A study of wills and will-making in the period 1500-1533 with special reference to the copy wills in the probate registers of the Archdeacon of Bedford 1489-1533

Historians sometimes use information derived from sources the nature and function of which they do not fully understand. Wills and testaments from the medieval and early modem periods provide a notable example of this practice; they have been used by historians for the information which they provide on a variety of subjects but have rarely been studied as documents in their own right. As a result, an understanding of the character of wills and testaments and of their utility for the historian has remained limited, and information derived from wills has not always been interpreted satisfactorily. This study involves the detailed examination of a group of Bedfordshire wills made over a thirty-three year period during the early sixteenth century with the intention of promoting a better understanding of this popular source of historical evidence. The seven hundred and eighty wills which form the nucleus of the study are recorded in the first three surviving registers of the court of the Archdeacon of Bedford. The information provided by the wills themselves will be evaluated in the context of the work of historians who have used information derived from wills, both from Bedfordshire and elsewhere, and in the context of early sixteenth-century law and custom. Particular attention is given to the interaction of the last will and testament with the medieval law of succession and to the problems which the complexity of the rules, principles and laws governing the succession to property provide for those who seek to interpret bequests of both personalty and realty

Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation–causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships

Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls.

BackgroundAuditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.MethodsASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.ResultsG-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.DiscussionThe excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies

Role of N-methyl-D-aspartate receptors in action-based predictive coding deficits in schizophrenia

Published in final edited form as:Biol Psychiatry. 2017 March 15; 81(6): 514–524. doi:10.1016/j.biopsych.2016.06.019.BACKGROUND: Recent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia. METHODS: In two separate studies, the N1 component of the event-related potential elicited by speech sounds during vocalization (talk) and passive playback (listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the crossover study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. Event-related potentials during the talk/listen task were obtained before infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy control volunteers were compared. RESULTS: N1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen’s d = 1.14) and schizophrenia (Cohen’s d = .85). CONCLUSIONS: Disruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia.This work was supported by AstraZeneca for an investigator-initiated study (DHM) and the National Institute of Mental Health Grant Nos. R01 MH-58262 (to JMF) and T32 MH089920 (to NSK). JHK was supported by the Yale Center for Clinical Investigation Grant No. UL1RR024139 and the US National Institute on Alcohol Abuse and Alcoholism Grant No. P50AA012879. (AstraZeneca for an investigator-initiated study (DHM); R01 MH-58262 - National Institute of Mental Health; T32 MH089920 - National Institute of Mental Health; UL1RR024139 - Yale Center for Clinical Investigation; P50AA012879 - US National Institute on Alcohol Abuse and Alcoholism)Accepted manuscrip

Aberrant activity in conceptual networks underlies N400 deficits and unusual thoughts in schizophrenia.

BackgroundThe N400 event-related potential (ERP) is triggered by meaningful stimuli that are incongruous, or unmatched, with their semantic context. Functional magnetic resonance imaging (fMRI) studies have identified brain regions activated by semantic incongruity, but their precise links to the N400 ERP are unclear. In schizophrenia (SZ), N400 amplitude reduction is thought to reflect overly broad associations in semantic networks, but the abnormalities in brain networks underlying deficient N400 remain unknown. We utilized joint independent component analysis (JICA) to link temporal patterns in ERPs to neuroanatomical patterns from fMRI and investigate relationships between N400 amplitude and neuroanatomical activation in SZ patients and healthy controls (HC).MethodsSZ patients (n = 24) and HC participants (n = 25) performed a picture-word matching task, in which words were either matched (APPLE→apple) by preceding pictures, or were unmatched by semantically related (in-category; IC, APPLE→lemon) or unrelated (out of category; OC, APPLE→cow) pictures, in separate ERP and fMRI sessions. A JICA "data fusion" analysis was conducted to identify the fMRI brain regions specifically associated with the ERP N400 component. SZ and HC loading weights were compared and correlations with clinical symptoms were assessed.ResultsJICA identified an ERP-fMRI "fused" component that captured the N400, with loading weights that were reduced in SZ. The JICA map for the IC condition showed peaks of activation in the cingulate, precuneus, bilateral temporal poles and cerebellum, whereas the JICA map from the OC condition was linked primarily to visual cortical activation and the left temporal pole. Among SZ patients, fMRI activity from the IC condition was inversely correlated with unusual thought content.ConclusionsThe neural networks associated with the N400 ERP response to semantic violations depends on conceptual relatedness. These findings are consistent with a distributed network underlying neural responses to semantic incongruity including unimodal visual areas as well as integrative, transmodal areas. Unusual thoughts in SZ may reflect impaired processing in transmodal hub regions such as the precuneus, leading to overly broad semantic associations

The prospects for increasing UK production of feedstocks for bioenergy

Bioenergy could play an important role in reducing UK greenhouse gas emissions to net zero by 2050, but biomass production and use will have to increase significantly. This research explores what potential there is for increasing biomass production, and how that increase could be delivered, using Yorkshire and Humberside (Y&H) as a case study. A mixed methods approach was used combining a biomass assessment, stakeholder interviews and policy analysis. Comparing the Y&H biomass potential with the regional bioenergy generation, identified biomass types with potential for greater production or use. Semi-structured interviews held with farmers, landowners, foresters, and industry experts were analysed using a framework based on Rogers’ Theory of Diffusion of Innovations. Policies to promote woodland creation and perennial energy crop (PEC) cultivation, identified from literature and the stakeholder interviews, were assessed using a policy Delphi, to produce recommendations for government action. Energy crops have the most potential to increase biomass production in the UK, and annual energy crops (e.g. maize and grass) are popular with farmers, but cultivation of the PECs miscanthus and short rotation coppice willow has stagnated because of limited markets, competitive cereal prices, the length of commitment required, and cultural barriers. Sustainably managed woodlands can deliver carbon sequestration, and woodfuel, but barriers to creation include the permanence of planting, loss of annual farming income, expense of planting and maintenance, and cultural divisions between forestry and farming. Although a considerable volume of poultry litter is produced in the UK, bioenergy use is constrained by the competing demand for organic fertiliser, and the high capital cost of on-farm combustion. Significant policy action will be needed in the UK to increase biomass supply. Demand side incentives could create a market for PEC biomass, support attractive long-term contracts, and stimulate growth of the full supply chain, while short term planting support could also be effective to drive adoption. Woodland creation could be driven by rewards for delivering carbon sequestration (a public good), and attractive grants to cover establishment costs and replace lost income. More information and education could overcome the traditional divide between farming and forestry. The new Environmental Land Management scheme in England (and corresponding schemes in the rest of the UK) will also be vital in delivering the landscape scale changes of land use needed to meet the UK ’s net zero targets, including the changes required to increase the domestic supply of biomass for bioenergy

The Neurophysiology of Auditory Hallucinations – A Historical and Contemporary Review

Electroencephalography and magnetoencephalography are two techniques that distinguish themselves from other neuroimaging methodologies through their ability to directly measure brain-related activity and their high temporal resolution. A large body of research has applied these techniques to study auditory hallucinations. Across a variety of approaches, the left superior temporal cortex is consistently reported to be involved in this symptom. Moreover, there is increasing evidence that a failure in corollary discharge, i.e., a neural signal originating in frontal speech areas that indicates to sensory areas that forthcoming thought is self-generated, may underlie the experience of auditory hallucinations