Disturbing visual working memory:electrophysiological evidence for a role of the prefrontal cortex in recovery from interference

Single cell recordings in monkeys support the notion that the lateral prefrontal cortex (PFC) controls reactivation of visual working memory representations when rehearsal is disrupted. In contrast, recent fMRI findings yielded a double dissociation for PFC and the medial temporal lobe (MTL) in a letter working memory task. PFC was engaged in interference protection during reactivation while MTL was prominently involved in the retrieval of the letter representations. We present event-related potential data (ERP) that support PFC involvement in the top-down control of reactivation during a visual working memory task with endogenously triggered recovery after visual interference. A differentiating view is proposed for the role of PFC in working memory with respect to endogenous/exogenous control and to stimulus type. General implications for binding and retention mechanisms are discussed.

The functional neuroanatomy of auditory sensory gating and its behavioural implications

Auditory sensory gating (ASG) is the ability in individuals to suppress incoming irrelevant sensory input, indexed by evoked response to paired auditory stimuli. ASG is impaired in psychopathology such as schizophrenia, in which it has been proposed as putative endophenotype. This study aims to characterise electrophysiological properties of the phenomenon using MEG in time and frequency domains as well as to localise putative networks involved in the process at both sensor and source level. We also investigated the relationship between ASG measures and personality profiles in healthy participants in the light of its candidate endophenotype role in psychiatric disorders. Auditory evoked magnetic fields were recorded in twenty seven healthy participants by P50 ‘paired-click’ paradigm presented in pairs (conditioning stimulus S1- testing stimulus S2) at 80dB, separated by 250msec with inter trial interval of 7-10 seconds. Gating ratio in healthy adults ranged from 0.5 to 0.8 suggesting dimensional nature of P50 ASG. The brain regions active during this process were bilateral superior temporal gyrus (STG) and bilateral inferior frontal gyrus (IFG); activation was significantly stronger in IFG during S2 as compared to S1 (at p<0.05). Measures of effective connectivity between these regions using DCM modelling revealed the role of frontal cortex in modulating ASG as suggested by intracranial studies, indicating major role of inhibitory interneuron connections. Findings from this study identified a unique event-related oscillatory pattern for P50 ASG with alpha (STG)-beta (IFG) desynchronization and increase in cortical oscillatory gamma power (IFG) during S2 condition as compared to S1. These findings show that the main generator for P50 response is within temporal lobe and that inhibitory interneurons and gamma oscillations in the frontal cortex contributes substantially towards sensory gating. Our findings also show that ASG is a predictor of personality profiles (introvert vs extrovert dimension).

Coping with life events through possible selves

This study examines the integration of life events into the possible selves repertoire and explores the potential relationship between event-related possible selves and coping. The sample consisted of 198 participants, with age ranging from 18 - 84. Participants were administered interviews consisting of demographic information, the Possible Selves Interview, the Social Readjustment Rating Scale, the Ways of Coping Checklist-Revised, the Satisfaction with Life Scale, and the General Well-Being Schedule. Results indicate that the Integration of stressful events into the possible selves repertoire positively impacted coping. This study paves the way for important prevention programs aimed at promoting an individual's well being.

Expert players accurately detect an opponent's movement intentions through sound alone

Sounds offer a rich source of information about events taking place in our physical and social environment. However, outside the domains of speech and music, little is known about whether humans can recognize and act upon the intentions of another agent’s actions detected through auditory information alone. In this study we assessed whether intention can be inferred from the sound an action makes, and in turn, whether this information can be used to prospectively guide movement. In two experiments experienced and novice basketball players had to virtually intercept an attacker by listening to audio recordings of that player’s movements. In the first experiment participants had to move a slider, while in the second one their body, to block the perceived passage of the attacker as they would in a real basketball game. Combinations of deceptive and non-deceptive movements were used to see if novice and/or experienced listeners could perceive the attacker’s intentions through sound alone. We showed that basketball players were able to more accurately predict final running direction compared to non-players, particularly in the second experiment when the interceptive action was more basketball specific. We suggest that athletes present better action anticipation by being able to pick up and use the relevant kinematic features of deceptive movement from event-related sounds alone. This result suggests that action intention can be perceived through the sound a movement makes and that the ability to determine another person’s action intention from the information conveyed through sound is honed through practice.

Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU):A randomised, double-blind, placebo-controlled trial

Background: Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes. Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness. The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma. Methods: We did this double-blind, placebo-controlled randomised trial in a general adult intensive care unit (ICU). Critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission were enrolled. Patients were randomised (by an independent nurse, in 1:1 ratio, with permuted block size of four and six, using a centralised, secure web-based randomisation service) to receive haloperidol 2·5 mg or 0·9% saline placebo intravenously every 8 h, irrespective of coma or delirium status. Study drug was discontinued on ICU discharge, once delirium-free and coma-free for 2 consecutive days, or after a maximum of 14 days of treatment, whichever came first. Delirium was assessed using the confusion assessment method for the ICU (CAM-ICU). The primary outcome was delirium-free and coma-free days, defined as the number of days in the first 14 days after randomisation during which the patient was alive without delirium and not in coma from any cause. Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma. ICU clinical and research staff and patients were masked to treatment throughout the study. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN83567338. Findings: 142 patients were randomised, 141 were included in the final analysis (71 haloperidol, 70 placebo). Patients in the haloperidol group spent about the same number of days alive, without delirium, and without coma as did patients in the placebo group (median 5 days [IQR 0-10] vs 6 days [0-11] days; p=0·53). The most common adverse events were oversedation (11 patients in the haloperidol group vs six in the placebo group) and QTc prolongation (seven patients in the haloperidol group vs six in the placebo group). No patient had a serious adverse event related to the study drug. Interpretation: These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients. Although haloperidol can be used safely in this population of patients, pending the results of trials in progress, the use of intravenous haloperidol should be reserved for short-term management of acute agitation. Funding: National Institute for Health Research. © 2013 Elsevier Ltd.

Social Influences of Error Monitoring

Adolescence is characterized by dramatic hormonal, physical, and psychological changes, and is a period of risk for affective and anxiety disorders. Pubertal development during adolescence plays a major role in the emergence of these disorders, particularly among girls. Thus, it is critical to identify early biomarkers of risk. One potential biomarker, the error-related negativity (ERN), is an event-related potential following an erroneous response. Individuals with an anxiety disorder demonstrate a greater ERN than healthy comparisons, an association which is stronger in adolescence, suggesting that pubertal development may play a role in the ERN as a predictor of anxiety. One form of anxiety often observed in adolescence, particularly among girls, is social anxiety, which is defined as anxiety elicited by social-evaluative contexts. In adults, enhancements of the ERN in social-evaluative contexts is positively related to social anxiety symptoms, suggesting that the ERN in social contexts may serve as a biomarker for social anxiety. This dissertation examined the ERN in and its relation with puberty and social anxiety among 76 adolescent girls. Adolescent girls completed a flanker task in two different

Parsing, Generation and Grammar

Humans use their grammatical knowledge in more than one way. On one hand, they use it to understand what others say. On the other hand, they use it to say what they want to convey to others (or to themselves). In either case, they need to assemble the structure of sentences in a systematic fashion, in accordance with the grammar of their language. Despite the fact that the structures that comprehenders and speakers assemble are systematic in an identical fashion (i.e., obey the same grammatical constraints), the two ‘modes’ of assembling sentence structures might or might not be performed by the same cognitive mechanisms. Currently, the field of psycholinguistics implicitly adopts the position that they are supported by different cognitive mechanisms, as evident from the fact that most psycholinguistic models seek to explain either comprehension or production phenomena. The potential existence of two independent cognitive systems underlying linguistic performance doubles the problem of linking the theory of linguistic knowledge and the theory of linguistic performance, making the integration of linguistics and psycholinguistic harder. This thesis thus aims to unify the structure building system in comprehension, i.e., parser, and the structure building system in production, i.e., generator, into one, so that the linking theory between knowledge and performance can also be unified into one. I will discuss and unify both existing and new data pertaining to how structures are assembled in understanding and speaking, and attempt to show that the unification between parsing and generation is at least a plausible research enterprise. In Chapter 1, I will discuss the previous and current views on how parsing and generation are related to each other. I will outline the challenges for the current view that the parser and the generator are the same cognitive mechanism. This single system view is discussed and evaluated in the rest of the chapters. In Chapter 2, I will present new experimental evidence suggesting that the grain size of the pre-compiled structural units (henceforth simply structural units) is rather small, contrary to some models of sentence production. In particular, I will show that the internal structure of the verb phrase in a ditransitive sentence (e.g., The chef is donating the book to the monk) is not specified at the onset of speech, but is specified before the first internal argument (the book) needs to be uttered. I will also show that this timing of structural processes with respect to the verb phrase structure is earlier than the lexical processes of verb internal arguments. These two results in concert show that the size of structure building units in sentence production is rather small, contrary to some models of sentence production, yet structural processes still precede lexical processes. I argue that this view of generation resembles the widely accepted model of parsing that utilizes both top-down and bottom-up structure building procedures. In Chapter 3, I will present new experimental evidence suggesting that the structural representation strongly constrains the subsequent lexical processes. In particular, I will show that conceptually similar lexical items interfere with each other only when they share the same syntactic category in sentence production. The mechanism that I call syntactic gating, will be proposed, and this mechanism characterizes how the structural and lexical processes interact in generation. I will present two Event Related Potential (ERP) experiments that show that the lexical retrieval in (predictive) comprehension is also constrained by syntactic categories. I will argue that the syntactic gating mechanism is operative both in parsing and generation, and that the interaction between structural and lexical processes in both parsing and generation can be characterized in the same fashion. In Chapter 4, I will present a series of experiments examining the timing at which verbs’ lexical representations are planned in sentence production. It will be shown that verbs are planned before the articulation of their internal arguments, regardless of the target language (Japanese or English) and regardless of the sentence type (active object-initial sentence in Japanese, passive sentences in English, and unaccusative sentences in English). I will discuss how this result sheds light on the notion of incrementality in generation. In Chapter 5, I will synthesize the experimental findings presented in this thesis and in previous research to address the challenges to the single system view I outlined in Chapter 1. I will then conclude by presenting a preliminary single system model that can potentially capture both the key sentence comprehension and sentence production data without assuming distinct mechanisms for each.

Effetto di distrattori acustici rispetto a distrattori visivi in un compito di memoria visiva: analisi del segnale EEG

Studi recenti hanno evidenziato cambiamenti nei ritmi alpha (8-12 Hz) e theta (4-8 Hz) in vari processi modulatori top-down e di controllo cognitivo come la memoria di lavoro (WM, working memory) e la soppressione di distrattori. I compiti di WM richiedono attenzione interna sostenuta per dare priorità alle informazioni rilevanti a discapito di quelle interferenti che distraggono dall’obiettivo. I meccanismi di attenzione in tali compiti sono associati ad aumento di potenza alpha, che riflette la funzione inibitoria di tale ritmo, in regioni che elaborano informazioni distraenti, e ad aumento di potenza theta, soprattutto in regioni frontali, che riflette funzioni di controllo cognitivo per raggiungere l’obiettivo pur in presenza di interferenze. Questo lavoro è volto ad indagare gli effetti di distrattori acustici rispetto a distrattori visivi in un compito di visual WM. A tale scopo sono stati acquisiti ed elaborati i segnali EEG di 12 soggetti volontari mentre eseguivano un compito di visual WM, in cui la fase di retention (mantenimento in memoria delle informazioni codificate) veniva interrotta con la presentazione di distrattori di due modalità sensoriali differenti (visiva e acustica), per valutare le variazioni dell’attività cerebrale in termini di ritmi alpha e theta e le regioni coinvolte. Si è osservato un aumento maggiore di potenza alpha (principalmente posteriore) in presenza del distrattore acustico rispetto al visivo sia nella fase pre-distrattore che nella fase distrattore, statisticamente significativo nella fase distrattore. Si è osservato un aumento maggiore di potenza theta (principalmente frontale) in presenza del distrattore acustico rispetto al visivo in tutte le fasi del task, statisticamente significativo nella fase iniziale di retention e nella fase del distrattore. I risultati potrebbero indicare una maggiore necessità di controllo cognitivo e di protezione da stimoli interferenti in caso di distrattore acustico rispetto al visivo.

Age-related changes in ERPs associated with context-based and response-based interference

Age-related differences in information processing have often been explained through deficits in older adults' ability to ignore irrelevant stimuli and suppress inappropriate responses through inhibitory control processes. Functional imaging work on young adults by Nelson and colleagues (2003) has indicated that inferior frontal and anterior cingulate cortex playa key role in resolving interference effects during a delay-to-match memory task. Specifically, inferior frontal cortex appeared to be recruited under conditions of context interference while the anterior cingulate was associated with interference resolution at the stage of response selection. Related work has shown that specific neural activities related to interference resolution are not preserved in older adults, supporting the notion of age-related declines in inhibitory control (Jonides et aI., 2000, West et aI., 2004b). In this study the time course and nature of these inhibition-related processes were investigated in young and old adults using high-density ERPs collected during a modified Sternberg task. Participants were presented with four target letters followed by a probe that either did or did not match one of the target letters held in working memory. Inhibitory processes were evoked by manipulating the nature of cognitive conflict in a particular trial. Conflict in working memory was elicited through the presentation of a probe letter in immediately previous target sets. Response-based conflict was produced by presenting a negative probe that had just been viewed as a positive probe on the previous trial. Younger adults displayed a larger orienting response (P3a and P3b) to positive probes relative to a non-target baseline. Older adults produced the orienting P3a and 3 P3b waveforms but their responses did not differentiate between target and non-target stimuli. This age-related change in response to targetness is discussed in terms of "early selection/late correction" models of cognitive ageing. Younger adults also showed a sensitivity in their N450 response to different levels of interference. Source analysis of the N450 responses to the conflict trials of younger adults indicated an initial dipole in inferior frontal cortex and a subsequent dipole in anterior cingulate cortex, suggesting that inferior prefrontal regions may recruit the anterior cingulate to exert cognitive control functions. Individual older adults did show some evidence of an N450 response to conflict; however, this response was attenuated by a co-occurring positive deflection in the N450 time window. It is suggested that this positivity may reflect a form of compensatory activity in older adults to adapt to their decline in inhibitory control.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

A synchronous, middle early Aptian age for the demise of the Helvetic Urgonian platform related to the unfolding oceanic anoxic event 1a ("Selli event")

Un âge synchrone (partie moyenne de l'Aptien inférieur) de l'ennoiement de la plate-forme Urgonienne helvétique en relation avec l'événement océanique anoxique 1a ("événement Selli"). - La fin de la plate-forme urgonienne, calibrée par analyse des isotopes stables du carbone sur roche totale et par biostratigraphie basée sur les ammonites, est datée du milieu de l'Aptien inférieur (Près de la limite des zones weissi et deshayesi). Cet arrêt, synchrone dans des coupes représentatives du domaine helvétique alpin, est un événement environemental majeur renregistré en France, en Espagne, au Protugal, en Oman, au Mexique et dans le domaine Pacifique. En tenant compte des limites de résolution de la biostatrigraphie et des autres techniques de datation, cet épisode semble également être synchrone à l'échelle globale. Pour beaucoup d'auteurs, la disparition de récifs de coraux et de rudistes corrélée à la fin de la sédimentation urgonienne correspond à la mise en place de conditions anoxiques à l'Aptien inférieur. Celles-ci caractérisent un événement d'importance global: l'événement anoxique OAE 1a.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Global warming potentials and radiative efficiencies of halocarbons and related compounds: a comprehensive review

In the mid-1970s it was recognized that, as well as being substances that deplete stratospheric ozone, chlorofluorocarbons (CFCs) were strong greenhouse gases that could have substantial impacts on radiative forcing of climate change. Around a decade later, this group of radiatively active compounds was expanded to include a large number of replacements for ozone-depleting substances such as chlorocarbons, hydrochlorocarbons, hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), bromofluorocarbons, and bromochlorofluorocarbons. This paper systematically reviews the published literature concerning the radiative efficiencies (REs) of CFCs, bromofluorocarbons and bromochlorofluorocarbons (halons), HCFCs, HFCs, PFCs, SF6, NF3, and related halogen containing compounds. In addition we provide a comprehensive and self-consistent set of new calculations of REs and global warming potentials (GWPs) for these compounds, mostly employing atmospheric lifetimes taken from the available literature. We also present Global Temperature change Potentials (GTPs) for selected gases. Infrared absorption spectra used in the RE calculations were taken from databases and individual studies, and from experimental and ab initio computational studies. Evaluations of REs and GWPs are presented for more than 200 compounds. Our calculations yield REs significantly (> 5%) different from those in the Intergovernmental Panel on Climate Change Fourth Assessment Report (AR4) for 49 compounds. We present new RE values for more than 100 gases which were not included in AR4. A widely-used simple method to calculate REs and GWPs from absorption spectra and atmospheric lifetimes is assessed and updated. This is the most comprehensive review of the radiative efficiencies and global warming potentials of halogenated compounds performed to date.