Online cognitive monitoring technology for people with Parkinson's disease and REM sleep behavioural disorder.

Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson's Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Background: Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. Methods: This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients' performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). Findings: The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r = 0.86, p < 0.001 and r = 0.81, p = 0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555) = 3.99; p < 0.001). Interpretation: Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. Funding: This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH (II-LB-0715-20006).

Psychedelic Cognition-The Unreached Frontier of Psychedelic Science.

Psychedelic compounds hold the promise of changing the face of neuroscience and psychiatry as we know it. There have been numerous proposals to use them to treat a range of neuropsychiatric conditions such as depression, anxiety, addiction and PTSD; and trials to date have delivered positive results in favor of the novel therapeutics. Further to the medical use, the wider healthy population is gaining interest in these compounds. We see a surge in personal use of psychedelic drugs for reasons not limited to spiritual enhancement, improved productivity, aiding the management of non-pathological anxiety and depression, and recreational interests. Notably, microdosing-the practice of taking subacute doses of psychedelic compounds-is on the rise. Our knowledge about the effects of psychedelic compounds, however, especially in naturalistic settings, is still fairly limited. In particular, one of the largest gaps concerns the acute effects on cognition caused by psychedelics. Studies carried out to date are riddled with limitations such as having disparate paradigms, small sample sizes, and insufficient breadth of testing on both unhealthy and healthy volunteers. Moreover, the studies are majoritarily limited to laboratory settings and do not assess the effects at multiple dosages within the same paradigm nor at various points throughout the psychedelic experience. This review aims to summarize the studies to date in relation to how psychedelics acutely affect different domains of cognition. In the pursuit of illuminating the current limitations and offering long-term, forward-thinking solutions, this review compares and contrasts findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.

Detecting axonal injury in individual patients after traumatic brain injury.

Poor outcomes after traumatic brain injury (TBI) are common yet remain difficult to predict. Diffuse axonal injury is important for outcomes, but its assessment remains limited in the clinical setting. Currently, axonal injury is diagnosed based on clinical presentation, visible damage to the white matter or via surrogate markers of axonal injury such as microbleeds. These do not accurately quantify axonal injury leading to misdiagnosis in a proportion of patients. Diffusion tensor imaging provides a quantitative measure of axonal injury in vivo, with fractional anisotropy often used as a proxy for white matter damage. Diffusion imaging has been widely used in TBI but is not routinely applied clinically. This is in part because robust analysis methods to diagnose axonal injury at the individual level have not yet been developed. Here, we present a pipeline for diffusion imaging analysis designed to accurately assess the presence of axonal injury in large white matter tracts in individuals. Average fractional anisotropy is calculated from tracts selected on the basis of high test-retest reliability, good anatomical coverage and their association to cognitive and clinical impairments after TBI. We test our pipeline for common methodological issues such as the impact of varying control sample sizes, focal lesions and age-related changes to demonstrate high specificity, sensitivity and test-retest reliability. We assess 92 patients with moderate-severe TBI in the chronic phase (≥6 months post-injury), 25 patients in the subacute phase (10 days to 6 weeks post-injury) with 6-month follow-up and a large control cohort (n = 103). Evidence of axonal injury is identified in 52% of chronic and 28% of subacute patients. Those classified with axonal injury had significantly poorer cognitive and functional outcomes than those without, a difference not seen for focal lesions or microbleeds. Almost a third of patients with unremarkable standard MRIs had evidence of axonal injury, whilst 40% of patients with visible microbleeds had no diffusion evidence of axonal injury. More diffusion abnormality was seen with greater time since injury, across individuals at various chronic injury times and within individuals between subacute and 6-month scans. We provide evidence that this pipeline can be used to diagnose axonal injury in individual patients at subacute and chronic time points, and that diffusion MRI provides a sensitive and complementary measure when compared to susceptibility weighted imaging, which measures diffuse vascular injury. Guidelines for the implementation of this pipeline in a clinical setting are discussed.

Memory reconsolidation impairments in sign-tracking to an audiovisual compound stimulus.

Studies of memory reconsolidation of pavlovian memories have typically employed unimodal conditioned stimuli, despite the use of multimodal compound stimuli in other settings. Here we studied sign-tracking behaviour to a compound audiovisual stimulus. First, we observed not unexpectedly that sign-tracking was poorer to the audiovisual compound than to unimodal visual stimuli. Then, we showed that, depending on the parameters of compound stimulus re-exposure at memory reactivation, systemic MK-801 treatment either impaired extinction to improve sign-tracking at test, or disrupted reconsolidation to impair test behaviour. When memory reactivation consisted of re-exposure to only the auditory component of the compound stimulus, we observed sign-tracking impairments following MK-801 treatment, but only under certain test conditions. This was in contrast to the consistent impairment following reactivation with the full audiovisual compound. Moreover, the parameters of auditory stimulus presentation to enable MK-801-induced impairment at test varied depending on whether the stimulus was presented within or outside the training context. These findings suggest that behaviour under the control of appetitive pavlovian compound stimuli can be modulated by targeting both extinction and reconsolidation, and that it is not necessary to re-expose to the full compound stimulus in order to achieve a degree of modulation of behaviour.

Myeloperoxidase, a possible biomarker for the early diagnosis of cardiac diastolic dysfunction with preserved ejection fraction.

The current study was conducted on a sample of 91 patients diagnosed with diastolic dysfunction (DD) with preserved systolic function caused by a painful chronic ischaemic cardiopathy - angina pectoris stable at the effort. The diagnosis was established following anamnesis, electrocardiogram, and echocardiography. Myeloperoxidase (MPO) serum levels were assessed in all patients and then these values were correlated with some of the echocardiography parameters that proved the mentioned diagnosis. In conclusion, the execution of this investigation triad (electrocardiogram, echocardiography, and MPO) allows: Stratifying the patients depending on the disease risk by early detecting of any possible DD with preserved systolic function. The use of the MPO increased circulating levels as a biomarker for diagnosis and risk due to the statistically significant correlation between those and the results of the other two aforementioned paraclinical investigation.

Gamma-glutamyltransferase, possible novel biomarker in colon diverticulosis: a case-control study.

The gamma-glutamyltransferase (GGT) is recognized in medical practice as a useful indicator for the detection of liver lesions, especially those induced by the excessive consumption of alcoholic or cholesterol-associated drinks. The present study, although it includes a very small number of cases diagnosed with colon diverticulosis-diverticulitis associated with polyposis at the same intestinal level, identifies the presence of increased circulating concentrations of this enzyme in the serum. Its serum levels are tracked "dynamically" throughout a year after the diagnosis and start of the therapy. The study calls into question the release of the enzyme from the edge of the enterocytes' brush-like edge, leading to the pathogenic disturbance of regional redox homeostasis. The hypothesis gives the circulating values of GGT predictive value for cellular oxidative stress, as well as for indirectly expressing the glutathione level in cytosol.

Haemolytic anaemia and hepatocitolysis associated with hypermagnesaemia by repeated exposures to copper-calcium fungicides.

For the medical practice, our manuscript acts as a signal, despite only presenting three cases which feature the association between hepatocytolysis, haemolysis and hypermagnesaemia. This clinical-biologic triad was highlighted with the workers who through the nature of their profession were exposing themselves periodically to vapours which contained copper sulphate neutralised with calcium hydroxide, a fungicide used for fruit trees. We are exclusively assessing the haematological perturbation. In this aetiological context, the generating mechanism for haemolysis is very probable biochemical, where hypercupraemia interferes with cellular antioxidant defence mechanisms. Hypothetically, the role of the redox homeostasis disorder in the intravascular destruction of erythrocytes is sustained, and particularly the coexistence of cell cytolysis in the medullary erythroid compartment, which can be assimilated with a possible ineffective erythropoiesis.