confronting the disease implications on individuals and communities was based on harnessing multidisciplinary efforts to develop technologies for mitigating the disease spread and its deleterious clinical implications. One of the main challenging characteristics of COVID-19 is the provision of medical care to patients with a highly infective disease mandating the use of isolation measures. Such care is complicated by the need for complex critical care, dynamic treatment guidelines, and a vague knowledge regarding the disease's pathophysiology. A second key component of this challenge was the overwhelming surge in patient burden and the relative lack of trained staff and medical equipment which required rapid re-organization of large systems and augmenting health care efficiencies to unprecedented levels. In contrast to the risk management strategies employed to mitigate other serious threats and the billions of dollars that are invested in reducing these risks annually by governments around the world, no such preparation has been shown to be of effect during the current COVID-19 pandemic. Unmet needs were identified within the newly opened COVID-19 departments together with the urgent need for reliable information for effective decision-making at the state level.This review article describes the early research and development response in Israel under the scope of in-hospital patient care, such as non-contact sensing of patients' vital signs, and how it could potentially be weaved into a practical big picture at the hospital or national level using a strategic management system. At this stage, some of the described technologies are still in developmental or clinical evidence generation phases with respect to COVID-19 settings. While waiting for future publications describing the results of the ongoing evidence generation efforts, one should be aware of this trend as these emerging tools have the potential to further benefit patients as well as caregivers and health care systems beyond the scope of the current pandemic as well as confronting future surges in the number of cases.

Objective: Presurgical memory functional MRI (fMRI) mapping for temporal lobe epilepsy surgery is important because of the excision of structures in the temporal lobe (e.g., hippocampus) that are relevant for intact memory. Although the American Academy of Neurology recommends the use of fMRI for presurgical mapping of epilepsy of verbal and nonverbal memory to predict memory outcome, there are still no specific recommendations about which tests to use. In the current study, we evaluate the potential for clinical utility of two established neuropsychological tests of memory adapted into the fMRI setting., Method: We used the Verbal Paired Associates (VPA) for assessment of verbal memory and the Object Learning and Location (OLL) task for assessment of visuospatial memory. To confirm that these tasks engage the hippocampus, we examined their neural underpinning and patterns of laterality in 20 healthy volunteers (mean age = 26.35)., Results: During fMRI of the VPA task of verbal memory, we found a strong left-lateralized posterior hippocampal activation. Remembering the location of objects in the OLL task of visuospatial memory elicited right-lateralized hippocampal activation., Conclusions: These findings demonstrate the utility of the VPA and OLL tests to delineate domain-specific activity and laterality and, as such, may provide supportive evidence to strengthen links between presurgical neuropsychological assessment and memory fMRI mapping for epilepsy surgery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice.

In this case study, we present a 21 years old female with long-standing Temporal Lobe Epilepsy (TLE) who, following a sexual assault, also developed Posttraumatic Stress Disorder (PTSD), leading to a change in her seizure semiology. The new seizures seemed to be a re-enactment of the sexual assault and accordingly were at first thought to be Psychogenic Non-Epileptic Seizures (PNES). Nevertheless, electroencephalography (EEG) recording at the Epilepsy Monitoring Unit (EMU) revealed ictal epileptic brain activity during these new attacks. In order to further explore the nature of the relation between epileptic seizures and PTSD symptomatology, a functional MRI (fMRI) scan was conducted focusing on neural response to threat (fearful faces). The results indicated that the response to threat elicited bilateral amygdala activation, as well as enhanced amygdala connectivity with the insula and anterior cingulate cortex (ACC), all central nodes of the fear circuitry. Accordingly, we suggest that this unique presentation of "pseudo" PNES might stem from the anatomical proximity of the epileptic network in this patient (temporal-insular-frontal) to the fear circuitry, allowing abnormal epileptic activity to "exploit" or activate the fear circuit or vice versa. We further propose that the traumatic experience may have changed the patient's ictal semiology by modifying the course of the spread of the ictal activity toward the PTSD network., (Copyright © 2020 Biran, Admon, Gazit and Fahoum.)

Objective: Preoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL)., Methods: The study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012-2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods., Results: MSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01)., Conclusions: Both MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

Background: Ruminative responding involves repetitive and passive thinking about one's negative affect. This tendency interferes with initiation of goal-directed rewarding strategies, which could alleviate depressive states. Such reward-directed response selection has been shown to be mediated by ventral striatum/nucleus accumbens (VS/NAcc) function. However, to date, no study has examined whether trait rumination relates to VS/NAcc functionality. Here, we tested whether rumination moderates VS/NAcc function both in response to reward and during a ruminative state., Methods: Trait rumination was considered dimensionally using Rumination Response Scale (RRS) scores. Our sample (N = 80) consisted of individuals from a community sample and from patients diagnosed with major depressive disorder, providing a broad range of RRS scores. Participants underwent fMRI to assess two modes of VS/NAcc functionality: 1) in response to reward, and 2) during resting-state, as a proxy for ruminative state. We then tested for associations between RRS scores and VS/NAcc functional profiles, statistically controlling for overall depressive symptom severity., Results: RRS scores correlated positively with VS/NAcc response to reward. Furthermore, we noted that higher RRS scores were associated with increased ruminative-dependent resting-state functional connectivity of the VS/NAcc with the left orbitofrontal cortex., Conclusions: These findings suggest that ruminative tendencies manifest in VS/NAcc reward- and rumination-related functions, providing support for a theoretical-clinical perspective of rumination as a habitual impairment in selection of rewarding, adaptive coping strategies., (Copyright © 2020 Erdman, Abend, Jalon, Artzi, Gazit, Avirame, Ais, Levokovitz, Gilboa-Schechtman, Hendler and Harel.)

Objective: Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one's mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena., Methods: A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations., Results: In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes., Conclusions: These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

EEG-fMRI allows the localization of the hemodynamic correlates of neural activity and has been shown to be useful as a diagnostic tool in pre-surgical evaluation of refractory epilepsy. However, EEG recordings may be highly contaminated by artifacts induced by movements inside the magnetic field thus rendering the scan difficult for interpretation. Existing methods for motion correction require additional equipment or hardware modification. We introduce a simple method for motion artifact detection, the conductive gel bridge sensor (CGBS), easily applicable using the standard setup. We report examples of CGBS use in two patients with epilepsy and demonstrate the method's ability to successfully differentiate between epochs of brain activity and those of movement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVE Resection of intraaxial tumors adjacent to the optic radiation (OR) may be associated with postoperative visual field (VF) deficits. Intraoperative navigation using MRI-based tractography and electrophysiological monitoring of the visual pathways may allow maximal resection while preserving visual function. In this study, the authors evaluated the value of visual pathway mapping in a series of patients undergoing awake craniotomy for tumor resection. METHODS A retrospective analysis of prospectively collected data was conducted in 18 patients who underwent an awake craniotomy for resection of intraaxial tumors involving or adjacent to the OR. Preoperative MRI-based tractography was used for intraoperative navigation, and intraoperative acquisition of 3D ultrasonography images was performed for real-time imaging and correction of brain shift. Goggles with light-emitting diodes were used as a standard visual stimulus. Direct cortical visual evoked potential (VEP) recording, subcortical recordings from the OR, and subcortical stimulation of the OR were used intraoperatively to assess visual function and proximity of the lesion to the OR. VFs were assessed pre- and postoperatively. RESULTS Baseline cortical VEP recordings were available for 14 patients (77.7%). No association was found between preoperative VF status and baseline presence of cortical VEPs (p = 0.27). Five of the 14 patients (35.7%) who underwent subcortical stimulation of the OR reported seeing phosphenes in the corresponding contralateral VF. There was a positive correlation (r = 0.899, p = 0.04) between the subcortical threshold stimulation intensity (3-11.5 mA) and the distance from the OR. Subcortical recordings from the OR demonstrated a typical VEP waveform in 10 of the 13 evaluated patients (76.9%). These waveforms were present only when recordings were obtained within 10 mm of the OR (p = 0.04). Seven patients (38.9%) had postoperative VF deterioration, and it was associated with a length of < 8 mm between the tumor and the OR (p = 0.05). CONCLUSIONS Intraoperative electrophysiological monitoring of the visual pathways is feasible but may be of limited value in preserving the functional integrity of the posterior visual pathways. Subcortical stimulation of the OR may identify the location of the OR when done in proximity to the pathways, but such proximity may be associated with increased risk of postoperative worsening of the VF deficit.

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Objective: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor., Methods: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy., Results: The SNR achieved by daEEG was 11.05±3.10 and by OBS was 8.25±1.01 (p<0.00001). In 9 of 10 patients, more spikes were detected after daEEG than after OBS (p<0.05)., Significance: daEEG improves signal quality in EEG-fMRI recordings, expanding its clinical and research potential., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Despite progress in elucidating mechanisms of depression, the efficacy of different treatments remains inadequate. Recent small-scale clinical studies suggested anti-depressant treatment using deep brain stimulation (DBS) of the ventral capsule/ventral striatum or subgenual cingulate cortex (SCC), yet controlled, multi-center trials were unsuccessful. We recently suggested the ventral tegmental area (VTA) as an important intersection for treating depression. We also found that stimulation of the VTA of a genetic rat model of depression (Flinders Sensitive Line (FSL) rats) with a programmed pattern designed to mimic the burst firing of normal rats decreases depressive-like behavior. Herein, we examined the possibility of reaching the VTA - located deep in the brain stem - through its direct connection to the ventro-medial prefrontal cortex (vmPFC), which parallels the human SCC. Thus, we compared treatment of FSLs with modified versions of DBS - either chronic-intermittent low-frequency electrical stimulation of the vmPFC, or patterned acute electrical stimulation (pAES), which integrates transcranial magnetic stimulation properties, namely, bursts of pulse trains and low frequency stimulation, applied to the VTA. We found that stimulation of the vmPFC (20Hz, 15min/day, 10days) improved depressive-like behavior and VTA local field potential (LFP) activity of FSLs, yet it had only a partial long-term effect on behavior. In particular, vmPFC stimulation decreased theta band activity, which correlated with the improvement in depressive-like behavior of all treated FSLs at day 1, and in ~50% of treated FSLs at day 28 post treatment. pAES of the VTA (10Hz, 20min) caused significant, long-term improvement of depressive-like behavior of FSLs, concurrently with normalizing intra-VTA LFP activity, and increasing VTA LFP synchronicity and hippocampal BDNF mRNA levels. Thus, although low-frequency electrical stimulation of the PFC alters VTA activity, leading to attenuation of depressive-like manifestations, a specific stimulation pattern affecting VTA cell programming is important for long-term efficacy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

OBJECTIVE Providing a reliable assessment of language lateralization is an important task to be performed prior to neurosurgery in patients with epilepsy. Over the last decade, functional MRI (fMRI) has emerged as a useful noninvasive tool for language lateralization, supplementing or replacing traditional invasive methods. In standard practice, fMRI-based language lateralization is assessed qualitatively by visual inspection of fMRI maps at a specific chosen activation threshold. The purpose of this study was to develop and evaluate a new computational technique for providing the probability of each patient to be left, right, or bilateral dominant in language processing. METHODS In 76 patients with epilepsy, a language lateralization index was calculated using the verb-generation fMRI task over a wide range of activation thresholds (from a permissive threshold, analyzing all brain regions, to a harsh threshold, analyzing only the strongest activations). The data were classified using a probabilistic logistic regression method. RESULTS Concordant results between fMRI and Wada lateralization were observed in 89% of patients. Bilateral and right-dominant groups showed similar fMRI lateralization patterns differentiating them from the left-dominant group but still allowing classification in 82% of patients. CONCLUSIONS These findings present the utility of a semi-supervised probabilistic learning approach for presurgical language-dominance mapping, which may be extended to other cognitive domains such as memory and attention.

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.

Deep brain stimulation (DBS) significantly alleviates symptoms in various neurological disorders. Current research focuses on developing programmed stimulation protocols for customization to individual symptoms. However, the therapeutic mechanism of action of programmed DBS (pDBS) is poorly understood. We previously demonstrated that pDBS in the ventral tegmental area (VTA) normalizes molecular and behavioral abnormalities in the Flinders Sensitive Line (FSL) rat model for depression. Herein, we examined the effect of a short-duration, low-frequency DBS template on local field potential (LFP) synchronization patterns along the anterior-posterior axis of the VTA of FSL rats, and correlation of this effect with depressive-like behavior, as compared with non-programmed, continuous low-frequency DBS (npDBS). We used the wavelet phase coherence (WPC) measure for effective representation of time and frequency of LFP patterns, and the forced swim test to measure immobility (despair). Baseline WPC values were lower in FSLs as compared with SD controls, at the low and high gamma frequency range (above 30 Hz). Baseline immobility scores for FSL rats were higher than those of SD rats, while pDBS, and not npDBS, significantly reduced FSL immobility scores to control SD levels, up to day 14. pDBS also significantly increased the change (between baseline and day 14) in WPC values, in beta, low gamma and high gamma frequency ranges. The change in high gamma (60-100 Hz) WPC values correlated with improvement in depressive-like behavior. Our results suggest that programmed DBS of the VTA increases interaction among local neuronal populations, an effect that may underlie the normalization of depressive-like behavior., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Much effort has been devoted to developing analysis methods of subdural electroencephalogram and depth electrode recordings of epileptic patients being evaluated for surgical resection. The general approach is to investigate the brain activity at different locations as recorded by the different electrodes in an attempt to localize the epileptogenic focus or foci. Currently, most of the methods are based on the notion that epileptogenic brain activity is associated with changes in synchronization and in complexity. Here we present a method that is based on the temporal dynamics combined with the spectral distribution of energy in terms of frequency-entropy (FE) templates. The FE templates are based upon maximum information partitioning into a set of frequency bands. The FE template is calculated by wavelet packet decomposition followed by an application of the best basis algorithm minimizing the entropy cost function. A comparison between two FE templates is performed by a special quantitative similarity measure according to the overlap in the partitioning into frequency bands and weighted by the bands' entropy. For localization of the epileptogenic foci, the templates of each electrode during the interictal period are compared with a representative template evaluated from the ensemble of all electrodes during the ictal period. We suggest associating the locations that reveal high template similarity to the ictal template with the epileptogenic foci. To test the method and the underlying assumptions, we perform retrospective analysis of the recorded brain activity, from both grid and depth electrodes, from 11 patients suffering from medically intractable epilepsy. Application of the ictal-interictal FE template similarity analysis revealed regions in the epileptic brain in which the interictal characteristics are highly similar to those of the ictal period. To asses the foci we compared the interictal templates of the different electrodes to each other, forming interelectrode similarity matrices. Investigation of these similarity matrices revealed the existence of a single distinct subcluster of electrodes with high interelectrode similarity in the brain activity of seven patients (type-I activity), and the existence of multiple high interelectrode similarity subclusters in the activity of four patients (type-II activity). Comparisons of the analysis results to the medical presurgical evaluations and the outcomes of the surgical resections suggest that the method may be helpful in the chronic evaluation of the epileptogenic zone before operation, and in some cases (type-I activity) without the need to wait for seizures to occur.