Toward Precision Psychiatry: Statistical Platform for the Personalized Characterization of Natural Behaviors.
ABSTRACT: There is a critical need for new analytics to personalize behavioral data analysis across different fields, including kinesiology, sports science, and behavioral neuroscience. Specifically, to better translate and integrate basic research into patient care, we need to radically transform the methods by which we describe and interpret movement data. Here, we show that hidden in the "noise," smoothed out by averaging movement kinematics data, lies a wealth of information that selectively differentiates neurological and mental disorders such as Parkinson's disease, deafferentation, autism spectrum disorders, and schizophrenia from typically developing and typically aging controls. In this report, we quantify the continuous forward-and-back pointing movements of participants from a large heterogeneous cohort comprising typical and pathological cases. We empirically estimate the statistical parameters of the probability distributions for each individual in the cohort and report the parameter ranges for each clinical group after characterization of healthy developing and aging groups. We coin this newly proposed platform for individualized behavioral analyses "precision phenotyping" to distinguish it from the type of observational-behavioral phenotyping prevalent in clinical studies or from the "one-size-fits-all" model in basic movement science. We further propose the use of this platform as a unifying statistical framework to characterize brain disorders of known etiology in relation to idiopathic neurological disorders with similar phenotypic manifestations.
Project description:Nystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular phenotyping using commonly available phenotyping methods and were grouped into four sub-cohorts according to the level of phenotyping information gained and their findings. DNA was extracted and sequenced using a broad utility next generation sequencing (NGS) gene panel. A clinical subpanel of genes for nystagmus/albinism was utilised and likely causal variants were prioritised according to methods currently employed by clinical diagnostic laboratories. We determine the likely underlying genetic cause for 43.2% of participants with similar yields regardless of prior phenotyping. This study demonstrates that a diagnostic workflow combining basic ocular phenotyping and a clinically available targeted NGS panel, can provide a high diagnostic yield for patients with infantile nystagmus, enabling access to disease specific management at a young age and reducing the need for multiple costly, often invasive tests. By describing diagnostic yield for groups of patients with incomplete phenotyping data, it also permits the subsequent design of 'real-world' diagnostic workflows and illustrates the changing role of genetic testing in modern diagnostic workflows for heterogeneous ophthalmic disorders.
Project description:The conceptual physical education (CPE) innovation began in the mid-20th century as an alternative approach to college-level, activity-only basic instruction classes. In addition to physical activity sessions, CPE courses (classes) use text material and classroom sessions to teach kinesiology concepts and principles of health-related fitness and health-enhancing physical activity. CPE courses are now offered in nearly all college programs as either required or electives classes. Two decades later, the high school CPE innovation began, and Kindergarten-8 programs followed. In this commentary, I argue that historian Roberta Park was correct in her assessment that physical education has the potential to be the renaissance field of the 21st century. Scientific contributions of researchers in kinesiology will lead the way, but science-based CPE and companion fitness education programs that align with physical education content standards and fitness education benchmarks will play a significant role. CPE courses have been shown to be effective in promoting knowledge, attitudes, and out-of-school physical activity and have the potential to elevate physical education as we chart the course of our future.
Project description:Behavior provides important insights into neuronal processes. For example, analysis of reaching movements can give a reliable indication of the degree of impairment in neurological disorders such as stroke, Parkinson disease, or Huntington disease. The analysis of such movement abnormalities is notoriously difficult and requires a trained evaluator. Here, we show that a deep neural network is able to score behavioral impairments with expert accuracy in rodent models of stroke. The same network was also trained to successfully score movements in a variety of other behavioral tasks. The neural network also uncovered novel movement alterations related to stroke, which had higher predictive power of stroke volume than the movement components defined by human experts. Moreover, when the regression network was trained only on categorical information (control = 0; stroke = 1), it generated predictions with intermediate values between 0 and 1 that matched the human expert scores of stroke severity. The network thus offers a new data-driven approach to automatically derive ratings of motor impairments. Altogether, this network can provide a reliable neurological assessment and can assist the design of behavioral indices to diagnose and monitor neurological disorders.
Project description:Static taping of the ankle or knee joint is a common method of reducing risk of injury by providing mechanical stability. An alternative taping technique employs kinesiology tape, which has the additional benefit of improving functionality by stimulating proprioception. There is substantial disagreement whether kinesiology tape shows significant differences in proprioception and postural stability as compared to rigid/static tape when applied at the lower limb. The current study investigated the effects of kinesiology tape and static tape during a Y Balance Test on center of mass as an indicator for postural stability. Forty-one individuals, free of injury, performed the Y Balance Test under the three conditions; no tape, kinesiology tape, and static tape applied at the lower limb to the quadriceps, triceps surae and ankle joint. All participants completed the Y Balance Test to determine whether any significant differences could be observed using center of mass movement as a surrogate measure for balance and proprioception. The Minkowski-Bouligand and box-counting fractal dimension analyses were used as measures of the dynamic changes in the center of mass whilst undertaking the Y Balance Test. Statistical analyses included the Kruskal Wallis test to allow for non-normally distributed data and a Bonferroni corrected pairwise T-test as a post hoc test to ascertain pairwise differences between the three taping conditions. Significance was set at 0.05. The fractal analyses of the dynamic changes in center of mass showed significant differences between the control and both the static tape and kinesiology tape groups (p = 0.021 and 0.009, respectively). The current study developed a novel measure of dynamic changes in the center of mass during a set movement that indicated real-time processing effects during a balance task associated with the type of taping used to enhance postural stability.
Project description:There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders.
Project description:<b>Background:</b> According to dynamical systems theory, an increase in movement variability leads to greater adaptability, which may be related to the number of feedforward and feedback mechanisms associated with movement and postural control. Using Higuchi dimension (HDf) to measure complexity of the signal and Singular Value Decomposition Entropy (SvdEn) to measure the number of attributes required to describe the biosignal, the purpose of this study was to determine the effect of kinesiology and strapping tape on center of pressure dynamics, myoelectric muscle activity, and joint angle during the Y balance test. <b>Method:</b> Forty-one participants between 18 and 34 years of age completed five trials of the Y balance test without tape, with strapping tape (ST), and with kinesiology tape (KT) in a cross-sectional study. The mean and standard errors were calculated for the center of pressure, joint angles, and muscle activities with no tape, ST, and KT. The results were analyzed with a repeated measures ANOVA model (<i>P</i> <sub><i>A</i></sub> < <i>0.05)</i> fit and followed by <i>Tukey post hoc</i> analysis from the R package with probability set at <i>P</i> < 0.05. <b>Results:</b> SvdEn indicated significantly decreased complexity in the anterior-posterior (<i>p</i> < 0.05) and internal-external rotation (<i>p</i> < 0.001) direction of the ankle, whilst HDf for both ST and KT identified a significant increase in ankle dynamics when compared to no tape (<i>p</i> < 0.0001) in the mediolateral direction. Taping also resulted in a significant difference in gastrocnemius muscle myoelectric muscle activity between ST and KT (<i>p</i> = 0.047). <b>Conclusion:</b> Complexity of ankle joint dynamics increased in the sagittal plane of movement with no significant changes in the possible number of physiological attributes. In contrast, the number of possible physiological attributes contributing to ankle movement was significantly lower in the frontal and transverse planes. Simply adhering tape to the skin is sufficient to influence neurological control and adaptability of movement. In addition, adaptation of ankle joint dynamics to retain postural stability during a Y Balance test is achieved differently depending on the direction of movement.
Project description:Sleep is a conserved behavior across the evolutionary timescale. Almost all known animal species demonstrate sleep or sleep like states. Despite extensive study, the mechanistic aspects of sleep need are not very well characterized. Sleep appears to be needed to generate resources that are utilized during the active stage/wakefulness as well as clearance of waste products that accumulate during wakefulness. From a metabolic perspective, this means sleep is crucial for anabolic activities. Decrease in anabolism and build-up of harmful catabolic waste products is also a hallmark of aging processes. Through this lens, sleep and aging processes are remarkably parallel- for example behavioral studies demonstrate an interaction between sleep and aging. Changes in sleep behavior affect neurocognitive phenotypes important in aging such as learning and memory, although the underlying connections are largely unknown. Here we draw inspiration from the similar metabolic effects of sleep and aging and posit that large scale metabolic phenotyping, commonly known as metabolomics, can shed light to interleaving effects of sleep, aging and progression of diseases related to aging. In this review, data from recent sleep and aging literature using metabolomics as principal molecular phenotyping methods is collated and compared. The present data suggests that metabolic effects of aging and sleep also demonstrate similarities, particularly in lipid metabolism and amino acid metabolism. Some of these changes also overlap with metabolomic data available from clinical studies of Alzheimer's disease. Together, metabolomic technologies show promise in elucidating interleaving effects of sleep, aging and progression of aging disorders at a molecular level.
Project description:Studies of eye movement have become an essential tool of basic neuroscience research. Measures of eye movement have been applied to higher brain functions such as cognition, social behavior, and higher-level decision-making. With the development of eye trackers, a growing body of research has described eye movements in relation to mental disorders, reporting that the basic oculomotor properties of patients with mental disorders differ from those of healthy controls. Using discrimination analysis, several independent research groups have used eye movements to differentiate patients with schizophrenia from a mixed population of patients and controls. Recently, in addition to traditional oculomotor measures, several new techniques have been applied to measure and analyze eye movement data. One research group investigated eye movements in relation to the risk of autism spectrum disorder several years prior to the emergence of verbal-behavioral abnormalities. Research on eye movement in humans in social communication is therefore considered important, but has not been well explored. Since eye movement patterns vary between patients with mental disorders and healthy controls, it is necessary to collect a large amount of eye movement data from various populations and age groups. The application of eye trackers in the clinical setting could contribute to the early treatment of mental disorders.
Project description:Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals.
Project description:Aging-related changes have been identified at virtually every level of the central auditory system. One of the most common findings across these nuclei is a loss of synaptic inhibition with aging, which has been proposed to be at the heart of several aging-related changes in auditory cognition, including diminished speech perception in complex environments and the presence of tinnitus. Some authors have speculated that downregulation of synaptic inhibition is a consequence of peripheral deafferentation and therefore is a homeostatic mechanism to restore excitatory/inhibitory balance. As such, disinhibition would represent a form of maladaptive plasticity. However, clinical data suggest that deafferentation-related disinhibition tends to occur primarily in the aged brain. Therefore, aging-related disinhibition may, in part, be related to the high metabolic demands of inhibitory neurons relative to their excitatory counterparts. These findings suggest that both deafferentation-related maladaptive plastic changes and aging-related metabolic factors combine to produce changes in central auditory function. Here, we explore the arguments that downregulation of inhibition may be due to homeostatic responses to diminished afferent input vs. metabolic vulnerability of inhibitory neurons in the aged brain. Understanding the relative importance of these mechanisms will be critical for the development of treatments for the underlying causes of aging-related central disinhibition.