Button-pressing affects P300 amplitude and scalp topography

Abstract Background: Scant and equivocal research exists examining the effects of button-pressing on P300. Button-pressing may decrease P300 latency and amplitude. The melding of motor potentials and P300 may also confound studies of P300 topography, such as studies of temporal scalp-area asymmetries in schizophrenia. Method: P300 was measured on button-press and silent-count tasks in control subjects. An estimate of motor activity was constructed from a simple reaction time task, with reaction times matched to the button-press task. The motor estimate was subtracted from the buttonpress P300 to assess Results: P300 was smaller and its topography different in the button-pressing task relative to silent-counting. The motor-correction procedure generated a P300 with normal topography. Comparison of the button-press P300 in controls to the silent-count P300 in schizophrenia patients reduced a signi®cant lateral asymmetry to trend level. This asymmetry was signi®cant after the correction procedure. Conclusions: Button-pressing generates smaller P300 than silent-counting. Also, P300 topography in button-pressing tasks is confounded by motor potentials. The distortion can be corrected with a motor potential estimate. Motor potentials can occlude differences in P300 topography between groups.

Semantic bias, homograph comprehension, and event-related potentials in schizophrenia

Objectives: It is controversial whether a semantic processing bias for strong associates is present in schizophrenia, and unknown whether the language abnormalities observed in schizophrenia can be attributed to dysfunctions early or late in cognitive processing. Combined behavioral and event-related potential (ERP) data can indicate the nature and timing of such abnormalities. Methods: Sensibility judgements of dominant and subordinate homograph sentences were measured in 12 schizophrenia patients and 13 normal controls. ERPs were recorded to the disambiguating sentence-ending word. Results: All subjects showed greatest misinterpretation of subordinate homograph sentences, but schizophrenia patients particularly misinterpreted these sentence types. For control subjects, subordinate homograph sentences that were classified as nonsensical showed greater N400 than those classified as sensible. By contrast, the N400 of patients was large, regardless of the sensibility judgement – patients’ brains initially responded to all subordinate sentences as if nonsensical. These data are consonant with a semantic bias. However, the patients’ N400 to dominant homograph sentence endings was also larger than that of controls, a finding not consonant with a semantic bias. Conclusions: The behavioral results indicate a selective comprehension abnormality in schizophrenia dependent on the content of verbal memory. The ERP results suggest a pervasive contextual memory failure. A semantic activation decay model is proposed to explain these results

Event-related potentials elicited during a context-free homograph task in normal versus schizophrenic subjects

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading “THE NOUN WAS ADJECTIVE/VERB” were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context

Progressive and Interrelated Functional and Structural Evidence of Post-Onset Brain Reduction in Schizophrenia

Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes. Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally. Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up). Setting: A private psychiatric hospital. Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status. Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging. Main Outcome Measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes. Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=−0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04). Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention

Workforce predictive risk modelling: development of a model to identify general practices at risk of a supply−demand imbalance

Objective: This study aimed to develop a risk prediction model identifying general practices at risk of workforce supply–demand imbalance. Design: This is a secondary analysis of routine data on general practice workforce, patient experience and registered populations (2012 to 2016), combined with a census of general practitioners’ (GPs’) career intentions (2016). Setting/Participants: A hybrid approach was used to develop a model to predict workforce supply–demand imbalance based on practice factors using historical data (2012–2016) on all general practices in England (with over 1000 registered patients n=6398). The model was applied to current data (2016) to explore future risk for practices in South West England (n=368). Primary outcome measure: The primary outcome was a practice being in a state of workforce supply–demand imbalance operationally defined as being in the lowest third nationally of access scores according to the General Practice Patient Survey and the highest third nationally according to list size per full-time equivalent GP (weighted to the demographic distribution of registered patients and adjusted for deprivation). Results: Based on historical data, the predictive model had fair to good discriminatory ability to predict which practices faced supply–demand imbalance (area under receiver operating characteristic curve=0.755). Predictions using current data suggested that, on average, practices at highest risk of future supply–demand imbalance are currently characterised by having larger patient lists, employing more nurses, serving more deprived and younger populations, and having considerably worse patient experience ratings when compared with other practices. Incorporating findings from a survey of GP’s career intentions made little difference to predictions of future supply–demand risk status when compared with expected future workforce projections based only on routinely available data on GPs’ gender and age. Conclusions: It is possible to make reasonable predictions of an individual general practice’s future risk of undersupply of GP workforce with respect to its patient population. However, the predictions are inherently limited by the data available

First-Episode Schizophrenic Psychosis Differs From First-Episode Affective Psychosis and Controls in P300 Amplitude Over Left Temporal Lobe

Background: Schizophrenia is associated with central (sagittal) midline reductions of the P300 cognitive event-related potential and topographic asymmetry of P300, with reduced left temporal voltage. This P300 asymmetry is, in turn, linked to tissue volume asymmetry in the posterior superior temporal gyrus. However, it is unknown whether P300 asymmetry is specific to schizophrenia and whether central and lateral P300 abnormalities are due to chronic morbidity, neuroleptic medication, and/or hospitalization, or whether they are present at the onset of illness. Methods: P300 was recorded in first-episode schizophrenia, first-episode affective psychosis, and control subjects (n=14 per group). Subjects silently counted rare (15%) target tones (1.5 kHz) among trains of standard tones (1.0 kHz). Averages were constructed from brain responses to target tones. Results: Peak amplitude of P300 and integrated voltage over 300 to 400 milliseconds were significantly different between first-episode schizophrenics and controls over the posterior sagittal midline of the head. First-episode schizophrenics displayed smaller amplitudes over the left temporal lobe than first-episode affective psychotics and controls, but the groups showed no differences over the right temporal lobe. Conclusions: Left-sided P300 abnormality in first-episode schizophrenia relative to first-episode affective psychosis and controls suggests that P300 asymmetry is specific to schizophrenic psychosis and present at initial hospitalization. This P300 asymmetry suggests left temporal lobe dysfunction at the onset of schizophrenia

Cavum septi pellucidi in first-episode schizophrenia and first-episode affective psychosis: an MRI study

A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia

A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala–hippocampal complex in chronic schizophrenia

A progressive post-onset decrease in gray matter volume 1.5 years after first hospitalization in schizophrenia has been shown in superior temporal gyrus (STG). However, it is still controversial whether progressive volume reduction occurs in chronic schizophrenia in the STG and amygdala– hippocampal complex (AHC), structures found to be abnormal in chronic schizophrenia. These structures were measured at two time points in 16 chronic schizophrenia patients and 20 normal comparison subjects using manual tracing with high spatial resolution magnetic resonance imaging (MRI).Average interscan interval was 3.1 years for schizophrenia patients and 1.4 years for healthy comparison subjects. Cross-sectional comparisons showed smaller relative volumes in schizophrenia compared with controls in posterior STG and AHC. An ANCOVA with interscan interval as a covariate showed there was no statistically significant progression of volume reduction in either the STG or AHC in the schizophrenia group compared with normal subjects. In the schizophrenia group, volume change in the left anterior AHC significantly correlated with PANSS negative symptoms. These data, and separately reported first episode data from our laboratory, suggest marked progression at the initial stage of schizophrenia, but less in chronic schizophrenia

Policies and strategies to retain and support the return of experienced GPs in direct patient care: the ReGROUP mixed-methods study

Background: UK general practice faces a workforce crisis, with general practitioner (GP) shortages, organisational change, substantial pressures across the whole health-care system and an ageing population with increasingly complex health needs. GPs require lengthy training, so retaining the existing workforce is urgent and important. Objectives: (1) To identify the key policies and strategies that might (i) facilitate the retention of experienced GPs in direct patient care or (ii) support the return of GPs following a career break. (2) To consider the feasibility of potentially implementing those policies and strategies. Design: This was a comprehensive, mixed-methods study. Setting: This study took place in primary care in England. Participants: General practitioners registered in south-west England were surveyed. Interviews were with purposively selected GPs and primary care stakeholders. A RAND/UCLA Appropriateness Method (RAM) panel comprised GP partners and GPs working in national stakeholder organisations. Stakeholder consultations included representatives from regional and national groups. Main outcome measures: Systematic review – factors affecting GPs’ decisions to quit and to take career breaks. Survey – proportion of GPs likely to quit, to take career breaks or to reduce hours spent in patient care within 5 years of being surveyed. Interviews – themes relating to GPs’ decision-making. RAM – a set of policies and strategies to support retention, assessed as ‘appropriate’ and ‘feasible’. Predictive risk modelling – predictive model to identify practices in south-west England at risk of workforce undersupply within 5 years. Stakeholder consultation – comments and key actions regarding implementing emergent policies and strategies from the research. Results: Past research identified four job-related ‘push’ factors associated with leaving general practice: (1) workload, (2) job dissatisfaction, (3) work-related stress and (4) work–life balance. The survey, returned by 2248 out of 3370 GPs (67%) in the south-west of England, identified a high likelihood of quitting (37%), taking a career break (36%) or reducing hours (57%) within 5 years. Interviews highlighted three drivers of leaving general practice: (1) professional identity and value of the GP role, (2) fear and risk associated with service delivery and (3) career choices. The RAM panel deemed 24 out of 54 retention policies and strategies to be ‘appropriate’, with most also considered ‘feasible’, including identification of and targeted support for practices ‘at risk’ of workforce undersupply and the provision of formal career options for GPs wishing to undertake portfolio roles. Practices at highest risk of workforce undersupply within 5 years are those that have larger patient list sizes, employ more nurses, serve more deprived and younger populations, or have poor patient experience ratings. Actions for national organisations with an interest in workforce planning were identified. These included collection of data on the current scope of GPs’ portfolio roles, and the need for formal career pathways for key primary care professionals, such as practice managers. Limitations: The survey, qualitative research and modelling were conducted in one UK region. The research took place within a rapidly changing policy environment, providing a challenge in informing emergent policy and practice. Conclusions: This research identifies the basis for current concerns regarding UK GP workforce capacity, drawing on experiences in south-west England. Policies and strategies identified by expert stakeholders after considering these findings are likely to be of relevance in addressing GP retention in the UK. Collaborative, multidisciplinary research partnerships should investigate the effects of rolling out some of the policies and strategies described in this report. Study registration: This study is registered as PROSPERO CRD42016033876 and UKCRN ID number 20700. Funding: The National Institute for Health Research Health Services and Delivery Research programme