Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Impact of prenatal cannabis exposure on functional connectivity of the salience network in children.

Cannabis use among pregnant people has increased over the past decade. This is of concern as prenatal cannabis exposure (PCE) is associated with cognitive, motor, and social deficits among offspring. Here, we examined resting-state functional connectivity (rsFC) of the salience network (SN)-a core neurocognitive network that integrates emotional and sensory information-in children with (vs. without) PCE. Using neuroimaging and developmental history data collected from 10,719 children (M ± SD = 9.92 ± 0.62 years; 47.9% female) from the Adolescent Brain Cognitive Development study, we assessed the impact of parent-reported PCE (before or after knowledge of pregnancy) on rsFC within and between the SN and five other core neurocognitive networks. We also evaluated whether SN rsFC mediated the association between PCE and child psychopathology. Results showed that PCE before (but not after) knowledge of pregnancy was associated with lower SN-ventral attention network (VAN) rsFC. Furthermore, psychotic-like experiences mediated the association between PCE and SN-VAN rsFC, and reversal of the model was also significant, such that SN-VAN rsFC mediated the association between PCE and psychotic-like symptoms. However, these mediation effects were no longer significant after the inclusion of covariates. Taken together, these findings suggest that developmental alterations in SN-VAN interactions may explain the previously reported association between PCE and elevated risk of child psychopathology.

Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder.

Failure to successfully extinguish fear is a hallmark of trauma-related disorders, like posttraumatic stress disorder (PTSD). PTSD is also characterized by dysfunctional corticolimbic activation and connectivity. The endocannabinoid system is a putative system to target for rescuing these behavioral and neural deficits. In healthy adults, acute, low-dose delta-9-tetrahydrocannabinol (THC) facilitates fear extinction and increases cortico-limbic activation and connectivity in response to threat. The present study determines the effect of acute, low-dose THC on fear-related brain activation and connectivity during fear extinction in trauma-exposed adults with (PTSD = 19) and without PTSD [trauma-exposed controls (TEC) = 26] and non-trauma-exposed [healthy controls (HC) = 26]. We used a Pavlovian fear conditioning and extinction paradigm, where we measured concurrent functional magnetic resonance imaging (fMRI) and behavioral responses (i.e., skin conductance responding and expectancy ratings). Using a randomized, double-blind, placebo-controlled design, N = 71 subjects were randomized to receive placebo (PBO, n = 37) or THC (n = 34) prior to fear extinction learning. During early extinction learning, individuals with PTSD given THC had greater vmPFC activation than their TEC counterparts. During a test of the return of fear (i.e., renewal), HC and individuals with PTSD given THC had greater vmPFC activation compared to TEC. Individuals with PTSD given THC also had greater amygdala activation compared to those given PBO. We found no effects of trauma group or THC on behavioral fear indices during extinction learning, recall, and fear renewal. These data suggest that low dose, oral THC can affect neural indices of fear learning and memory in adults with trauma-exposure; this may be beneficial for future therapeutic interventions seeking to improve fear extinction learning and memory.

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.

Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive-reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear-related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N = 59; C/C = 35, A-carrier = 24). We found lesser amygdala activation in A-allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A-carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.

Advances in robotic surgery for pediatric ureteropelvic junction obstruction and vesicoureteral reflux: history, present, and future.

PURPOSE: The introduction of robotic surgical technology into urological reconstruction, particularly pediatrics, has introduced new horizons for reducing the morbidity and enhancing the efficacy of surgical repair of congenital conditions in children. In reviewing the evolution of pediatric urological applications of robotic surgery, we wanted to address the different levels of reported utilization of pyeloplasty and ureteral reimplantation as two of the most common procedures. METHODS: Review of the published literature sought to explore the described variation in clinical application of these two common procedures, and the evolution of the practice over time. RESULTS: Reported outcomes suggest that variations in patient selection, the learning curve and in reporting of outcomes all contribute to the wide variation in utilization of pediatric robotic pyeloplasty and ureteral reimplantation. CONCLUSIONS: These technologies are demonstrating their potential as well as the challenges of use in children and there is a steady evolution of capability. Practitioners should be aware of both the possibilities as well as the risks of such new technology in the care of our patients. This requires thorough and open reporting of outcomes, the willingness to introduce change and integrate new findings into practice.

Community and household-level socioeconomic disadvantage and functional organization of the salience and emotion network in children and adolescents.

Socioeconomic disadvantage (SED) during childhood has been linked to disparities in physical and mental health. A growing body of research has focused on identifying neurodevelopmental consequences of SED, commonly measured using within-household factors (e.g., household income), to better understand the processes underlying SED-related disparities. These studies suggest that childhood SED has a widespread impact on brain development, altering development of multiple brain regions simultaneously. These findings also raise the possibility that childhood SED impacts development of key brain systems, such as the salience and emotion network (SEN), which is positioned at the intersection of brain systems involved in cognitive and emotion-related functioning and is thought to mediate information flow within and between these networks. The present study tests for associations between household- and community-level SED, as well as their interaction, and measures of SEN-based functional neural organization in 57 children and adolescents (ages 6-17). We applied graph theoretical analyses to resting-state functional magnetic resonance imaging (fMRI) data to examine SEN-based functional network topology. Results showed that youth residing in more distressed communities demonstrate lower hub-like properties (i.e., less efficient global information transfer and fewer connections) of two core SEN nodes - the anterior cingulate cortex and the left supramarginal gyrus. Similarly, lower household income was associated with lower efficiency of the anterior cingulate, but had no effect on the supramarginal gyrus. There was, however, an interaction between income and community SED in the rostral prefrontal cortex, such that higher income was associated with higher clustering coefficient and lower betweenness centrality, suggesting greater local processing and lower influence of this region on information flow across the network. These effects were significant only among youth living in low (but not high) SED communities, suggesting that within-household SED factors may not protect against the detrimental effects of a disadvantaged community context. Similarly, the age-related increase in average path length of the left rostral prefrontal cortex was only significant among youth living in low (but not high) SED communities. Given that maturation of the SEN is considered to be a critical functional backbone supporting the development of more flexible cognitive and emotional processes into adulthood, we tested for links between SEN graph metrics and measures of cognitive and emotion-related functioning. We found that higher community SED and lower income were both associated with lower IQ. Lower IQ, in turn, was associated with global efficiency of the left supramarginal gyrus. Observed effects of SED on SEN-based functional neural organization may help to explain the strong and pervasive link between childhood SED and disparities in cognitive and emotional outcomes.

Emotion-related brain organization and behavioral responses to socioemotional stimuli in pediatric cancer survivors with posttraumatic stress symptoms.

BACKGROUND: Pediatric cancer is a life-changing, stressful experience for children and their families. Although most children adjust well, psychologically, a significant subset report posttraumatic stress symptoms (PTSS), with nearly 75% reexperiencing traumatic parts of cancer and/or its treatment. However, little research has examined the effects of pediatric cancer and related PTSS on emotional processing, and on functional properties of key emotional centers in the brain (e.g., amygdala). PROCEDURE: We examined cancer-related PTSS, behavioral responses during an emotion-processing task, and resting-state functional connectivity of the amygdala in 17 pediatric cancer survivors (ages 6-11) and 17 age- and sex-matched controls. RESULTS: Cancer survivors, relative to controls, were more likely to rate ambiguous (i.e., neutral) faces as negative (i.e., "negativity bias"). Higher reexperiencing PTSS was associated with faster responses to neutral faces. Although there were no group differences in amygdala centrality, within survivors, both higher reexperiencing PTSS and faster reaction times were associated with increased centrality of the amygdala-a functional property associated with hubs of information processing in the brain. In an exploratory mediation analysis, we found that amygdala centrality mediated the link between reaction time and PTSS, suggesting that changes in the brain may be a proximal marker of the expression of emotion-related symptomology. CONCLUSIONS: Negativity bias in cancer survivors may reflect their stressful experiences with cancer and/or its treatment. This negativity bias may represent a susceptibility to changes in emotion-related brain functioning, which may, in turn, lead to PTSS.

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

BACKGROUND: In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g., anxiety, posttraumatic stress disorder). Despite the early age of onset of virtually all fear-based disorders and the protracted development of the hippocampus and vmPFC across the first two decades of life, little is known about extinction recall and the underlying neural correlates in children. METHODS: Here, we tested extinction recall in 43 pre-adolescent children (ages 6-11 yrs) by coupling functional magnetic resonance imaging and virtual reality with a novel interpersonal threat-related two-day (ABBA) fear-extinction paradigm. Conditioned fear responding was assessed at behavioral, subjective, physiological, and neural levels. RESULTS: Although children demonstrated intact within-session extinction, there was poor between-session recall of extinction learning (retention index: 13.56%), evidenced by elevations in skin conductance, avoidant behavioral responses, and subjective ratings. Elevations in conditioning fear responding were accompanied by activation in the hippocampus and insula, and increased connectivity of the hippocampus with the insula and dorsal anterior cingulate cortex - regions implicated in the return of fear in adult studies. Children who kept more distance from the extinguished cue during extinction subsequently demonstrated heightened hippocampal-cingulate coupling during recall, suggesting that avoidant behavior interferes with extinction retention. CONCLUSIONS: Poor extinction recall in children may have implications for developmental vulnerability to fear-based disorders, and for the application of therapeutic strategies that rely on principles of extinction (e.g., exposure therapy) to pediatric samples.

Current status of robotic-assisted surgery for the treatment of vesicoureteral reflux in children.

PURPOSE OF REVIEW: Although open ureteral reimplantation remains the gold standard for surgical correction of vesicoureteral reflux (VUR), robotic-assisted laparoscopic ureteral reimplantation (RALUR) holds promise and is becoming more widely utilized. The present article outlines primary operative techniques for RALUR, summarizes the current literature with respect to surgical outcomes and costs, and discusses early applications of RALUR to complex and reoperative cases. RECENT FINDINGS: Intravesical and extravesical techniques for RALUR have been described. Published outcomes vary with respect to operational definitions of surgical success and reporting of complications. Several studies have directly compared RALUR and open reimplant, suggesting equivalent efficacy and safety. Recent noncomparative studies have reported lower VUR resolution rates and higher complication rates for RALUR, particularly in bilateral cases. The application of RALUR to reoperative surgery and cases requiring tapering and dismemberment is under very early investigation. RALUR is consistently associated with lower postoperative analgesic requirements and decreased hospital stay, but longer operative times and higher costs compared to open reimplant. SUMMARY: Published outcomes after RALUR show mixed results that, on average, may be inferior to open reimplant. Future investigations should seek to identify patient-related and intraoperative factors associated with successful and unsuccessful outcomes.

Quantitative Ultrasound for Measuring Obstructive Severity in Children with Hydronephrosis.

PURPOSE: We define sonographic biomarkers for hydronephrotic renal units that can predict the necessity of diuretic nuclear renography. MATERIALS AND METHODS: We selected a cohort of 50 consecutive patients with hydronephrosis of varying severity in whom 2-dimensional sonography and diuretic mercaptoacetyltriglycine renography had been performed. A total of 131 morphological parameters were computed using quantitative image analysis algorithms. Machine learning techniques were then applied to identify ultrasound based safety thresholds that agreed with the t½ for washout. A best fit model was then derived for each threshold level of t½ that would be clinically relevant at 20, 30 and 40 minutes. Receiver operating characteristic curve analysis was performed. Sensitivity, specificity and area under the receiver operating characteristic curve were determined. Improvement obtained by the quantitative imaging method compared to the Society for Fetal Urology grading system and the hydronephrosis index was statistically verified. RESULTS: For the 3 thresholds considered and at 100% sensitivity the specificities of the quantitative imaging method were 94%, 70% and 74%, respectively. Corresponding area under the receiver operating characteristic curve values were 0.98, 0.94 and 0.94, respectively. Improvement obtained by the quantitative imaging method over the Society for Fetal Urology grade and hydronephrosis index was statistically significant (p <0.05 in all cases). CONCLUSIONS: Quantitative imaging analysis of renal sonograms in children with hydronephrosis can identify thresholds of clinically significant washout times with 100% sensitivity to decrease the number of diuretic renograms in up to 62% of children.

Robotic natural orifice transluminal endoscopic surgery (R-NOTES): literature review and prototype system.

In minimally invasive surgery methods such as laparoscopic surgery, surgical instruments are introduced through small incisions to minimize patient trauma and recovery times. To reduce the number of incisions, new techniques such as natural orifice transluminal endoscopic surgery (NOTES) have been proposed. Compared to laparoscopic surgery, the NOTES approach, which requires new technology and improved instruments, presents some unique challenges. Robotic NOTES (R-NOTES) could be an enabling technology for these procedures. In this paper, we first review relevant work in R-NOTES. We then present our work and the system architecture for an R-NOTES prototype system incorporating wireless command and control. The system was tested twice in swine animal studies.

Evaluation of prenatal hydronephrosis: novel criteria for predicting vesicoureteral reflux on ultrasonography.

PURPOSE: Radiographic evaluation for prenatal hydronephrosis often includes voiding cystourethrography to ascertain whether vesicoureteral reflux is present. We sought to determine whether use of voiding cystourethrography could be limited to those patients at greatest risk for vesicoureteral reflux. We hypothesized that vesicoureteral reflux could be predicted by findings on renal/bladder ultrasonography of hydroureter, renal dysmorphia and/or duplication. MATERIALS AND METHODS: We reviewed the records of patients with prenatal hydronephrosis who underwent initial postnatal ultrasonography and voiding cystourethrography during a 3-year period. The presence of vesicoureteral reflux on voiding cystourethrogram was correlated to ultrasound findings, including hydronephrosis grade, presence of hydroureter, renal dysmorphia or duplication, with ultrasound considered positive for any of the latter 3 findings. RESULTS: Of 262 patients 47 (18%) had vesicoureteral reflux. Ultrasound was positive in 24 of 29 patients (83%) with high grade reflux and 12 of 18 (67%) with low grade reflux. If ultrasonography showed any of the 3 positive findings, the odds ratio of detecting vesicoureteral reflux was 8.07 (95% CI 3.86, 16.87). Using these criteria, among all cases of prenatal hydronephrosis 5 (2%) with high grade vesicoureteral reflux and 6 (2%) with low grade reflux would have been missed. Among the 47 cases of reflux overall 5 of 29 high grade (17%) and 6 of 18 low grade cases (33%) would have been missed. CONCLUSIONS: By using ultrasonography criteria of hydroureter, duplication and renal dysmorphia for patients with prenatal hydronephrosis, vesicoureteral reflux can be detected more specifically. Using our criteria, 165 of 262 voiding cystourethrograms (63%) could have been avoided in patients with prenatal hydronephrosis during a 3-year period. Reducing these evaluations may decrease risks regarding radiation exposure, family anxiety and health care costs.

Most infants with dilating vesicoureteral reflux can be treated nonoperatively.

PURPOSE: Dilating vesicoureteral reflux provokes concern for physicians and parents that often leads to corrective surgery in young children. Since there are limited data describing the natural history of dilating vesicoureteral reflux in infants, we identified factors predictive of resolution/improvement in infants initially treated nonoperatively. MATERIALS AND METHODS: We reviewed the medical records of 90 infants 6 months old or younger from 2004 to 2010 who were referred for prenatal hydronephrosis or initial febrile urinary tract infection and found to have dilating vesicoureteral reflux (grade 3 or greater). Variables of interest included presentation, dimercapto-succinic acid results, sex, breakthrough febrile urinary tract infections, reflux grade and bilateral reflux. Cox regression analysis was performed to determine predictors of spontaneous resolution and/or improvement to reflux grade less than 3 as well as predictors of surgical intervention. RESULTS: Included in final analysis were 80 infants (113 renal units). Of the patients 51 (64%) experienced spontaneous resolution/improvement with a mean followup of 29 months before resolution, discharge home and/or end of followup. Only 20 patients (25%) underwent surgery. Cox regression analysis revealed that a normal initial dimercapto-succinic acid scan, initial reflux grade less than 5 and absent breakthrough febrile urinary tract infections were predictive of reflux resolution/improvement (p <0.05). Dimercapto-succinic acid scan abnormalities, prenatal hydronephrosis and breakthrough febrile urinary tract infections were significant predictors of surgery (p <0.05). CONCLUSIONS: Dilating vesicoureteral reflux in infancy often resolves/improves spontaneously. Therefore, surgery should be directed toward patients unlikely to experience resolution, ie those with an abnormal initial dimercapto-succinic acid scan, grade 5 vesicoureteral reflux and breakthrough febrile urinary tract infections.

Stereoscopic augmented reality for laparoscopic surgery.

BACKGROUND: Conventional laparoscopes provide a flat representation of the three-dimensional (3D) operating field and are incapable of visualizing internal structures located beneath visible organ surfaces. Computed tomography (CT) and magnetic resonance (MR) images are difficult to fuse in real time with laparoscopic views due to the deformable nature of soft-tissue organs. Utilizing emerging camera technology, we have developed a real-time stereoscopic augmented-reality (AR) system for laparoscopic surgery by merging live laparoscopic ultrasound (LUS) with stereoscopic video. The system creates two new visual cues: (1) perception of true depth with improved understanding of 3D spatial relationships among anatomical structures, and (2) visualization of critical internal structures along with a more comprehensive visualization of the operating field. METHODS: The stereoscopic AR system has been designed for near-term clinical translation with seamless integration into the existing surgical workflow. It is composed of a stereoscopic vision system, a LUS system, and an optical tracker. Specialized software processes streams of imaging data from the tracked devices and registers those in real time. The resulting two ultrasound-augmented video streams (one for the left and one for the right eye) give a live stereoscopic AR view of the operating field. The team conducted a series of stereoscopic AR interrogations of the liver, gallbladder, biliary tree, and kidneys in two swine. RESULTS: The preclinical studies demonstrated the feasibility of the stereoscopic AR system during in vivo procedures. Major internal structures could be easily identified. The system exhibited unobservable latency with acceptable image-to-video registration accuracy. CONCLUSIONS: We presented the first in vivo use of a complete system with stereoscopic AR visualization capability. This new capability introduces new visual cues and enhances visualization of the surgical anatomy. The system shows promise to improve the precision and expand the capacity of minimally invasive laparoscopic surgeries.

Emergent robot-to-open conversion - Multidisciplinary simulation training in crisis management.

Anticipating and addressing unexpected intraoperative events and anatomies are some of the most challenging aspects of pediatric urologic practice; uncontrolled hemorrhage is one of the most anxiety provoking and precarious. The increasing application of the robotic platform in pediatric urology adds another layer of complexity as surgeons are not immediately at the patient's bedside. Should hemorrhage occur in robotic cases, clear communication and seamless coordination between members of the operating room team are paramount to optimize patient safety and minimize errors. This is especially important in pediatric cases for which the margin of error is narrow. Non-technical skills, including leadership, decision-making, situational awareness, stress management, and team-communication, become increasingly critical. While many programs have focused on robotic training, few prepare the operating room team and surgical trainees to manage these unforeseen, emergent intraoperative scenarios. This review discusses the role of a multidisciplinary, in situ robot-to-open conversion simulation program in addressing this educational gap, ways to approach establishing these programs, and potential barriers.

ACR Appropriateness Criteria® Urinary Tract Infection-Child: 2023 Update.

Urinary tract infection (UTI) is a frequent infection in childhood. The diagnosis is usually made by history and physical examination and confirmed by urine analysis. Cystitis is infection or inflammation confined to the bladder, whereas pyelonephritis is infection or inflammation of kidneys. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. This document provides initial imaging guidelines for children presenting with first febrile UTI with appropriate response to medical management, atypical or recurrent febrile UTI, and follow-up imaging for children with established vesicoureteral reflux. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Testicular relapse of acute lymphoblastic leukemia.

Contemporary chemotherapy regimens have led to improved survival and decreased incidence of testicular relapse for pediatric patients with acute lymphoblastic leukemia (ALL). Local therapies to the testes, such as radiotherapy and orchiectomy, are often not necessary given that high-dose chemotherapy agents can overcome the relative blood-testis barrier. However, urologists should be aware of clinical scenarios involving ALL which still warrant testicular biopsy to guide management. Here, we present a case of a 12-year-old boy with high-risk pre-B cell ALL presenting with a testicular relapse and a clinical presentation overlapping with non-infectious epididymo-orchitis.

Granular cell tumor in the scrotum of a pediatric patient: A case report of a rare clinical entity.

Granular cell tumors are rare tumors of Schwann cell origin that present in any anatomic location, age or sex. We present a case of a granular cell tumor in the scrotum of a prepubescent male. The tumor was excised, with histology revealing abundant eosinophilic cytoplasm and positive S-100 staining. No stigmata of malignancy were identified and no recurrence has been reported during follow-up.