Is Online Motor Control Really Impaired In Parkinson\u27s Disease?

Patients with Parkinson’s disease (PD) are thought to be selectively impaired in consciously-mediated online automatic motor control, whereas the ability to perform subconscious online adjustments remains intact. This present study evaluates the hypothesis that the previously alleged deficits in online motor control in PD are not due to the consciousness of the correction, but rather are attributable to aspects of the prior experimental designs disproportionately penalizing patients for PD-related bradykinesia. Here, we implemented a modified traditional double-step paradigm to investigate consciously-mediated online motor control in PD, in a manner that would be unconfounded by disease-related bradykinesia. Further, we investigated the effects of dopamine-replacement therapy on performance. We found that PD patients (n=12) and healthy-matched controls (n=12) were equal in performing automatic online corrections whether or not these corrections were consciously perceived, and their performance was unaffected by dopaminergic therapy. These findings inform our understanding of automatic motor control in PD

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia with Proton Magnetic Resonance Spectroscopy Brain Glutamate Level:A Mega-analysis of Individual Participant-Level Data

Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.Data Sources: The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome∗ or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.Study Selection: In total, 45 1H-MRS studies contributed data.Data Extraction and Synthesis: Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.Main Outcomes and Measures: Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).Results: In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9= 4.311, P =.04) and Glx (F1,1079.2= 5.287, P =.02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9= 3.622, P =.06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4= 47.533, P &lt;.001; cerebrospinal fluid-corrected Glu, F1,1216.7= 5.610, P =.02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.Conclusions and Relevance: Findings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia..</p

Perioperative fluid management and associated complications in children receiving kidney transplants in the UK

Background: Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. Methods: Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. Results: Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. Conclusions: This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. Graphical Abstract: A higher resolution version of the Graphical abstract is available as Supplementary information [Figure not available: see fulltext.]

Automatic online motor control is intact in Parkinson’s disease with and without perceptual awareness

In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson’s disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients (n = 14) and healthy controls (n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls’. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses

Resource Guide for Addiction and Mental Health Care Consumers: Answering Questions about Insurance Coverage and Parity for Addiction and Mental Health Care Services

Navigating the maze of health insurance coverage can be difficult. For individuals with addiction or mental illness, the process of getting treatment approved and paid for by health insurance can be overwhelming. As a result, many people give up when their health insurance company denies coverage for needed services. This Guide can help people learn how to access health insurance and use their coverage to pay for treatment. This Guide also provides a basic explanation of consumers’ rights under the federal Mental Health Parity and Addiction Equity Act

Longitudinal Structural MRI Findings in Individuals at Genetic and Clinical High Risk for Psychosis: A Systematic Review

Background: Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. However, longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset. Methods: We conducted a systematic review to determine if brain trajectories differ between (i) those with psychotic experiences (PE), genetic (GHR) or clinical high risk (CHR), compared to healthy volunteers, and (ii) those who transition to psychosis compared to those who do not. Results: Thirty-eight studies measured gray matter and 18 studies measured white matter in 2,473 high risk subjects and 990 healthy volunteers. GHR, CHR, and PE subjects show an accelerated decline in gray matter primarily in temporal, and also frontal, cingulate and parietal cortex. In those who remain symptomatic or transition to psychosis, gray matter loss is more pronounced in these brain regions. White matter volume and fractional anisotropy, which typically increase until early adulthood, did not change or reduced in high risk subjects in the cingulum, thalamic radiation, cerebellum, retrolenticular part of internal capsule, and hippocampal–thalamic tracts. In those who transitioned, white matter volume and fractional anisotropy reduced over time in the inferior and superior fronto-occipital fasciculus, corpus callosum, anterior limb of the internal capsule, superior corona radiate, and calcarine cortex. Conclusion: High risk subjects show deficits in white matter maturation and an accelerated decline in gray matter. Gray matter loss is more pronounced in those who transition to psychosis, but may normalize by early adulthood in remitters

Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

Background: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. Aims: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. Methods: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond–Lader Visual Analogue Scales). Results: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. Conclusions: We found no indication of an effect of GTN on symptoms of psychosis or cognition

Trying Cases in the Media: Legal Ethics, Fair Trials and Free Press

The 2000 symposium consisted of a panel discussion which used role-playing and a mock trial to highlight the issues of lawyer/litigant comments to the press before and during trial and the dilemma of journalists confronted by court demands for documents, testimony, or sources of information obtained in the course of gathering news on pending trials. Participants included: As United States Attorney for the Eastern District of Freedonia: John Douglas, Associate Professor of Law at the University of Richmond. As Freedonia criminal defense lawyer: Gerald Zerkin, Private Defense Attorney. As investigative journalist: Steve Nash, Associate Professor of Journalism at the University of Richmond. As federal judge: Judge Margaret P. Spencer, Virginia Circuit Court Judge. As media attorney: Craig Thomas Merritt, Attorney. As first amendment attorney: J. Joshua Wheeler, Attorney and Director of Programs for the Thomas Jefferson Center for the Protection of Free Expression, and adjunct professor at University of Virginia. As Chief Justice: Paul D. Carrington, The Chadwick Professor of Law at Duke University. As Associate Justices of the United States Supreme Court: C. Thomas Dienes, Patricia Roberts Harris Professor of Law at George Washington University\u27s Law School; John E. Nowak, David C. Baum Professor of Law at the University of Illinois; Molly Delea, third-year law student, University of Richmond School of Law; Kate Murray, third-year law student, University of Richmond School of Law; Thomas Queen, third-year law student, University of Richmond School of Law; and Courtney Sydnor, third-year law student, University of Richmond School of Law

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders