Explore the vast range of titles available.

It has been proposed that people employ a common set of sustained operations (retrieval mode) when preparing to remember different kinds of episodic information. In two experiments, however, there was no evidence for the pattern of brain activity commonly assumed to index these operations. In both experiments event-related potentials (ERPs) were recorded time-locked to alternating preparatory cues signalling that participants should prepare for different retrieval tasks. One cue signalled episodic retrieval: remember the location where the object was presented in a prior study phase. The other signalled semantic retrieval: identify the location where the object is most commonly found (Experiment 1) or identify the typical size of the object (Experiment 2). In both experiments, only two trials of the same task were completed in succession. This enabled ERP contrasts between 'repeat' trials (the cue on the preceding trial signalled the same retrieval task), and 'switch' trials (the cue differed from the preceding trial). There were differences between the ERPs elicited by the preparatory task cues in Experiment 1 only: these were evident only on switch trials and comprised more positive-going activity over right-frontal scalp for the semantic than for the episodic task. These findings diverge from previous outcomes where the activity differentiating cues signalling preparation for episodic or semantic retrieval has been restricted to right-frontal scalp sites, comprising more positive-going activity for the episodic than for the semantic task. While these findings are consistent with the view that there is not a common set of operations engaged when people prepare to remember different kinds of episodic information, an alternative account is offered here, which is that these outcomes are a consequence of structural and temporal components of the experiment designs.

To remember information from our personal past we need to be in a cognitive state where we treat stimuli as cues for memory retrieval. In this study we considered whether participants could exert control and disengage from a memory state when it was no longer required for the task at hand. In particular, we examined whether this ability was affected by the valence of the stimuli and participant’s rumination scores. After a study phase participants completed test blocks where the task switched every two trials between a memory task (retrieving information from the study phase) and a perceptual task. Even though there was no episodic memory requirement in the perceptual task, a well-established event-related potential (ERP) index of memory retrieval was present for both trials when the stimuli were negative valenced pictures but not for neutral pictures. Furthermore, there was a positive correlation between the magnitude of this ERP memory index in the perceptual task and rumination scores but only for neutral stimuli and not negative. Thus, in this study participants generally had difficultly suppressing memory retrieval when negative stimuli were presented. However, for neutral stimuli only ruminators were more susceptible to memory intrusions.

Neural activity preceding memory probes differs according to retrieval goals. These divergences have been linked to retrieval orientations, which are content-specific memory states that bias retrieval towards specific contents. Here, participants were cued to retrieve either spatial location or encoding operations. On the first trial of each memory task (‘switch’ trials), preparatory ERPs preceding correct source memory judgments differed according to retrieval goal, but this effect was absent preceding memory errors. Initiating appropriate retrieval orientations therefore predicted criterial recollection. Preparatory ERPs on the second trial of each memory task (i.e. ‘stay’ trials) also differed according to retrieval goal, but the polarity of this effect was reversed from that observed on switch trials and the effect did not predict memory accuracy. This was interpreted as a correlate of retrieval orientation maintenance, with initiation and maintenance forming dissociable components of these goal-directed memory states. More generally, these findings highlight the importance of pre-retrieval processes in episodic memory. [Display omitted] •Pre-retrieval ERPs diverged according to cues signalling two different episodic tasks.•This index predicted memory accuracy on the first trial of each task.•The initiation of task-specific retrieval orientations influences criterial recollection.•An orientation effect of reversed polarity on subsequent trials was linked with maintenance.•All pre-retrieval ERP effects were maximal at frontal electrode sites.

Both amplitude and latency of single-trial EEG/MEG recordings provide valuable information regarding functionality of the human brain. In this article, we provided a data-driven graph and network-based framework for mining information from multi-trial event-related brain recordings. In the first part, we provide the general outline of the proposed methodological approach. In the second part, we provide a more detailed illustration, and present the obtained results on every step of the algorithmic procedure. To justify the proposed framework instead of presenting the analytic data mining and graph-based steps, we address the problem of response variability, a prerequisite to reliable estimates for both the amplitude and latency on specific N/P components linked to the nature of the stimuli. The major question addressed in this study is the selection of representative single-trials with the aim of uncovering a less noisey averaged waveform elicited from the stimuli. This graph and network-based algorithmic procedure increases the signal-to-noise (SNR) of the brain response, a key pre-processing step to reveal significant and reliable amplitude and latency at a specific time after the onset of the stimulus and with the right polarity (N or P). We demonstrated the whole approach using electroencephalography (EEG) auditory mismatch negativity (MMN) recordings from 42 young healthy controls. The method is novel, fast and data-driven succeeding first to reveal the true waveform elicited by MMN on different conditions (frequency, intensity, duration, etc.). The proposed graph-oriented algorithmic pipeline increased the SNR of the characteristic waveforms and the reliability of amplitude and latency within the adopted cohort. We also demonstrated how different EEG reference schemes (REST vs. average) can influence amplitude-latency estimation. Simulation results revealed robust amplitude-latency estimations under different SNR and amplitude-latency variations with the proposed algorithm.

Background People with temporal lobe epilepsy (TLE) report significant problems with learning and memory. There are no effective therapies for combatting these problems in people with TLE, resulting in an unmet therapeutic need. The lack of treatment is, in part, due to a poor understanding of the neurobiology underlying these memory deficits. We know that hippocampal neurogenesis, a process believed to be important in learning and memory formation, is permanently reduced in chronic TLE, and this may go some way to explain the learning and memory impairments seen in people with TLE. The common anti-depressant drug fluoxetine has been shown to stimulate neurogenesis both in the healthy brain and in neurological diseases where neurogenesis is impaired. In an animal model of TLE, administration of fluoxetine was found to restore neurogenesis and improve learning on a complex spatial navigational task. We now want to test this effect in humans by investigating whether administration of fluoxetine to people with TLE can improve learning and memory. Methods This is a single-centre randomised controlled, double-blind feasibility trial. We plan to recruit 20 participants with a diagnosis of TLE and uni-lateral hippocampal sclerosis, confirmed by 3T MRI. Eligible participants will undergo baseline assessments of learning and memory prior to being randomised to either 20 mg/day fluoxetine or matching placebo for 60 days. Follow-up assessments will be conducted after 60 days of trial medication and then again at 60 days after cessation of trial medication. Feasibility will be assessed on measures of recruitment, retention and adherence against pre-determined criteria. Discussion This trial is designed to determine the feasibility of conducting a double-blind randomised controlled trial of fluoxetine for the treatment of learning and memory impairments in people with TLE. Data collected in this trial will inform the design and utility of any future efficacy trial involving fluoxetine for the treatment of learning and memory in people with TLE. Trial registration EudraCT 2014-005088-34 , registered on May 18, 2015

A widely held assumption is that memory retrieval is aided by cognitive control processes that are engaged flexibly in service of memory retrieval and memory decisions. While there is some empirical support for this view, a notable exception is the absence of evidence for the flexible use of retrieval control in functional neuroimaging experiments requiring frequent switches between tasks with different cognitive demands. This absence is troublesome in so far as frequent switches between tasks mimic some of the challenges that are typically placed on memory outside the laboratory. In this experiment we instructed participants to alternate frequently between three episodic memory tasks requiring item recognition or retrieval of one of two different kinds of contextual information encoded in a prior study phase (screen location or encoding task). Event-related potentials (ERPs) elicited by unstudied items in the two tasks requiring retrieval of study context were reliably different, demonstrating for the first time that ERPs index task-specific processing of retrieval cues when retrieval goals change frequently. The inclusion of the item recognition task was a novel and important addition in this study, because only the ERPs elicited by unstudied items in one of the two context conditions diverged from those in the item recognition condition. This outcome constrains functional interpretations of the differences that emerged between the two context conditions and emphasises the utility of this baseline in functional imaging studies of retrieval processing operations. [Display omitted] •Three different episodic memory tasks were intermixed.•Event-related potential correlates of unstudied retrieval cues were analysed by task.•Neural correlates of these items differed according to retrieval task.•Novel ERP evidence for flexible task-dependent processing of retrieval cues.

One influential explanation for the costs incurred when switching between tasks is that they reflect interference arising from completing the previous task—known as task-set inertia. We report a novel approach for assessing task-set inertia in a memory experiment using event-related potentials (ERPs). After a study phase, participants completed a test block in which they switched between a memory task (retrieving information from the study phase) and a perceptual task. These tasks alternated every two trials. An ERP index of the retrieval of study information was evident in the memory task. It was also present on the first trial of the perceptual task but was markedly attenuated on the second. Moreover, this task-irrelevant ERP activity was positively correlated with a behavioral cost associated with switching between tasks. This real-time measure of neural activity thus provides direct evidence of task-set inertia, its duration, and the functional role it plays in switch costs.

It has been suggested that retrieving episodic information can involve adopting a cognitive state or set: retrieval mode. In a series of studies, an event-related potential (ERP) index of retrieval mode has been identified in designs which cue participants on a trial-by-trial basis to switch between preparing for and then completing an episodic or non-episodic retrieval task. However, a confound in these studies is that along with task type the content of what is to be retrieved has varied. Here we examined whether the ERP index of retrieval mode remains when the contents of an episodic and non-episodic task are highly similar – both requiring a location judgement. In the episodic task participants indicated the screen location where words had been shown in a prior study phase (left/right/new); whereas in the perceptual task they indicated the current screen location of the word (top/middle/bottom). Consistent with previous studies the ERPs elicited while participants prepared for episodic retrieval were more positive-going at right-frontal sites than when they prepared for the perceptual task. This index was observed, however, on the first trial after participants had switched tasks, rather than on the second trial, as has been observed previously. Potential reasons for this are discussed, including the critical manipulation of similarity in contents between tasks, as well as the use of a predictable cue sequence. •People were cued to switch between episodic and non-episodic cognitive tasks.•Both tasks required judgements about stimulus location.•ERPs were acquired in response to the cues signalling which task to complete.•Preparatory ERPs for episodic retrieval had different timings than in prior studies.•These outcomes offer new insights into processes that facilitate episodic retrieval.

Choosing between equally valued options can be a conundrum, for which classical decision theories predicted a prolonged response time (RT). Paradoxically, a rational decision-maker would need no deliberative thinking in this scenario, as outcomes of alternatives are indifferent. How individuals choose between equal options remain unclear. Here, we characterized the neurocognitive processes underlying such voluntary decisions, by integrating advanced cognitive modelling and EEG recording in a probabilistic reward task, in which human participants chose between pairs of cues associated with identical reward probabilities at different levels. We showed that higher reward certainty accelerated RT. At each certainty level, participants preferred to choose one cue faster and more frequently over the other. The behavioral effects on RT persisted in simple reactions to reward cues. By using hierarchical Bayesian parameter estimation for an accumulator model, we showed that the certainty and preference effects were independently associated with the rate of evidence accumulation during decisions, but not with visual encoding or motor execution latencies. Time-resolved multivariate pattern classification of EEG evoked response identified significant representations of reward certainty and preference choices as early as 120 ms after stimulus onset, with spatial relevance patterns maximal in middle central and parietal electrodes. Furthermore, EEG-informed computational modelling showed that the rate of change between N100 and P300 event-related potentials reflected changes in the model-derived rate of evidence accumulation on a trial-by-trial basis. Our findings suggested that reward certainty and preference collectively shaped voluntary decisions between equal options, providing a mechanism to prevent indecision or random behavior.

Context. —There is increasing interest in using whole slide imaging (WSI) for diagnostic purposes (primary and/or consultation). An important consideration is whether WSI can safely replace conventional light microscopy as the method by which pathologists review histologic sections, cytology slides, and/or hematology slides to render diagnoses. Validation of WSI is crucial to ensure that diagnostic performance based on digitized slides is at least equivalent to that of glass slides and light microscopy. Currently, there are no standard guidelines regarding validation of WSI for diagnostic use. Objective. —To recommend validation requirements for WSI systems to be used for diagnostic purposes. Design. —The College of American Pathologists Pathology and Laboratory Quality Center convened a nonvendor panel from North America with expertise in digital pathology to develop these validation recommendations. A literature review was performed in which 767 international publications that met search term requirements were identified. Studies outside the scope of this effort and those related solely to technical elements, education, and image analysis were excluded. A total of 27 publications were graded and underwent data extraction for evidence evaluation. Recommendations were derived from the strength of evidence determined from 23 of these published studies, open comment feedback, and expert panel consensus. Results. —Twelve guideline statements were established to help pathology laboratories validate their own WSI systems intended for clinical use. Validation of the entire WSI system, involving pathologists trained to use the system, should be performed in a manner that emulates the laboratory's actual clinical environment. It is recommended that such a validation study include at least 60 routine cases per application, comparing intraobserver diagnostic concordance between digitized and glass slides viewed at least 2 weeks apart. It is important that the validation process confirm that all material present on a glass slide to be scanned is included in the digital image. Conclusions. —Validation should demonstrate that the WSI system under review produces acceptable digital slides for diagnostic interpretation. The intention of validating WSI systems is to permit the clinical use of this technology in a manner that does not compromise patient care.