Personalised physiological medicine: Orthostatic hypotension

\ua9 2022 The Authors. Orthostatic hypotension (OH) is a very common and debilitating condition, characterised by a significant drop in blood pressure (BP) on standing upright. Multiple neuro-cardiovascular mechanisms should stabilise BP when moving to an upright position but in OH, BP decline results from dysfunction of neuro-cardiovascular mechanisms. With the advent of non-invasive, beat-to-beat BP measurement, the detailed postural BP profile presents an opportunity to explore the underlying pathological deficits seen in OH. To date, several distinct clusters of postural BP drop have been identified, typically defined by the rate and duration of BP decline and the degree of recovery. The morphology of the BP drop may reflect the underlying cardiac output and peripheral vascular resistance. There are three principal treatment strategies for OH; conservative management, fludrocortisone or midodrine. As each of these therapies have different therapeutic mechanisms, in this review we hypothesise how they could be used in a more targeted manner to treat the underlying physiological deficit - conservative management for ‘initial drop, quick recovery’, fludrocortisone for ‘medium drop, slow recovery/venular-deficit’ and midodrine for ‘large drop, non-recovery/arteriolar-deficit’

Language and theory of mind in autism spectrum disorder : the relationship between complement syntax and false belief task performance.

This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of “hacking out” solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a “memory for complements” task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered

Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR) environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants). We measured walking kinematics (joint-angles, velocity profiles) and motor performance (end-point-compensation, trajectory-deviations). Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS) uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation

Artificial intelligence driven clustering of blood pressure profiles reveals frailty in orthostatic hypertension

\ua9 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.Gravity, an invisible but constant force, challenges the regulation of blood pressure when transitioning between postures. As physiological reserve diminishes with age, individuals grow more susceptible to such stressors over time, risking inadequate haemodynamic control observed in orthostatic hypotension. This prevalent condition is characterized by drops in blood pressure upon standing; however, the contrary phenomenon of blood pressure rises has recently piqued interest. Expanding on the currently undefined orthostatic hypertension, our study uses continuous non-invasive cardiovascular data to explore the full spectrum of blood pressure profiles and their associated frailty outcomes in community-dwelling older adults. Given the richness of non-invasive beat-to-beat data, artificial intelligence (AI) offers a solution to detect the subtle patterns within it. Applying machine learning to an existing dataset of community-based adults undergoing postural assessment, we identified three distinct clusters (iOHYPO, OHYPO and OHYPER) akin to initial and classic orthostatic hypotension and orthostatic hypertension, respectively. Notably, individuals in our OHYPER cluster exhibited indicators of frailty and sarcopenia, including slower gait speed and impaired balance. In contrast, the iOHYPO cluster, despite transient drops in blood pressure, reported fewer fallers and superior cognitive performance. Surprisingly, those with sustained blood pressure deficits outperformed those with sustained rises, showing greater independence and higher Fried frailty scores. Working towards more refined definitions, our research indicates that AI approaches can yield meaningful blood pressure morphologies from beat-to-beat data. Furthermore, our findings support orthostatic hypertension as a distinct clinical entity, with frailty implications suggesting that it is worthy of further investigation

Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders

Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatoryinhibitory balance underlies enhanced neural responses to coherent motion in ASD

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

Exercise referral for drug users aged 40 and over: results of a pilot study in the UK.

OBJECTIVES: To test whether older drug users (aged 40 and over) could be recruited to an exercise referral (ER) scheme, to evaluate the feasibility and acceptability and measure the impact of participation on health. DESIGN: Observational pilot. SETTING: Liverpool, UK. PARTICIPANTS: (1) 12 men and 5 women recruited to ER. (2) 7 specialist gym instructors. OUTCOME MEASURES: Logistic feasibility and acceptability of ER and associated research, rate of recruitment, level of participation over 8 weeks and changes in health. RESULTS: 22 gym inductions were arranged (recruitment time: 5 weeks), 17 inductions were completed and 14 participants began exercising. Attendance at the gym fluctuated with people missing weeks then re-engaging; in week 8, seven participants were in contact with the project and five of these attended the gym. Illness and caring responsibilities affected participation. Participants and gym instructors found the intervention and associated research processes acceptable. In general, participants enjoyed exercising and felt fitter, but would have welcomed more support and the offer of a wider range of activities. Non-significant reductions in blood pressure and heart rate and improvements in metabolic equivalents (METs; a measure of fitness) and general well-being were observed for eight participants who completed baseline and follow-up assessments. The number of weeks of gym attendance was significantly associated with a positive change in METs. CONCLUSIONS: It is feasible to recruit older drug users into a gym-based ER scheme, but multiple health and social challenges affect their ability to participate regularly. The observed changes in health measures, particularly the association between improvements in METs and attendance, suggest further investigation of ER for older drug users is worthwhile. Measures to improve the intervention and its evaluation include: better screening, refined inclusion/exclusion criteria, broader monitoring of physical activity levels, closer tailored support, more flexible exercise options and the use of incentives

The Edinburgh Social Cognition Test (ESCoT):Examining the effects of age on a new measure of theory of mind and social norm understanding

<div><p>Current measures of social cognition have shown inconsistent findings regarding the effects of healthy aging. Moreover, no tests are currently available that allow clinicians and researchers to examine cognitive and affective theory of mind (ToM) and understanding of social norms within the same test. To address these limitations, we present the Edinburgh Social Cognition Test (ESCoT) which assesses cognitive and affective ToM and inter- and intrapersonal understanding of social norms. We examined the effects of age, measures of intelligence and the Broader Autism Phenotype (BAP) on the ESCoT and established tests of social cognition. Additionally, we investigated the convergent validity of the ESCoT based on traditional social cognition measures. The ESCoT was administered alongside Reading the Mind in Films (RMF), Reading the Mind in Eyes (RME), Judgement of Preference and Social Norm Questionnaire to 91 participants (30 aged 18–35 years, 30 aged 45–60 years and 31 aged 65–85 years). Poorer performance on the cognitive and affective ToM ESCoT subtests were predicted by increasing age. The affective ToM ESCoT subtest and RMF were predicted by gender, where being female predicted better performance. Unlike the ESCoT, better performance on the RMF was predicted by higher verbal comprehension and perceptual reasoning abilities, while better performance on the RME was predicted by higher verbal comprehension scores. Lower scores on inter-and intrapersonal understanding of social norms were both predicted by the presence of more autism-like traits while poorer interpersonal understanding of social norms performance was predicted by increasing age. These findings show that the ESCoT is a useful measure of social cognition and, unlike established tests of social cognition, performance is not predicted by measures of verbal comprehension and perceptual reasoning. This is particularly valuable to obtain an accurate assessment of the influence of age on our social cognitive abilities.</p></div

Smoking patterns and stimulus control in intermittent and daily smokers

Intermittent smokers (ITS) - who smoke less than daily - comprise an increasing proportion of adult smokers. Their smoking patterns challenge theoretical models of smoking motivation, which emphasize regular and frequent smoking to maintain nicotine levels and avoid withdrawal, but yet have gone largely unexamined. We characterized smoking patterns among 212 ITS (smoking 4-27 days per month) compared to 194 daily smokers (DS; smoking 5-30 cigarettes daily) who monitored situational antecedents of smoking using ecological momentary assessment. Subjects recorded each cigarette on an electronic diary, and situational variables were assessed in a random subset (n = 21,539 smoking episodes); parallel assessments were obtained by beeping subjects at random when they were not smoking (n = 26,930 non-smoking occasions). Compared to DS, ITS' smoking was more strongly associated with being away from home, being in a bar, drinking alcohol, socializing, being with friends and acquaintances, and when others were smoking. Mood had only modest effects in either group. DS' and ITS' smoking were substantially and equally suppressed by smoking restrictions, although ITS more often cited self-imposed restrictions. ITS' smoking was consistently more associated with environmental cues and contexts, especially those associated with positive or "indulgent" smoking situations. Stimulus control may be an important influence in maintaining smoking and making quitting difficult among ITS. © 2014 Shiffman et al