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Aims In schizophrenia, disorganisation and impoverished mental activity (as described in the classical descriptions by Kraepelin and Bleuler) together with impaired cognitive function, predict persisting functional impairment (Liddle, 2019). We propose that in schizophrenia, four ‘classical’ features (disorganisation, impoverished mental activity, cognitive dysfunction, and impaired role-functioning) arise from a shared pathophysiological process that increases risk of persisting functional impairment. We also propose that this shared process creates a risk of subsequent episodic reality distortion (delusions and hallucinations). In the current work, we investigate whether a single latent variable accounts for the shared variance in the four ‘classical’ features. We also investigate whether the severity of this latent variable based on assessment of long-standing classical symptoms predicts severity of current reality distortion. Methods We performed maximum likelihood factor analysis of disorganisation, impoverishment, cognition and role-function in three separate samples of patients (n = 54, n = 128, n = 64) with DSM diagnosed schizophrenia, schizo-affective disorder or bipolar disorder. In the first two samples, we quantified current disorganisation and impoverished mental activity using the Positive and Negative Syndrome Scale (PANSS). In the third, we scored persistent disorganisation and impoverished mental activity according to Symptoms & Signs of Psychosis Illness (SSPI) based on systematic examination of case records. We assessed cognition using the Digit Symbol Substitution Test (DSST) and role-function using the Social & Occupational functioning scale (in two studies) and the Personal & Social Performance scale (in one study). We quantified current reality distortion by summing SSPI scores for current delusions and hallucinations. Results In each of the three studies, a single latent variable accounted for more than 50% of variance. Loadings were similar whether current or persistent symptoms were used. The latent variable derived from persistent symptom scores correlated significantly with current reality distortion. Conclusion This series of studies provide further evidence that disorganisation, impoverished mental activity, cognitive impairment and impaired role function share substantial variance, consistent with the proposal that they reflect a core pathophysiological process underlying ‘classical’ schizophrenia. Furthermore, our findings are consistent with the hypothesis that over time, this pathophysiological process increases the risk of episodic reality distortion. However, these were all cross-sectional studies, and need to be confirmed using longitudinal data. Our findings have potential clinical and research implications including development of a custom-made clinical tool to quantify the core deficit as well as investigating targeted interventions employing medication or neuromodulation.

BackgroundDepression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment—a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses. ObjectiveThe aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment. MethodsThe study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity. ResultsRecruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023. ConclusionsThis trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients. Trial RegistrationISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644 International Registered Report Identifier (IRRID)DERR1-10.2196/31925

Introduction The BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in adults with moderate to severe treatment resistant depression.Methods and analysis The study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (1) cgiTBS or (2) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the UK. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined.Ethics and dissemination Ethical approval was granted by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. The results of the study will be published in relevant peer-reviewed journals, and then through professional and public conferences and media. Further publications will explore patient experience, moderators and mediators of outcome and mechanism of action.Trial registration number ISRCTN19674644

On the battlefield, it was the soldier-horse relationship that formed soldier and horse into an effective weapon against the enemy. At home, portrayals of this relationship enabled the British people to imagine the realities of war. Reality and representation co-existed in a blending of past and present that combined traditional notions of warfare with the modern battlefield. Increasingly, this imagery represented the many soldiers and horses of the ranks who, although humble, were striving every day to win the War. Images, such as Fortunino Matania's Good-bye, Old Man, allowed those at home to imagine their own loved ones in the soldier's compassion for his horse's plight. These messages of humanity and compassion would prove equally valuable when the process of national mourning and reconciliation began. [ABSTRACT FROM AUTHOR]

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A Promising lad Winston S. Churchill. Vol. 5, 1922–1939 By Martin Gilbert (Heinemann, London, 1976), £10.75, 1168 pages Reviewed by Ronald Lewin. Churchill and Morton: Correspondence between Major Sir Desmond Morton and R. W. Thompson Foreword by Captain S. W. Roskill (Hodder and Stoughton, London, 1976), £5.25, 223 pages Reviewed by Ronald Lewin. Douglas Haig By E. K. G. Sixsmith (Weidenfeld and Nicolson, London, 1976), £5.95, 212 pages Reviewed by Keith Simpson. A Prince of Our Disorder By John E. Mack (Weidenfeld and Nicolson, London, 1976), £6.95, 561 pages Reviewed by A. S. Higgs. Nimitz By E. B. Potter (Naval Institute Press, Annapolis, 1976), 491 pages (Patrick Stephens, Cambridge) Reviewed by Ronald Spector. Hitler's Generals By Richard Brett-Smith (Osprey, London, 1976), £5.95, 306 pages Reviewed by Bryan Watkins. The Shadow of the Winter Palace: the Drift to Revolution 1828–1917 By Edward Crankshaw (Macmillan, London, 1976), 429 pages Reviewed by R. F. Leslie. Wind in the Tower: Mao Tse-tung and the Chinese Revolution 1949–1975 By Han Suyin (Jonathan Cape, London, 1976), £6.50, 392 pages Reviewed by David Chambers. War in the Shadows, the Guerrilla in History By Robert B. Asprey (Macdonald and Jane's, London, 1976), £15, 1,615 pages Reviewed by Peter Janke. The Death of British Democracy: a Study of Britain's Political Present and Future By Stephen Haseler (Elek Books, London, 1976), £5.95, 262 pages Reviewed by Neville Trotter. Soviet Strategy in Europe Edited by Richard Pipes (Macdonald and Jane's, London, 1976), £9.75, 316 pages Reviewed by P. H. C. Hayward. 1976 Year Book on International Communist Affairs Edited by Richard F. Star (Hoover Institution Press, Stamford, California, 1976), 636 pages, $25 Reviewed by Peter Janke. Society, defence and détente: War, Economy and the Military Mind Edited by Geoffrey Best and Andrew Wheatcroft (Croom Helm, London, 1976), £5.95, 136 pages Reviewed by Brian Bond Society, defence and détente: Détente Edited by G. R. Urban (Temple Smith, London, 1976), £8.00, 368 pages Reviewed by David Bolton. Society, defence and détente: The Management of Defence Edited by Laurence Martin (Macmillan, London, 1976), £6.95, 133 pages Reviewed by David Bolton. The Dynamics of the Nuclear Balance (Revised Edition) By Albert Legault and George Lindsey (Cornell University Press, London), £10.15, 283 pages Reviewed by Edgar Feuchtwanger. India's Nuclear Option: Atomic Diplomacy and Decision Making By Ashok Kapur (Praeger Special Studies, Martin Robertson, London), £13.05, 295 pages Reviewed by Edgar Feuchtwanger. Germany and the Politics of Nuclear Weapons By Catherine McArdle Kelleher (Columbia University Press, London), £9.40, 372 pages Reviewed by Edgar Feuchtwanger. For want of ball-bearings…: The Blockade Busters By Ralph Barker (Chatto & Windus, London, 1976), £5.00, 224 pages Reviewed by Peter Dickens For want of ball-bearings…: Convoy: the Battle for Convoys SC122 and HX229 By Martin Middlebrook (Allen Lane, London, 1976), £4.95, 378 pages Reviewed by Donald Macintyre. The military—old style: Poor Bloody Infantry: a Memoir of the First World War By W. H. A. Groom (William Kimber, London, 1976), £3.95, 185 pages Reviewed by James Marshall-Cornwall. The military—old style: Eye-deep in Hell: the Western Front 1914–18 By John Ellis (Croom Helm, London, 1976), £5.95, 207 pages Reviewed by James Marshall-Cornwall. The military—old style: Men of Gallipoli By Peter Liddle (Allen Lane, London, 1976), £6.50, 320 pages Reviewed by P. H. C. Hayward. The military—new style: Coups and Army Rule in Africa: Studies in Military Style By Samuel Decalo (Yale University Press: New Haven and London), £11.55 cloth, £3.50 paperback, 284 pages Reviewed by A. Clayton. The military—old style: The Military in the Third World By Gavin Kennedy (Duckworth, London), £3.50, 369 pages Reviewed by A. Clayton. Land strategy and tactics: The North African Landings 1942: a Strategic Decision By Keith Sainsbury (Davis-Poynter, London, 1976), £5.00, 215 pages Reviewed by John Terraine. Land strategy and tactics: The Art of Blitzkrieg By Charles Messenger (Ian Allan, London, 1976), £4.50, 254 pages Reviewed by Bryan Watkins. Strategy without Slide-Rule By Barny D. Powers (Croom Helm, London, 1976), £8.95, 295 pages Reviewed by C. N. Foxley-Norris. Fighter Pilot—a Self Portrait By George Barclay, edited by Humphrey Wynn (William Kimber, London, 1976), £4.50, 224 pages Reviewed by Danis Crowley-Milling. Beaufighter at War By Chaz Bowyer (Ian Allan, London, 1976), £4.95, 160 pages Reviewed by C. N. Foxley-Norris. The F4 Phantom II and the United States Sixth Fleet in the Mediterranean Sea By Franz-Josef Giehl (Vantage Press, New York, 1976), S7.50, 218 pages Reviewed by John Huston. Attack Warning Red; the Royal Observer Corps and the Defence of Britain 1925 to 1975 By Derek Wood (Macdonald and Janes, London, 1976), £8.50, 357 pages Reviewed by W. Rusby. Rest in peace and war: Two Monsoons By Theon Wilkinson (Duckworth, London), £5.95, 240 pages Reviewed by Martin Lindsay. Rest in peace and war: Before Endeavours Fade: a Guide to the Battlefields of the First World War By Rose E. B. Coombs (Battle of Britain Prints International Ltd, London, 1976), £2.50, 136 pages Reviewed by James Marshall-Cornwall. [ABSTRACT FROM PUBLISHER]

This article examines the operational research conducted by the counter-battery staff office (CBO) in the headquarters of the Canadian Corps during the First World War. It challenges the argument presented by most historians of operational research, who contend that the discipline originated with the 1935 Tizard Committee and came to fruition during the Second World War and expands upon the initial inquiry performed by scholars J.S. Finan and W.J. Hurley in a 1997 journal article. While the staff of the CBO never used the term "operational research" to describe their scientific studies, they were undoubtedly its practitioners through their innovating, trialling, experimentation and dissemination of knowledge-the four pillars of the discipline. These artillerymen applied science to their weapon systems and, in doing so, made them as efficient and effective as possible. And they shared best practices with other formations in the British Expeditionary Force. Through their studies, the Canadian Corps perfected the use of counter-battery fire to attrit the German Army and strike their most important systems. Several of the studies conducted by these staff officers were mirrored by investigations carried out by No. 2 Operational Research Section during the Second World War. As a result, this study offers a new interpretation of adaptation to technology, scientific approach to operations and learning within the Canadian Corps during the First World War. [ABSTRACT FROM AUTHOR]

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophrenia or schizoaffective disorder (fBIRN Data Repository and the Consortium for Neuropsychiatric Phenomics), as well as 636 first-episode psychosis (FEP) participants from the Prevention and Early Intervention Program for Psychosis (PEPP-Montreal). In all participants, the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were collected. Multidimensional scaling (MDS) combined with cluster analysis was applied to SAPS and SANS scores across these two groups of participants. MDS revealed relationships between items of SAPS and SANS. Our application of cluster analysis to these results identified: 1 cluster of disorganization symptoms, 2 clusters of hallucinations/delusions, and 2 SANS clusters (asocial and apathy, speech and affect). Those reality distortion items which were furthest from auditory hallucinations had very weak to no relationship with hallucination severity. Despite being at an earlier stage of illness, symptoms in FEP presentations were similarly organized. While hallucinations and delusions commonly co-occur, we found that their specific themes and content sometimes travel together and sometimes do not. This has important implications, not only for treatment, but also for research—particularly efforts to understand the neurocomputational and pathophysiological mechanism underlying delusions and hallucinations. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Active inference has become an influential concept in psychopathology. We apply active inference to investigate conceptual disorganization in first-episode schizophrenia. We conceptualize speech production as a decision-making process affected by the latent "conceptual organization"—as a special case of uncertainty about the causes of sensory information. Uncertainty is both minimized via speech production—in which function words index conceptual organization in terms of analytic thinking—and tracked by a domain-general salience network. We hypothesize that analytic thinking depends on conceptual organization. Therefore, conceptual disorganization in schizophrenia would be both indexed by low conceptual organization and reflected in the effective connectivity within the salience network. Study Design With 1-minute speech samples from a picture description task and resting state fMRI from 30 patients and 30 healthy subjects, we employed dynamic causal and probabilistic graphical models to investigate if the effective connectivity of the salience network underwrites conceptual organization. Study Results Low analytic thinking scores index low conceptual organization which affects diagnostic status. The influence of the anterior insula on the anterior cingulate cortex and the self-inhibition within the anterior cingulate cortex are elevated given low conceptual organization (ie, conceptual disorganization). Conclusions Conceptual organization, a construct that explains formal thought disorder, can be modeled in an active inference framework and studied in relation to putative neural substrates of disrupted language in schizophrenia. This provides a critical advance to move away from rating-scale scores to deeper constructs in the pursuit of the pathophysiology of formal thought disorder. [ABSTRACT FROM AUTHOR]