Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons.

The precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory are not fully understood. Two-photon calcium imaging allows the activity of individual cells to be followed across long periods, but conventional approaches require head-fixation, which limits the type of behavior that can be studied. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous systems that used mechanical restraint, there are no moving parts and animals can engage and disengage entirely at will. This system is failsafe, easy for animals to use and reliable enough to allow long-term experiments to be routinely performed. Animals completed hundreds of trials per session of an odor discrimination task that required 2-4 s fixations. Together with a reflectance fluorescence collection scheme that increases two-photon signal and a transgenic Thy1-GCaMP6f rat line, we are able to reliably image the cellular activity in the hippocampus during behavior over long periods (median 6 months), allowing us track the same neurons over a large fraction of animals' lives (up to 19 months).

A cross-species framework for investigating perceptual evidence accumulation.

Cross-species studies are important for a comprehensive understanding of brain functions. However, direct quantitative comparison of behaviors across species presents a significant challenge. To enable such comparisons in perceptual decision-making, we developed a synchronized evidence accumulation task for rodents and humans, by aligning mechanics, stimuli, and training. Rats, mice and humans readily learned the task and exhibited qualitatively similar performance. Quantitative model comparison revealed that all three species employed an evidence accumulation strategy, but differed in speed, accuracy, and key decision parameters. Human performance prioritized accuracy, whereas rodent performance was limited by internal time-pressure. Rats optimized reward rate, while mice appeared to switch between evidence accumulation and other strategies trial-to-trial. Together, these results reveal striking similarities and species-specific priorities in decision-making. Furthermore, the synchronized behavioral framework we present may facilitate future studies involving cross-species comparisons, such as evaluating the face validity of animal models of neuropsychiatric disorders. Highlights: Development of a free response evidence accumulation task for rats and miceSynchronized video game allows direct comparisons with humansRat, mouse and human behavior are well fit by the same decision modelsModel parameters reveal species-specific priorities in accumulation strategy.

In vivo imaging in transgenic songbirds reveals superdiffusive neuron migration in the adult brain.

Neuron migration is a key phase of neurogenesis, critical for the assembly and function of neuronal circuits. In songbirds, this process continues throughout life, but how these newborn neurons disperse through the adult brain is unclear. We address this question using in vivo two-photon imaging in transgenic zebra finches that express GFP in young neurons and other cell types. In juvenile and adult birds, migratory cells are present at a high density, travel in all directions, and make frequent course changes. Notably, these dynamic migration patterns are well fit by a superdiffusive model. Simulations reveal that these superdiffusive dynamics are sufficient to disperse new neurons throughout the song nucleus HVC. These results suggest that superdiffusive migration may underlie the formation and maintenance of nuclear brain structures in the postnatal brain and indicate that transgenic songbirds are a useful resource for future studies into the mechanisms of adult neurogenesis.

Advances in cellular resolution microscopy for brain imaging in rats.

Rats are used in neuroscience research because of their physiological similarities with humans and accessibility as model organisms, trainability, and behavioral repertoire. In particular, rats perform a wide range of sophisticated social, cognitive, motor, and learning behaviors within the contexts of both naturalistic and laboratory environments. Further progress in neuroscience can be facilitated by using advanced imaging methods to measure the complex neural and physiological processes during behavior in rats. However, compared with the mouse, the rat nervous system offers a set of challenges, such as larger brain size, decreased neuron density, and difficulty with head restraint. Here, we review recent advances in in vivo imaging techniques in rats with a special focus on open-source solutions for calcium imaging. Finally, we provide suggestions for both users and developers of in vivo imaging systems for rats.

Rat movements reflect internal decision dynamics in an evidence accumulation task.

Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting on-going decision processes occur before commitment to a choice. Here we develop and apply two complementary methods to study the relationship between decision processes and the movements leading up to a choice. The first is a free response pulse-based evidence accumulation task, in which stimuli continue until choice is reported. The second is a motion-based drift diffusion model (mDDM), in which movement variables from video pose estimation constrain decision parameters on a trial-by-trial basis. We find the mDDM provides a better model fit to rats' decisions in the free response accumulation task than traditional DDM models. Interestingly, on each trial we observed a period of time, prior to choice, that was characterized by head immobility. The length of this period was positively correlated with the rats' decision bounds and stimuli presented during this period had the greatest impact on choice. Together these results support a model in which internal decision dynamics are reflected in movements and demonstrate that inclusion of movement parameters improves the performance of diffusion-to-bound decision models.

Quantifying the Prognostic Value of Preoperative Surgeon Intuition: Comparing Surgeon Intuition and Clinical Risk Prediction as Derived from the American College of Surgeons NSQIP Risk Calculator.

BACKGROUND: Surgical risk prediction models traditionally use patient attributes and measures of physiology to generate predictions about postoperative outcomes. However, the surgeon's assessment of the patient may be a valuable predictor, given the surgeon's ability to detect and incorporate factors that existing models cannot capture. We compare the predictive utility of surgeon intuition and a risk calculator derived from the American College of Surgeons (ACS) NSQIP. STUDY DESIGN: From January 10, 2021 to January 9, 2022, surgeons were surveyed immediately before performing surgery to assess their perception of a patient's risk of developing any postoperative complication. Clinical data were abstracted from ACS NSQIP. Both sources of data were independently used to build models to predict the likelihood of a patient experiencing any 30-day postoperative complication as defined by ACS NSQIP. RESULTS: Preoperative surgeon assessment was obtained for 216 patients. NSQIP data were available for 9,182 patients who underwent general surgery (January 1, 2017 to January 9, 2022). A binomial regression model trained on clinical data alone had an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI 0.80 to 0.85) in predicting any complication. A model trained on only preoperative surgeon intuition had an AUC of 0.70 (95% CI 0.63 to 0.78). A model trained on surgeon intuition and a subset of clinical predictors had an AUC of 0.83 (95% CI 0.77 to 0.89). CONCLUSIONS: Preoperative surgeon intuition alone is an independent predictor of patient outcomes; however, a risk calculator derived from ACS NSQIP is a more robust predictor of postoperative complication. Combining intuition and clinical data did not strengthen prediction.

Light-Activated Vascular Anastomosis.

Background. There have been few advances in technique since vascular anastomosis was performed with silk suture on a curved needle in 1902. This technique results in disruption of the endothelium with exposed intraluminal suture, both of which may lead to thrombocyte aggregation, intimal hyperplasia, and vascular stenosis. A variety of alternative techniques have been explored, with limited success. Photochemical tissue bonding (PTB) is a light-activated methodology of rapidly cross-linking tissue interfaces at the molecular level. Herein, we describe a new technique for anastomosis of venous interposition graft in an ovine model of femoral artery bypass utilizing PTB. Methods. Polypay specific pathogen free sheep (n = 5; 40-45 kg) underwent femoral artery bypass utilizing saphenous vein. The femoral artery was transected and reversed saphenous vein was implanted as an interposition graft. The proximal anastomosis was created as a vein-over-artery cuff utilizing PTB, and the distal anastomosis was created with standard interrupted 8-0 polypropylene suture. Four weeks post-index operation, femoral angiogram was performed to evaluate patency, tortuosity, and luminal diameter. All bypass grafts were harvested and longitudinal and transverse histological sections from the proximal anastomosis were analyzed. Results. The PTB anastomoses (n = 5) were immediately watertight and patent. All animals survived the 28-day study duration. Angiography revealed patent grafts with no aneurysm or stenosis (n = 5). Histologic examination revealed integration of the venous endothelium with the arterial adventitia. Conclusion. Photochemical tissue bonding creates an immediate strong, watertight vascular anastomosis that can withstand physiologic arterial pressure and remains patent at 28 days without the need for intraluminal suture.

Assessing evidence accumulation and rule learning in humans with an online game.

Evidence accumulation, an essential component of perception and decision making, is frequently studied with psychophysical tasks involving noisy or ambiguous stimuli. In these tasks, participants typically receive verbal or written instructions that describe the strategy that should be used to guide decisions. Although convenient and effective, explicit instructions can influence learning and decision making strategies and can limit comparisons with animal models, in which behaviors are reinforced through feedback. Here, we developed an online video game and nonverbal training pipeline, inspired by pulse-based tasks for rodents, as an alternative to traditional psychophysical tasks used to study evidence accumulation. Using this game, we collected behavioral data from hundreds of participants trained with an explicit description of the decision rule or with experiential feedback. Participants trained with feedback alone learned the game rules rapidly and used strategies and displayed biases similar to those who received explicit instructions. Finally, by leveraging data across hundreds of participants, we show that perceptual judgments were well described by an accumulation process in which noise scaled nonlinearly with evidence, consistent with previous animal studies but inconsistent with diffusion models widely used to describe perceptual decisions in humans. These results challenge the conventional description of the accumulation process and suggest that online games provide a valuable platform to examine perceptual decision making and learning in humans. In addition, the feedback-based training pipeline developed for this game may be useful for evaluating perceptual decision making in human populations with difficulty following verbal instructions.NEW & NOTEWORTHY Perceptual uncertainty sets critical constraints on our ability to accumulate evidence and make decisions; however, its sources remain unclear. We developed a video game, and feedback-based training pipeline, to study uncertainty during decision making. Leveraging choices from hundreds of subjects, we demonstrate that human choices are inconsistent with popular diffusion models of human decision making and instead are best fit by models in which perceptual uncertainty scales nonlinearly with the strength of sensory evidence.

Everything, everywhere, all at once: Functional specialization and distributed coding in the cerebral cortex.

In this issue of Neuron, Tseng and colleagues reveal functional gradients in the mouse posterior cortex that reconcile specialized and distributed processing during flexible, goal-directed navigation.

Surgical Approaches for Prevention of Neuroma at Time of Peripheral Nerve Injury.

Painful neuroma is a frequent sequela of peripheral nerve injury which can result in pain and decreased quality of life for the patient, often necessitating surgical intervention. End neuromas are benign neural tumors that commonly form after nerve transection, when axons from the proximal nerve stump regenerate in a disorganized manner in an attempt to recreate nerve continuity. Inflammation and collagen remodeling leads to a bulbous end neuroma which can become symptomatic and result in decreased quality of life. This review covers surgical prophylaxis of end neuroma formation at time of injury, rather than treatment of existing neuroma and prevention of recurrence. The current accepted methods to prevent end neuroma formation at time of injury include different mechanisms to inhibit the regenerative response or provide a conduit for organized regrowth, with mixed results. Approaches include proximal nerve stump capping, nerve implantation into bone, muscle and vein, various pharmacologic methods to inhibit axonal growth, and mechanisms to guide axonal growth after injury. This article reviews historical treatments that aimed to prevent end neuroma formation as well as current and experimental treatments, and seeks to provide a concise, comprehensive resource for current and future therapies aimed at preventing neuroma formation.

GraFT: Graph Filtered Temporal Dictionary Learning for Functional Neural Imaging.

Optical imaging of calcium signals in the brain has enabled researchers to observe the activity of hundreds-to-thousands of individual neurons simultaneously. Current methods predominantly use morphological information, typically focusing on expected shapes of cell bodies, to better identify neurons in the field-of-view. The explicit shape constraints limit the applicability of automated cell identification to other important imaging scales with more complex morphologies, e.g., dendritic or widefield imaging. Specifically, fluorescing components may be broken up, incompletely found, or merged in ways that do not accurately describe the underlying neural activity. Here we present Graph Filtered Temporal Dictionary (GraFT), a new approach that frames the problem of isolating independent fluorescing components as a dictionary learning problem. Specifically, we focus on the time-traces-the main quantity used in scientific discovery-and learn a time trace dictionary with the spatial maps acting as the presence coefficients encoding which pixels the time-traces are active in. Furthermore, we present a novel graph filtering model which redefines connectivity between pixels in terms of their shared temporal activity, rather than spatial proximity. This model greatly eases the ability of our method to handle data with complex non-local spatial structure. We demonstrate important properties of our method, such as robustness to morphology, simultaneously detecting different neuronal types, and implicitly inferring number of neurons, on both synthetic data and real data examples. Specifically, we demonstrate applications of our method to calcium imaging both at the dendritic, somatic, and widefield scales.

A Photosealed Cap Prevents Disorganized Axonal Regeneration and Neuroma following Nerve Transection in Rats.

Neuroma is a common sequela of traumatic peripheral nerve injury that can result in pain and decreased quality of life for patients. Neuromas result from axonal outgrowth in an attempt to reestablish continuity with the disrupted distal nerve end. Photosealing is a light-activated technique whereby tissues can be securely isolated in a strong and secure manner. This study investigated whether photosealing of autologous vein and crosslinked human amniotic membrane (xHAM) to cap the proximal stump of transected sciatic nerve would prevent disorganized axonal regeneration and neuroma in a rat model. Methods: The right sciatic nerve of Lewis rats (n = 27, 300-350 g) was transected 1 cm proximal to the trifurcation. Animals were randomized to one of three groups (n = 9): no further intervention (Group 1), photosealing with xHAM (Group 2), or photosealing with vein (Group 3). After 60 days, rats were euthanized and their right hindlimbs were re-explored for evidence of disorganized axonal regeneration and/or bulbous neuroma. Results: All untreated control animals were found to have protruding nerve fibers, often invading the adjacent muscle, and 33% of these control animals exhibited a bulbous neuroma. Photosealing with xHAM successfully capped 100% of nerves, with no observable axonal outgrowth. Photosealing with vein prevented axonal outgrowth in eight of nine nerves. No bulbous neuroma was found in any photosealed nerves. Conclusion: Nerve capping with photosealed xHAM or autologous vein can prevent axonal outgrowth in transected nerves, therefore decreasing the likelihood of symptomatic neuroma formation following nerve transection injury or surgical intervention.

Light-activated photosealing with human amniotic membrane strengthens bowel anastomosis in a hypotensive, trauma-relevant swine model.

BACKGROUND: Gastrointestinal anastomotic leakage is a dreaded complication despite advancements in surgical technique. Photochemical tissue bonding (PTB) is a method of sealing tissue surfaces utilizing photoactive dye. We evaluated if crosslinked human amniotic membrane (xHAM) photosealed over the enteroenterostomy would augment anastomotic strength in a trauma-relevant swine hemorrhagic shock model. METHODS: Yorkshire swine (40-45 kg, n = 14) underwent midline laparotomy and sharp transection of the small intestine 120 cm proximal to the ileocecal fold. Immediately following intestinal transection, a controlled arterial bleed was performed to reach hemorrhagic shock. Intestinal repair was performed after 60 minutes and autotransfusion of the withdrawn blood was performed for resuscitation. Animals were randomized to small intestinal anastomosis by one of the following methods (seven per group): suture repair (SR), or SR with PTB augmentation. Animals were euthanized at postoperative Day 28 and burst pressure (BP) strength testing was performed on all excised specimens. RESULTS: Mean BP for SR, PTB, and native tissue groups were 229 ± 40, 282 ± 21, and 282 ± 47 mmHg, respectively, with the SR group statistically significantly different on analysis of variance (p = 0.02). Post-hoc Tukey all-pairs comparison demonstrated a statistically significant difference in burst pressure strength between the SR only and the PTB group (p = 0.04). All specimens in SR group ruptured at the anastomosis upon burst pressure testing, while all specimens in the PTB group ruptured at least 2.5 cm from the anastomosis. CONCLUSION: Photosealing with xHAM significantly augments the strength of small intestinal anastomosis performed in a trauma porcine model.

Readability and Understandability Analysis of Online Materials Related to Abdominal Aortic Aneurysm Repair.

BACKGROUND: Patients commonly use online materials as a source of health information. Since poor health literacy has been shown to correlate with negative outcomes, it is recommended that patient-directed materials be written at a sixth-grade reading level. This study evaluates the readability and understandability of commonly accessed online materials pertaining to both endovascular and open repair of abdominal aortic aneurysm. METHODS: Searches for "endovascular repair abdominal aortic aneurysm" and "open repair abdominal aortic aneurysm" were performed on both Google and Bing, and the top 10 websites from each search engine were identified. Relevant websites (total N = 28, endovascular n = 15, open n = 15, and 2 redundant sites) with patient-directed content were analyzed. Readability was assessed using 9 established methods, and understandability was assessed using the Patient Education Materials Assessment Tool scoring system. RESULTS: The average reading grade level for all sites was 12.8. Endovascular sites averaged a reading grade level of 13.6 with a range from 11.5 to 15.6. Open-repair websites had a grade-level average of 12.1 with a range from 9.9 to 14.1. Readability was found to be inversely related to understandability, with a Pearson correlation coefficient of -0.551 (P = .003). No website was written at or below the recommended sixth-grade reading level. CONCLUSIONS: Patient-directed online health information pertaining to open and endovascular repair of abdominal aortic aneurysm exceeds the recommended sixth-grade reading level. Increasing complexity of health literature correlates with poor understandability. Modifications such as shorter sentences, fewer words with more than 6 letters, and increasing usage of clear visual aids can increase readability and understandability.

Gallbladder volvulus in a patient with chronic lymphocytic leukemia treated with laparoscopic cholecystectomy.

Gallbladder volvulus is a rare condition that most commonly occurs in elderly women and often mimics acute cholecystitis in its presentation. This condition is a surgical emergency requiring cholecystectomy as it can lead to gallbladder perforation and bilious peritonitis with high morbidity to the patient. An 85-year-old woman with chronic lymphocytic leukemia presented with acute-onset right upper-quadrant abdominal pain and associated nausea with emesis. After admission to the surgical service and initiation of intravenous antibiotics, the patient was taken to the operating room for surgical management due to the persistence of symptoms. Intraoperative findings included a necrotic appearing gallbladder that was twisted on the cystic duct. Laparoscopic cholecystectomy was performed, which was complicated by bile leak requiring endoscopic retrograde cholangiopancreatography with bile duct stenting followed by operative washout. Gallbladder volvulus can be challenging to diagnose. This condition should be suspected in elderly women with acute-onset abdominal pain and imaging concerning for acute cholecystitis. Emergent cholecystectomy is the treatment of choice for gallbladder volvulus.

Robot-Assisted Thoracoscopic Mediastinal Parathyroidectomy: A Single Surgeon Case Series.

Objective: Minimally invasive (video-assisted thoracoscopic surgery) mediastinal parathyroidectomy has been described as a technique for surgical management of primary hyperparathyroidism due to ectopic parathyroid adenoma. Herein, we present the largest cohort of patients (n = 8) treated with robot-assisted mediastinal parathyroidectomy and describe our technique for this procedure, pre- and intraoperative variables, and postoperative outcomes. Materials and Methods: A single surgeon, single institution case series of eight consecutive robot-assisted mediastinal parathyroidectomies performed from April 2013 to March 2018. Preoperative workup, intraoperative variables, and postoperative outcomes were evaluated. Results: Of the eight patients, seven were women. Average age was 54 years (range: 28-69) and average body mass index 33.6 (range: 24.8-42.9). Seven patients had a preoperative diagnosis of primary hyperparathyroidism with preoperative parathyroid hormone (PTH) and calcium levels (PTH: 137 (70-192); Ca2+: 10.9 (10.2-12), and one patient had preoperative diagnosis of thymoma. Preoperative imaging studies included computed tomography (CT)-sestamibi (n = 3), CT neck (n = 4), CT chest (n = 6), and neck ultrasound (n = 6). Intraoperative PTH measurements found >50% reduction in all cases. Average length of surgery was 108.6 minutes (range: 76-186); average blood loss 26 cc. All specimens were parathyroid adenomas, with an average size of 16 mm (range: 7-35 mm). Seven of eight patients were discharged on postoperative day 1. No complications or recurrences occurred at a median follow-up of 18.5 days (range: 15-1,066 days). Conclusions: Robot-assisted thoracoscopic parathyroidectomy is a safe and effective technique, with immediate improvement in PTH levels. Thorough clinical, biochemical, and radiologic preoperative workup assists in operative planning and may improve diagnostic accuracy of anterior mediastinal masses.

Government Legislation in Response to the Opioid Epidemic.

PURPOSE OF REVIEW: Opioid misuse and abuse in the USA has evolved into an epidemic of tragic pain and suffering, resulting in the estimated death of over 64,000 people in 2016. Governmental regulation has escalated alongside growing awareness of the epidemic's severity, both on the state and federal levels. RECENT FINDINGS: This article reviews the timeline of government interventions from the late 1990s to today, including the declaration of the opioid crisis as a national public health emergency and the resultant changes in funding and policy across myriad agencies. Aspects of the cultural climate that fuel the epidemic, and foundational change that may promote sustained success against it, are detailed within as well. As a consequence of misuse and abuse of opioids, governmental regulation has attempted to safeguard society, and clinicians should appreciate changes and expectations of prescribers.

Safety Profiles of Fat Processing Techniques in Autologous Fat Transfer for Breast Reconstruction.

BACKGROUND: Autologous fat transfer is common in breast reconstruction because of its versatility for use in contour deformities. The authors examined three different fat grafting processing techniques for complications and safety profile using their institutional database. METHODS: Retrospective review was performed of patients from a single institution who had undergone autologous fat transfer following breast reconstruction from 2012 to 2016. Individuals were separated into three cohorts according to fat harvest technique: (1) centrifugation, (2) Telfa gauze, or (3) Revolve. Complications between the groups were assessed. RESULTS: A total of 267 cases of autologous fat transfer were identified (centrifugation, n = 168; Telfa, n = 44; and Revolve, n = 55). Grafting by means of centrifugation was associated with the greatest incidence of oil cysts (12.5 percent; p = 0.034), postoperative adverse events observed in the clinic (13.7 percent; p = 0.002), and total complications (25.6 percent; p = 0.001). The use of Telfa resulted in the lowest rates of oil cyst formation (0 percent; p = 0.002) and total complications (2.3 percent; p = 0.001). Grafting by means of centrifugation was also associated with the highest frequency of repeated injections among the three techniques after initial grafting (19.6 percent; p = 0.029). In contrast, Revolve demonstrated a repeated injection rate of just 5.45 percent, significantly lower when independently compared with centrifugation (p = 0.011). Multivariate analysis demonstrated that higher total graft volume (p = 0.002) and the use of centrifugation (p = 0.002) were significant risk factors for adverse events seen in the clinic postoperatively. CONCLUSIONS: Significant differences in postoperative outcomes exist between varying fat transfer techniques. Autologous fat transfer by means of centrifugation harbored the highest rates of complication, whereas Telfa and Revolve exhibited similar safety profiles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.