Subtle Behavioral Changes Research Articles

The possible impact of vulnerability on clinical communication: Some reflections and a call for empirical studies

ObjectiveTo direct attention to the concept of vulnerability, how it affects interactions in subtle ways and is difficult to detect in studies of clinical dialogues. MethodsA reflection on three everyday examples of what seems like insignificant details in physician-patient interaction, enlightened by readings with an emphasis on unacknowledged shame, illness and social bonds, and the physician’s role. ResultsPhysicians are aware of patients’ vulnerability as risk and susceptibility to harm under certain circumstances, but often miss the vulnerability related to perceived or anticipated loss of social bonds. The latter may elicit unacknowledged shame, which leads to subtle behavioral changes that are easy to overlook. Typical reactions are silence or lack of relevant response to questions. Physicians are rarely aware of their own vulnerability. Slight behavioral changes from a clinician may reduce or increase a patient’s ability to partake actively in problem solving and decision-making. ConclusionWhen physicians or patients are touching upon unacknowledged shame as part of being vulnerable, subtle changes in the interaction may hamper efficient communication. Practice implicationsWe need studies that add participants’ unprompted and prompted reflections on encounter videos, with an emphasis on micro-events and their explanation and impact on the interaction.

Forebrain Control of Behaviorally Driven Social Orienting in Zebrafish

Deficits in social engagement are diagnostic of multiple neurodevelopmental disorders, including autism and schizophrenia [1]. Genetically tractable animal models like zebrafish (Danio rerio) could provide valuable insight into developmental factors underlying these social impairments, but this approach is predicated on the ability to accurately and reliably quantify subtle behavioral changes. Similarly, characterizing local molecular and morphological phenotypes requires knowledge of the neuroanatomical correlates of social behavior. We leveraged behavioral and genetic tools in zebrafish to both refine our understanding of social behavior and identify brain regions important for driving it. We characterized visual social interactions between pairs of adult zebrafish and discovered that they perform a stereotyped orienting behavior that reflects social attention [2]. Furthermore, in pairs of fish, the orienting behavior of one individual is the primary factor driving the same behavior in the other individual. We used manual and genetic lesions to investigate the forebrain contribution to this behavior and identified a population of neurons in the ventral telencephalon whose ablation suppresses social interactions, while sparing other locomotor and visual behaviors. These neurons are cholinergic and express the gene encoding the transcription factor Lhx8a, which is required for development of cholinergic neurons in the mouse forebrain [3]. The neuronal population identified in zebrafish lies in a region homologous to mammalian forebrain regions implicated in social behavior such as the lateral septum [4]. Our data suggest that an evolutionarily conserved population of neurons controls social orienting in zebrafish.

Mapping Movement: Applying Motion Measurement Technologies to the Psychiatric Care of Older Adults.

Recent advances in technology have changed the landscape of treatment for adults with mental illness. This review highlights technological innovations that may improve care for older adults with mental illness and neurocognitive disorders through the measurement and assessment of physical motion. These technologies include wearable sensors (such as smart watches and Fitbits), passive motion sensors, and smart home models that incorporate both active and passive motion technologies. Clinicians have evaluated motion measurement technologies in older adults with depression, dementia, anxiety, and schizophrenia. Results from studies in dementia populations suggest that motion measurement technologies can assist clinicians in diagnosing dementia earlier through the evaluation of gait, balance, and postural kinematics. Motion detection technologies can also be used to identify mood episodes at an earlier stage by detecting subtle behavioral changes. Clinicians may use the objective data provided by technologies such as accelerometers to identify illnesses earlier, which may inform treatment decisions. The data may be used as a suitable surrogate marker for detecting depression in older adults, predicting the likelihood of falls, or quantifying physical activity in older adults with chronic mental illnesses or anxiety. Motion-based technologies also have the potential to detect physical activity for older adults residing in nursing homes. Wearable technologies are generally well tolerated in older adults, although the use of new technology and electronic health data could involve privacy and security concerns among this vulnerable population.

Constitutive plasma membrane monoamine transporter (PMAT, Slc29a4) deficiency subtly affects anxiety-like and coping behaviours.

Originally, uptake-mediated termination of monoamine (e.g., serotonin and dopamine) signalling was believed to only occur via high-affinity, low-capacity transporters ("uptake1 ") such as the serotonin or dopamine transporters, respectively. Now, the important contribution of a second low-affinity, high-capacity class of biogenic amine transporters has been recognised, particularly in circumstances when uptake1 transporter function is reduced (e.g., antidepressant treatment). Pharmacologic or genetic reductions in uptake1 function can change locomotor, anxiety-like or stress-coping behaviours. Comparable behavioural investigations into reduced low-affinity, high-capacity transporter function are lacking, in part, due to a current dearth of drugs that selectively target particular low-affinity, high-capacity transporters, such as the plasma membrane monoamine transporter. Therefore, the most direct approach involves constitutive genetic knockout of these transporters. Other groups have reported that knockout of the low-affinity, high-capacity organic cation transporters 2 or 3 alters anxiety-like and stress-coping behaviours, but none have assessed behaviours in plasma membrane monoamine transporter knockout mice. Here, we evaluated adult male and female plasma membrane monoamine transporter wild-type, heterozygous and knockout mice in locomotor, anxiety-like and stress-coping behavioural tests. A mild enhancement of anxiety-related behaviour was noted in heterozygous mice. Active-coping behaviour was modestly and selectively increased in female knockout mice. These subtle behavioural changes support a supplemental role of plasma membrane monoamine transporter in serotonin and dopamine uptake, and suggest sex differences in transporter function should be examined more closely in future investigations.

Influence of the use of cane on the gait cycle of individuals who are blind

The aim of this study was to perform a biomechanical characterization of the gait cycle in individuals who are blind. Five individuals with ages between 16 and 19 years participated in this study. The task consisted of walks of 12m measured in two conditions: (1) with cane and (2) wihtout cane; a total of 20 walks in each condition were performed. During walks, participants were monitored with a Vicon 3D-motion capture system. Spatialtemporal, kinematic, kinetic, and dynamic parameters were recorded and compared between the two conditions. We observed an interaction between the condition and ankle angular measures ( p = .003); the interaction was due to differences induced by condition in instants ‘opposite toe off’ ( p = .045) and ‘opposite initial contact’ ( p = .019). We also obtained a significant difference in the negative ankle-joint-power measures between conditions ( p = .044). This study showed that the use of cane changes the gait pattern in individuals who are blind. The subtle changes in ankle behaviour when walking with a cane, compared with no cane, suggest better application of the force during the initial stages of support leading to a more comfortable gait. This type of assessment of gait may be important to improve mobility training and rehabilitation strategies.

Collagen morphology influences macrophage shape and marker expression in vitro

Fibrosis is a process in which an accumulation of extracellular matrix (ECM) leads to an impaired function of the affected organ. Pulmonary fibrosis is the end-stage of several lung diseases, characterized by scarring of the lungs. Although macrophages are known to be important players in ECM homeostasis, their ability to respond to fibrosis-related morphological and mechanical changes of the ECM is relatively unexplored. In this study we aimed to elucidate the effect of ECM stiffness and morphology on macrophage polarization, by using a collagen type I-based in vitro system. Collagen morphology, but not stiffness, affected the relative expression of CD206 (the mannose receptor) and Ym1 (a murine marker of pro-healing M2 macrophages). Higher expression of Ym1 was found when macrophages were cultured on fibrous collagen. Globular collagen led to higher expression of CD206, a marker known to be upregulated on alveolar macrophages in idiopathic pulmonary fibrosis. Moreover, macrophages exhibited distinct differences in shape with actin-rich protrusions on fibrous collagen and more filopodia on globular collagen. In addition to these cytoskeletal changes, transmigration was higher when macrophages were cultured on fibrous collagen. Together these findings indicate that macrophages are sensitive to collagen morphology, responding with subtle changes in marker expression, shape and behavior rather than a complete polarization switch. This study emphasizes the complex interaction between macrophages and their surroundings, and the need for further exploration of both mechanical and morphological aspects.

Behavior and productivity of cows milked in automated systems before diagnosis of health disorders in early lactation

Associations of electronically recorded data were examined before diagnosis of health disorders in early-lactation cows in herds with automated milking systems (AMS). Rumination time, activity, and milk yield data were collected for 8 mo for 605 early-lactation cows in 9 commercial AMS herds. Using multivariable generalized linear regression models controlling for parity and days in milk, data were examined relative to the day of diagnosis for health disorders occurring in absence of, or at least 14 d before, another disorder: mastitis (n = 13), new cases of lameness (n = 45), subclinical ketosis (SCK; n = 113), and purulent vaginal discharge (n = 49). All cases of displaced abomasum (DA; n = 8) occurred in conjunction with other disorders. Deviations from baseline among affected cows were examined, as well as differences compared with a group of healthy cows and an average group of all cows, who were given mock diagnosis days using the mean days in milk at diagnosis for each disorder. On 6 to 14 d of the 2 wk before diagnosis, cows with DA or mastitis had lower milk yield, rumination time, milking frequency, activity, and milk temperature compared with healthy cows as well as deviations from their own baseline rumination time and milk data starting 4 to 12 d before diagnosis. Cows with DA had lower AMS supplement intake than healthy cows and deviations from their baseline activity and milk temperature starting 6 and 4 d before diagnosis, respectively. Cows with mastitis had greater milk conductivity than healthy cows and deviated from their baseline milking frequency and conductivity 8 and 12 d before diagnosis, respectively. Compared with healthy cows, those with SCK or new cases of lameness generally had lower milk yield, rumination time, milk temperature, supplement intake, and milking and refusal frequencies. Only the milk temperature of lame cows deviated from baseline. Thus, acute health disorders (i.e., DA and mastitis) were associated with deviations from those cows' baseline AMS data, whereas more chronic disorders (i.e., SCK and lameness) were associated with significant but subtle longer term changes in milk production and behavior. Because cows with health disorders deviated from a group of healthy cows before they deviated from their own baseline and from the average of all other cows, including a healthy reference group in health alerts could refine the ability of detection models to identify subtle deviations in early lactation.

Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APPNL−G−F mice before prominent plaque deposition

Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer’s disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APPNL−G−F knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APPNL−G−F mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APPNL mice (APP Swedish) at 3, 7 and 10 months. Mice were subjected to a test battery that referred to clinical AD symptoms, comprising cage activity, open field, elevated plus maze, social preference and novelty test, and spatial learning, reversal learning and spatial reference memory performance. Our assessment confirmed that behavior at these early ages was largely unaffected in these mice in accordance with previous reports, with some subtle behavioral changes, mainly in social and anxiety-related test performance. Resting-state functional MRI (rsfMRI) assessed connectivity between hippocampal and prefrontal regions with an established role in flexibility, learning and memory. Increased prefrontal-hippocampal network synchronicity was found in 3-month-old APPNL−G−F mice. These functional changes occurred before prominent amyloid plaque deposition.

General Practitioners’ Knowledge of a Local First-Episode Psychosis Treatment Program

General Practitioners’ Knowledge of a Local First-Episode Psychosis Treatment Program

Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.

Early detection may be the key to developing therapies that will combat Alzheimer’s disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40–60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects’ medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.

In Space and Time: Territorial Animals are Attracted to Conspecific Chemical Cues.

Territorial animals lay scent marks around their territories to broadcast their presence, but these olfactory signals can both attract and repel con-specifics. Attraction or aversion can have a profound impact in terms of space use and thereby influence an individual's access to resources and mates. Here, we test the impact of chemical signals on the long-term space use and activity of receivers, comparing the response of males and females, territory holders, and temporary visitors in Sceloporus undulatus lizards in the field. We placed either male femoral gland secretions (chemical) or blank (control) cues on resident male landmarks, repeatedly over 5 d, while monitoring the activity and location of all lizards in the vicinity. We found that resident males and females, but not non-resident males, were active on more days near landmarks treated with chemical cues than landmarks treated with control cues. Non-resident males remained closer to chemical than control cues. These results suggest that territorial scent marks are attractive to conspecifics and impact space use, but that the specific effects depend on receiver sex and residency status. Such subtle or gradual changes in behavior may frequently be overlooked by short-term choice experiments. Future studies investigating the behavioral significance of a communicative signal should consider these finer details of behavior for a more comprehensive assessment.

Trophic transfer of microplastics does not affect fish personality

Microplastics are ubiquitous in the marine environment. Their small size makes them bioavailable to a range of organisms and studies have reported ingestion across the food chain. Few studies have demonstrated physical transfer of microplastics between organisms, and no research has assessed the ecological impacts of transferred microplastics and contaminants over different trophic levels. Contaminants associated with plastics can alter animal behaviour; thus, exploring changes in behaviour may be fundamental in understanding ecosystem effects of microplastics. This study explored the effects of microplastics and associated contaminants through the food chain in the marine intertidal zone. We exposed beach hoppers, Platorchestia smithi, to environmentally relevant concentrations of microplastics and then fed them to Krefft's frillgobies, Bathygobius krefftii, ray-finned fish that inhabit shallow coastal ecosystems. We tested fish personality to see whether there were any changes that could be attributed to trophic transfer of microplastics, as even subtle changes in behaviour can have cascading effects on other organisms and the wider ecosystem. Exploring behavioural changes in response to contaminant exposure is a developing area in ecotoxicology due to its increased sensitivity compared with the traditional LD50 approach. While gobies readily ingested contaminated beach hoppers, we detected no effect of microplastic trophic transfer on fish personality relative to control groups. While chronic exposure studies assessing a suite of behaviours are required, it is possible that the transfer of microplastics via trophic interactions does not provide an additional exposure pathway for contaminants through the food web.

European sea bass show behavioural resilience to near-future ocean acidification.

Ocean acidification (OA)—caused by rising concentrations of carbon dioxide (CO2)—is thought to be a major threat to marine ecosystems and has been shown to induce behavioural alterations in fish. Here we show behavioural resilience to near-future OA in a commercially important and migratory marine finfish, the Sea bass (Dicentrarchus labrax). Sea bass were raised from eggs at 19°C in ambient or near-future OA (1000 µatm pCO2) conditions and n = 270 fish were observed 59–68 days post-hatch using automated tracking from video. Fish reared under ambient conditions, OA conditions, and fish reared in ambient conditions but tested in OA water showed statistically similar movement patterns, and reacted to their environment and interacted with each other in comparable ways. Thus our findings indicate behavioural resilience to near-future OA in juvenile sea bass. Moreover, simulated agent-based models indicate that our analysis methods are sensitive to subtle changes in fish behaviour. It is now important to determine whether the absences of any differences persist under more ecologically relevant circumstances and in contexts which have a more direct bearing on individual fitness.

Pain Treatments for Nursing Home Residents with Advanced Dementia and Substantial Impaired Communication: A Cross-Sectional Analysis at Baseline of a Cluster Randomized Controlled Trial.

This is a cross-sectional analysis at baseline of a cluster randomized controlled trial to identify factors associated with the use of pharmacological and nonpharmacological pain treatments by nursing home residents with dementia and impaired communication. One hundred thirty-four residents with dementia and impaired communication were recruited. Nine of them were excluded because data on their pain treatments were missing, resulting in 125 for analysis. Hierarchical generalized estimating equations analyses controlling for the clustering effect of nursing homes were used to identify factors associated with the use of pharmacological and nonpharmacological pain treatments. Although all participants had a confirmed pain condition, only 23 (18.4%) and 45 (36%) had received pharmacological or nonpharmacological pain treatments, respectively. Participants with a higher ability to communicate ( P = 0.031) and fewer pain locations were found to be more likely to receive pain medications, with the impact of communication ability being greater among participants with better cognitive status than among those with poor cognitive status. Participants who had been living in the home longer and who were more dependent were less likely to receive nonpharmacological treatments. Suboptimal pain management was common among this population. Severe impairment in the ability to communicate is a major reason for the underuse of pain medications. Staff may become desensitized and fail to perceive subtle changes in the residents' behavior as indicative of pain, leading to the underadministering of nonpharmacological treatments. To improve this situation, it is suggested that observational pain assessments be systematically carried out in nursing homes.

PATTERNS OF HOME COMPUTER USE DIFFER OVER TIME BETWEEN OLDER ADULTS DESTINED TO DEVELOP MILD COGNITIVE IMPAIRMENT AND THOSE WHO REMAIN COGNITIVELY INTACT

Identification of pre-symptomatic changes in healthy older adults that signal future cognitive decline and transition to MCI and AD is an important goal for early detection and intervention. Subtle changes in behavior associated with less efficient or effective performance in routine daily activities may signal incidental MCI. These changes have been correlated with cognitive tests and medial temporal lobe brain structures often affected in early AD. In this study, we examined whether patterns of responding to an in-home weekly online health questionnaire differed between older adults who remained cognitively intact and those who were destined to transition to MCI over a study period of four years. Participants were 110 community dwelling older adults enrolled in a longitudinal study of in-home monitoring technologies. At baseline in 2011, all participants were non-depressed (GDS<5) and cognitively intact (mean age = 84.8 years; 77% female). Of these individuals, 29 (26%) were classified as MCI based on neuropsychological criteria (mean age=86.0; 79% female) at an annual clinical follow-up visit (mean follow-up = 2.1 years). During the study period, a short online health questionnaire was distributed weekly through the Internet on Monday mornings at 5 am on participants’ home computers. Longitudinal generalized linear mixed effects models were generated with three online questionnaire response variables: completion time, in seconds; start time in the day, in seconds from 5am; and whether staff assistance was needed (yes/no), as unique outcomes. Models were adjusted for age, education and number of items endorsed. On average, individuals destined to develop MCI completed their questionnaires 1.4 hours later in the day than cognitively stable participants (p=.029), after adjusting for covariates. Over time, more participants needed assistance to complete the online questionnaires and this increase was significantly steeper in those destined to convert to MCI (p=0.032). The longitudinal trajectories of ambiently assessed measures of weekly home computer use differed between those who remained cognitively stable and those who were destined to transition to MCI. Remote, high frequency assessment of routine activities is a promising approach for detecting the earliest changes associated with future cognitive decline in older adults.

Early Signs of Pathological Cognitive Aging in Mice Lacking High-Affinity Nicotinic Receptors.

In order to address pathological cognitive decline effectively, it is critical to adopt early preventive measures in individuals considered at risk. It is therefore essential to develop approaches that identify such individuals before the onset of irreversible dementia. A deficient cholinergic system has been consistently implicated as one of the main factors associated with a heightened vulnerability to the aging process. In the present study we used mice lacking high affinity nicotinic receptors (β2-/-), which have been proposed as an animal model of accelerated/premature cognitive aging. Our aim was to identify behavioral signs that could serve as indicators or predictors of impending cognitive decline. We used test batteries in order to assess cognitive functions and additional tasks to investigate spontaneous behaviors, such as species-specific activities and exploration/locomotion in a novel environment. Our data confirm the hypothesis that β2-/- animals exhibit age-related cognitive impairments in spatial learning. In addition, they document age-related deficits in other areas, such as recognition memory, burrowing and nesting building, thereby extending the validity of this animal model for the study of pathological aging. Finally, our data reveal deficits in spontaneous behavior and habituation processes that precede the onset of cognitive decline and could therefore be useful as a non-invasive behavioral screen for identifying animals at risk. To our knowledge, this is the first study to perform an extensive behavioral assessment of an animal model of premature cognitive aging, and our results suggest that β2-nAChR dependent cognitive deterioration progressively evolves from initial subtle behavioral changes to global dementia due to the combined effect of the neuropathology and aging.

Advanced Behavioral Analyses Show that the Presence of Food Causes Subtle Changes in C. elegans Movement.

As a widely used and studied model organism, Caenorhabditis elegans worms offer the ability to investigate implications of behavioral change. Although, investigation of C. elegans behavioral traits has been shown, analysis is often narrowed down to measurements based off a single point, and thus cannot pick up on subtle behavioral and morphological changes. In the present study videos were captured of four different C. elegans strains grown in liquid cultures and transferred to NGM-agar plates with an E. coli lawn or with no lawn. Using an advanced software, WormLab, the full skeleton and outline of worms were tracked to determine whether the presence of food affects behavioral traits. In all seven investigated parameters, statistically significant differences were found in worm behavior between those moving on NGM-agar plates with an E. coli lawn and NGM-agar plates with no lawn. Furthermore, multiple test groups showed differences in interaction between variables as the parameters that significantly correlated statistically with speed of locomotion varied. In the present study, we demonstrate the validity of a model to analyze C. elegans behavior beyond simple speed of locomotion. The need to account for a nested design while performing statistical analyses in similar studies is also demonstrated. With extended analyses, C. elegans behavioral change can be investigated with greater sensitivity, which could have wide utility in fields such as, but not limited to, toxicology, drug discovery, and RNAi screening.

Signs of deterioration in infants discharged home following congenital heart surgery in the first year of life: a qualitative study

AimsTo describe the ways in which parents recognise and make decisions about their child's symptoms following discharge home after congenital heart interventions in the first year of life and their...

Importance of Subtle Behavioural Changes in the Diagnosis of Paediatric Psychosis

Psychotic symptoms in young children do not present as distinct delusions or hallucinations. Instead they take the form of subtle behavioural oddities, confusion and fearfulness. Here we present a rare case of sudden onset psychosis and discuss the symptomatology along with possible clinical conditions that may mimic the picture.

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin’s role in neuroinflammation and hippocampal biology.