A novel CNN-based image segmentation pipeline for individualized feline spinal cord stimulation modeling.

Objective. Spinal cord stimulation (SCS) is a well-established treatment for managing certain chronic pain conditions. More recently, it has also garnered attention as a means of modulating neural activity to restore lost autonomic or sensory-motor function. Personalized modeling and treatment planning are critical aspects of safe and effective SCS (Rowald and Amft 2022 Front. Neurorobotics 16 983072, Wagneret al2018 Nature 563 65-71). However, the generation of spine models at the required level of detail and accuracy requires time and labor intensive manual image segmentation by human experts. This study aims to develop a maximally automated segmentation routine capable of producing high-quality anatomical models, even with limited data, to facilitate safe and effective personalized SCS treatment planning.Approach. We developed an automated image segmentation and model generation pipeline based on a novel convolutional neural network (CNN) architecture trained on feline spinal cord magnetic resonance imaging data. The pipeline includes steps for image preprocessing, data augmentation, transfer learning, and cleanup. To assess the relative importance of each step in the pipeline and our choice of CNN architecture, we systematically dropped steps or substituted architectures, quantifying the downstream effects in terms of tissue segmentation quality (Jaccard index and Hausdorff distance) and predicted nerve recruitment (estimated axonal depolarization).Main results. The leave-one-out analysis demonstrated that each pipeline step contributed a small but measurable increment to mean segmentation quality. Surprisingly, minor differences in segmentation accuracy translated to significant deviations (ranging between 4% and 13% for each pipeline step) in predicted nerve recruitment, highlighting the importance of careful workflow design. Additionally, transfer learning techniques enhanced segmentation metric consistency and allowed generalization to a completely different spine region with minimal additional training data.Significance. To our knowledge, this work is the first to assess the downstream impacts of segmentation quality differences on neurostimulation predictions. It highlights the role of each step in the pipeline and paves the way towards fully automated, personalized SCS treatment planning in clinical settings.

A Computational Study of Lower Urinary Tract Nerve Recruitment with Epidural Stimulation of the Lumbosacral Spinal Cord.

Bladder dysfunction is a major health risk for people with spinal cord injury. Recently, we have demonstrated that epidural sacral spinal cord stimulation (SCS) can be used to activate lower urinary tract nerves and provide both major components of bladder control: voiding and continence. To effectively control these functions, it is necessary to selectively recruit the afferents of the pudendal nerve that evoke these distinct bladder reflexes. Translation of this innovation to clinical practice requires an understanding of optimal electrode placements and stimulation parameters to guide surgical practice and therapy design. Computational modeling is an important tool to address many of these experimentally intractable stimulation optimization questions. Here, we built a realistic MRI-based finite element computational model of the feline sacral spinal cord which included realistic axon trajectories in the dorsal and ventral roots. We coupled the model with biophysical simulations of membrane dynamics of afferent and efferent axons that project to the lower urinary tract through the pelvic and pudendal nerves. We simulated the electromagnetic fields arising from stimulation through SCS electrodes and calculated the expected recruitment of pelvic and pudendal fibers. We found that SCS can selectively recruit pudendal afferents, in agreement with our experimental data in cats. Our results suggest that SCS is a promising technology to improve bladder function after spinal cord injury, and computational modeling unlocks the potential for highly optimized, selective stimulation. Clinical Relevance - This model provides a method to non-invasively establish electrode placement and stimulation parameters for improving bladder function with epidural spinal cord stimulation.

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis.

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

In silico voltage-sensitive dye imaging reveals the emergent dynamics of cortical populations.

Voltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Using this model, we extend previous experimental observations regarding the cellular origins of VSDI, finding that the signal is driven primarily by neurons in layers 2/3 and 5, and that VSDI measurements do not capture individual spikes. Furthermore, we test the capacity of VSD image sequences to discriminate between afferent thalamic inputs at various spatial locations to estimate a lower bound on the functional resolution of VSDI. Our approach underscores the power of a bottom-up computational approach for relating scales of cortical processing.

Stabilization of cultural innovations depends on population density: Testing an epidemiological model of cultural evolution against a global dataset of rock art sites and climate-based estimates of ancient population densities.

Demographic models of human cultural evolution have high explanatory potential but weak empirical support. Here we use a global dataset of rock art sites and climate and genetics-based estimates of ancient population densities to test a new model based on epidemiological principles. The model focuses on the process whereby a cultural innovation becomes endemic in a population, predicting that this cannot occur unless population density exceeds a critical threshold. Analysis of the data, using a Bayesian statistical framework, shows that the model has stronger empirical support than a proportional model, where detection is directly proportional to population density, or a null model, where rock art detection ratios and population density are independent. Results for different geographical areas and periods are compatible with the predictions of the model and confirm its superiority with respect to the null model. Re-analysis of the rock art data, using a second set of independent population estimates, again supports the superiority of the model. Although the available data is sparse and the analysis cannot exclude all possible sources of bias, this is evidence that population density above a critical threshold may be a necessary condition for the maintenance of rock art as a stable part of a population's cultural repertoire. Methods similar to those described can be used to test the model for other classes of archaeological artifact and to compare it against other models.

Undulatory Locomotion of Magnetic Multilink Nanoswimmers.

Micro- and nanorobots operating in low Reynolds number fluid environments require specialized swimming strategies for efficient locomotion. Prior research has focused on designs mimicking the rotary corkscrew motion of bacterial flagella or the planar beating motion of eukaryotic flagella. These biologically inspired designs are typically of uniform construction along their flagellar axis. This work demonstrates for the first time planar undulations of composite multilink nanowire-based chains (diameter 200 nm) induced by a planar-oscillating magnetic field. Those chains comprise an elastic eukaryote-like polypyrrole tail and rigid magnetic nickel links connected by flexible polymer bilayer hinges. The multilink design exhibits a high swimming efficiency. Furthermore, the manufacturing process enables tuning the geometrical and material properties to specific applications.

Language-based access to gestural components of conceptual knowledge.

We report two experiments in which production of articulated hand gestures was used to reveal the nature of gestural knowledge evoked by sentences referring to manipulable objects. Two gesture types were examined: functional gestures (executed when using an object for its intended purpose) and volumetric gestures (used when picking up an object simply to move it). Participants read aloud a sentence that referred to an object but did not mention any form of manual interaction (e.g., Jane forgot the calculator) and were cued after a delay of 300 or 750 ms to produce the functional or volumetric gesture associated with the object, or a gesture that was unrelated to the object. At both cue delays, functional gestures were primed relative to unrelated gestures, but no significant priming was found for volumetric gestures. Our findings elucidate the types of motor representations that are directly linked to the meaning of words referring to manipulable objects in sentences.

Prevalence and associated factors of hepatitis C infection (HCV) in a multi-site Canadian population of illicit opioid and other drug users (OPICAN).

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent in illicit drug user populations, with three in four new HCV infections related to this risk behaviour and a growing HCV disease burden in Canada. Using data from a multi-site cohort study of illicit opioid users in five Canadian cities (OPICAN), this paper explores the prevalence and predictors of HCV status in this high-risk population. METHODS: HCV status of cohort participants was assessed by salivary antibody test. Univariate relationships of HCV status with select variables were examined on the basis of cohort baseline data, and subsequently multivariate models using logistic regression to determine independent predictors of HCV status were generated. RESULTS: 54.6% of the analysis sample (n=482) was HCV positive. Significant differences in terms of HCV prevalence existed across the sites. Significant variables in the final stepwise logistic regression model included age, site (Toronto), unprotected sex, injecting drug use, drug treatment and incarceration in past year, in addition to opioid use in combination with non-opioids. DISCUSSION: Besides drug injecting, various other socio-behavioural factors were associated with HCV status in our cohort. On this basis, interventions focusing solely on injection risks are overly limited in scope to prevent HCV transmission in the high-risk population of illicit drug users and need to be broadened. Prevention efforts should also target young injectors as a priority.

Illicit drug use among Canadian University undergraduates.

The purpose of this study was to examine rates and patterns of illicit drug use among Canadian university undergraduates, to compare these rates with those for non-university samples, and to describe drug-use trends among university undergaduates in the province of Ontario between 1988 and 1998. A national mail survey was carried out based on stratified 2-stage sample design. The sample comprised 7,800 Canadian undergraduates from 16 universities (52% of eligible respondents). Approximately 47.5% reported use of illicit drug durning their life, 29.6% in the previous 12 months, and 18.7% since the beginning of the academic year. Cannabis was by far the most widley used drug (47.0%, 28.7%, and18.2%, respectively). Many of the gender and regional associations were similar to those found in general-populations surveys. Comparisons to non-university peers did not indicate elevated rates among university students. Among Ontario university undergraduates the use of cannabis, hallucinogens, methamphetamines, crack, and herion remained stable between 1988 and 1998. The use of cocaine declined from 4.8% to 1.7%. Rates of illicit drug use were not appreciably higher than those among their non-university peers. Other public-health issues, such as heavy drinking and poor mental health, override those related to illicit drug use.

Heavy drinking on Canadian campuses.

OBJECTIVE: To describe the prevalence and frequency of heavy drinking episodes among Canadian undergraduates. METHODS: Data are drawn from the Canadian Campus Survey, a national mail survey, conducted in the fall of 1998, with a random sample of 7,800 students from 16 universities. RESULTS: Overall, 62.7% and 34.8% of students reported consuming 5 or more drinks and 8 or more drinks, respectively, on a single occasion at least once during the fall semester. On average, drinkers reported having 5 or more drinks almost 5 times during the fall semester, and having 8 or more drinks almost twice during the same period. The groups reporting the highest rates of heavy drinking were males, those living in university residences, those with low academic orientation and those with high recreational orientation. INTERPRETATION: Generally, this study has shown that heavy drinking is highly engrained in Canadian undergraduates' drinking patterns, and is related to a number of factors. These factors can be used to develop targeted prevention efforts.

Cigarette use among Canadian undergraduates.

OBJECTIVE: To describe the prevalence of daily cigarette use among Canadian undergraduates. Estimates are also compared to earlier Ontario surveys. METHODS: Data are drawn from the Canadian Campus Survey, a national mail survey, conducted in the fall of 1998, with a random sample of 7,800 students from 16 universities. RESULTS: Overall, 17.1% reported daily cigarette smoking and 10.4% reported occasional smoking. Rates of daily smoking differed significantly by region (with rates above average among those attending university in the Atlantic and below average among those attending university in British Columbia and the Prairies), residence (those residing off campus without family reported the highest prevalence rate), and year of study (those in the final year typically reported lower rate of use). INTERPRETATION: University campuses represent an environment with potential gains to be made by tobacco control policies.

Drug treatment courts--a viable option for Canada? Sentencing issues and preliminary findings from the Toronto court.

The first drug treatment court in Canada began operation in Toronto in December of 1998. This paper describes some aspects of the evolution, structure, and operation of this court. In addition, the federally-funded evaluation of the new program has produced data from the first 18 months of its full operation when 198 drug-dependent individuals were admitted. These preliminary results are described and compared to the findings of an Australian study and to select American studies. Important differences in sentencing practices and options for drug offenses between Canada and the United States are highlighted. Even at this early stage of development, it is suggested that the types of clients retained and more successful in this Canadian experiment may be quite different from the more typical American drug treatment court clientele. The need for careful monitoring and more complete, long-term information is emphasized before the viability of this approach is established for Canada.

Multilevel analysis of situational drinking among Canadian undergraduates.

Using a multi-level approach, we examined the contribution of drinking setting characteristics and of individual characteristics on the alcohol intake per drinking occasion. The data are drawn from the Canadian Campus Survey, a national mail survey conducted in 1998 with a random sample of 8,864 students in 18 universities. For each student, up to five drinking occasions were investigated, resulting in 26,348 drinking occasions among 6,850 drinkers. At the individual level this study focused on the university life experience. At the situational level, information about alcohol intake was recorded relative to why, when, where and with whom drinking occurred. Our results show that drinking setting is as important as the individual characteristics in explaining the alcohol intake per occasion. Policies aimed at reducing students alcohol intake may be more beneficial if they address both situational and individual factors.

The prevalence of elevated psychological distress among Canadian undergraduates: findings from the 1998 Canadian Campus Survey.

For a study of elevated psychological distress, the authors used data based on a national probability sample of 7,800 Canadian undergraduate students from 16 universities. They used the 12-item General Health Questionnaire to assess mental health. Thirty percent of the students in the sample reported elevated psychological distress, which varied significantly according to sex, region, year of study, and recreational and academic orientation. Rates of elevated distress were significantly higher among the students than among the general population in Canada.

Measuring treatment process beliefs among staff of specialized addiction treatment services.

In a survey conducted in Ontario, front-line staff of specialized addiction treatment services were asked to indicate the extent to which they believed 53 different treatment processes to be necessary for the effective treatment of people with alcohol and drug problems. Cognitive-behavioural processes were generally rated as almost essential for treatment to be effective. Other processes received mixed ratings, while confrontation and pharmacological treatment were, on average, rated as detrimental. Factor analysis identified three interpretable dimensions of beliefs (a) cognitive-behavioural, (b) disease, and (c) medication. A fourth dimension involved both psychodynamic and conditioning processes and did not clearly correspond with any known therapeutic approach. Scores on scales developed using items from these four dimensions were variously influenced by respondents age, education, place of work, and certification status. Two groups identified using cluster analysis differed primarily with respect to scores on the disease scale. Logistic regression analysis showed that age, certification status, and place of work were associated with membership in these groups. Implications for treatment system development and research are discussed.

Prevalence and factors associated with physical and sexual assault of female university students in Ontario.

The authors examined the prevalence of physical and sexual assault of female university students and associated factors. In a survey of a random sample of 3,642 female students from 6 universities across Ontario, 24% of female students reported being physically assaulted and 15% reported being sexually assaulted during the previous year. When the assault measures were combined, 32% of university women reported being either physically or sexually assaulted during the previous year. Of those experiencing assault, 40% had been the victim of 2 or more types of assaults. Logistic regression analysis revealed that assault was associated with year of study, marital status, alcohol consumption, illicit drug use, prescription drug use, unhealthy eating and stress behaviors, less time spent on academics, and more time involved in social activities. University programs and activities directed toward the reduction of assault should incorporate the factors identified in this study to increase awareness of the situational factors surrounding likelihood of assault.

Perceived coercion among clients entering substance abuse treatment: structural and psychological determinants.

Little is known about the extent to which admission to alcohol and other drug treatment programs is perceived as a coercive imposition. This is because coercion is typically inferred from referral source rather than measured. In this study, clients (N = 300) entering substance abuse treatment were assessed on structural variables (sociodemographic background, criminal history, current legal status, referral source), psychological variables (personal beliefs about substance abuse, perceived interpersonal pressures), alcohol/drug use, and perceived coercion. Mandated treatment status predicted perceived coercion; however, many mandated clients did not, and many self-referrals did, report being coerced into treatment. Psychological factors accounted for additional variance in perceived coercion, controlling for referral source. Substance dependence did not add to the predictability of perceived coercion beyond structural and psychological variables. These findings are inconsistent with the notion that coercion can be inferred from referral source. Instead, results support self-determination theory (Deci & Ryan, 1985), which proposes that multiple social and psychological events promote perceived coercion by undermining personal autonomy.

Toward comprehensive school drug policy in Ontario.

The study reported here examines the development and implementation of School Drug Policy in Ontario Boards of Education, the components of these policies, and the composition of policy development committees. Data from 125 Boards of Education were obtained from responses to a questionnaire administered in the Fall of 1991. Findings from the study indicate that school drug policies are increasingly comprehensive-including not only disciplinary measures, but also a preventive curriculum and early intervention component. The composition of policy development working groups normally consisted of such groups as board personnel, teachers, and practitioners from other fields. Students were not often included in the process of policy development. Thus, the development and implementation of school drug policy in Ontario indicates a "top down" rather than "bottom up" approach.

Characteristics of drug users admitted to alcohol detoxication centers.

A survey of admissions to Ontario's alcohol detoxication centers showed many admissions used alcohol in combination with other drugs, and a poor correspondence between self-reports and results of the urine analysis. The use of THC was more common among younger admissions with low urine alcohol levels. Benzodiazepine use was more common among referrals from hospitals, general practitioners, and those presenting with cuts and bruises.

Long-term trends in male drunkenness arrests in metropolitan Toronto: effects of social-setting detoxication centers.

Drunkenness arrest rates for adult males in Toronto decreased substantially during the period 1966 to 1987. In 1971 there was a change in legislation permitting police to take public inebriates to detoxication centers. Drunkenness rates continued to decline at a rate similar to that for the previous 3 years. The next year drunkenness arrests increased but subsequently declined at a rate which was 50% greater than that which preceded the change in legislation. Since 1973 year by year changes in the rate of male drunkenness arrests have not been consistently related to rates of police admission to detoxication centers or to total admissions to detoxication centers. The results suggest that recent trends in drunkenness arrests have been influenced by the 1971 change in legislation and the increased use of detoxication centers. However, the influence of other factors must also be considered.