Misattribution, false recognition and the sins of memory

Memory is sometimes a troublemaker. Schacter has classified memory's transgressions into seven fundamental 'sins': transience, absent-mindedness, blocking, misattribution, suggestibility, bias and persistence. This paper focuses on one memory sin, misattribution, that is implicated in false or illusory recognition of episodes that never occurred. We present data from cognitive, neuropsychological and neuroimaging studies that illuminate aspects of misattribution and false recognition. We first discuss cognitive research examining possible mechanisms of misattribution associated with false recognition. We also consider ways in which false recognition can be reduced or avoided, focusing in particular on the role of distinctive information. We next turn to neuropsychological research concerning patients with amnesia and Alzheimer's disease that reveals conditions under which such patients are less susceptible to false recognition than are healthy controls, thus providing clues about the brain mechanisms that drive false recognition. We then consider neuroimaging studies concerned with the neural correlates of true and false recognition, examining when the two forms of recognition can and cannot be distinguished on the basis of brain activity. Finally, we argue that even though misattribution and other memory sins are annoying and even dangerous, they can also be viewed as by-products of adaptive features of memory.     

A new penumbra: transitioning from injury into repair after stroke

The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and metabolism. The second decade advanced our understanding of molecular mechanisms that mediate penumbral cell death. And the third decade saw the rapid development of clinical neuroimaging tools that are now increasingly applied in stroke patients. But how can we look ahead as we move into the fourth decade of penumbra research? This author speculates that a paradigm shift is needed. Most molecular targets for therapy have biphasic roles in stroke pathophysiology. During the acute phase, these targets mediate injury. During the recovery phase, the same mediators contribute to neurovascular remodeling. It is this boundary zone that comprises the new penumbra, and future investigations should dissect where, when and how damaged brain makes the transition from injury into repair.     

Electroencephalographic imaging of higher brain function.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.     

The effects of visual object priming on brain activation before and after recognition

BACKGROUND: Recognizing an object is improved by recent experience with that object even if one cannot recall seeing the object. This perceptual facilitation as a result of previous experience is called priming. In neuroimaging studies, priming is often associated with a decrease in activation in brain regions involved in object recognition. It is thought that this occurs because priming causes a sharpening of object representations which leads to more efficient processing and, consequently, a reduction in neural activity. Recent evidence has suggested, however, that the apparent effect of priming on brain activation may vary as a function of whether the neural activity is measured before or after recognition has taken place. RESULTS: Using a gradual 'unmasking' technique, we presented primed and non-primed objects to subjects, and measured activation time courses using high-field functional magnetic resonance imaging (fMRI). As the objects were slowly revealed, but before recognition had occurred, activation increased from baseline level to a peak that corresponded in time to the subjects' behavioural recognition responses. The activation peak for primed objects occurred sooner than the peak for non-primed objects, and subjects responded sooner when presented with a primed object than with a non-primed object. During this pre-recognition phase, primed objects produced more activation than non-primed objects. After recognition, activation declined rapidly for both primed and non-primed objects, but now activation was lower for the primed objects. CONCLUSIONS: Priming did not produce a general decrease in activation in the brain regions involved in object recognition but, instead, produced a shift in the time of peak activation that corresponded to the shift in time seen in the subjects' behavioural recognition performance.     

L’apport de la neuro-imagerie dans la maladie d’Alzheimer

Today, the role of neuroimaging in the diagnosis of Alzheimer’s disease (AD) extends beyond its traditional role of excluding other conditions such as neurosurgical lesions. Modern challenges for neuroimaging techniques aim to contribute to the early diagnosis of AD. Early diagnosis includes recognition of pre-demented conditions, such as people with mild cognitive impairment (MCI) or with high risk of developing AD. In addition, early diagnosis would allow early treatment using currently available therapies or new therapies in the future. In this article, we will present the modern role of neuroimaging in AD. Structural MRI can detect and follow the time course of medial temporal lobe atrophy as a surrogate marker for the pathological process. New MRI techniques and image analysis software can detect subtle brain diffusion, perfusion or metabolic changes thus providing new tools for studying the pathological process. New ligands are also available for studies using tracers and positron emission tomography.     

Psychophysiology of false memories in a Deese-Roediger-McDermott paradigm with visual scenes

Remembering something that has not in fact been experienced is commonly referred to as false memory. The Deese-Roediger-McDermott (DRM) paradigm is a well-elaborated approach to this phenomenon. This study attempts to investigate the peripheral physiology of false memories induced in a visual DRM paradigm. The main research question is whether false recognition is different from true recognition in terms of accompanying physiological responses.Sixty subjects participated in the experiment, which included a study phase with visual scenes each showing a group of interrelated items in social contexts. Subjects were divided into an experimental group undergoing a classical DRM design and a control group without DRM manipulation. The control group was implemented in order to statistically control for possible biases produced by memorability differences between stimulus types. After a short retention interval, a pictorial recognition phase was conducted in the manner of a Concealed Information Test. Simultaneous recordings of electrodermal activity, respiration line length, phasic heart rate, and finger pulse waveform length were used. Results yielded a significant Group by Item Type interaction, showing that true recognition is accompanied by greater electrodermal activity than false recognition.Results are discussed in the light of Sokolov's Orienting Reflex, the Preliminary Process Theory and the Concealed Information Test. Implications and restrictions of the introduced design features are critically discussed. This study demonstrates the applicability of measures of peripheral physiology to the field of false memory research.     

Automated,High Accuracy Classification of Parkinsonian Disorders: A Pattern Recognition Approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process.     

High-resolution fMRI maps of cortical activation in nonhuman primates: correlation with intrinsic signal optical images

One of the most widely used functional brain mapping tools is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). This method has contributed to new understandings of the functional roles of different areas in the human brain. However, its ability to map cerebral cortex at high spatial (submillimeter) resolution is still unknown. Other methods such as single- and multiunit electrophysiology and intrinsic signal optical imaging have revealed submillimeter resolution of sensory topography and cortical columnar activations. However, they are limited either by spatial scale (electrophysiology characterizes only local groups of neurons) or by the inability to monitor deep structures in the brain (i.e., cortical regions buried in sulci or subcortical structures). A method that could monitor all regions of the brain at high spatial resolution would be ideal. This capacity would open the doors to investigating, for example, how networks of cerebral cortical columns relate to or produce behavior. In this article we demonstrate that, without benefit of contrast agents, at a magnetic field strength of 9.4 tesla, BOLD fMRI can reveal millimeter-sized topographic maps of digit representation in the somatosensory cortex of the anesthetized squirrel monkey. Furthermore, by mapping the "funneling illusion," it is possible to detect even submillimeter shifts in activation in the cortex. Our data suggest that at high magnetic field strength, the positive BOLD signal can be used to reveal high spatial resolution maps of brain activity, a finding that weakens previous notions about the ultimate spatial specificity of the positive BOLD signal.     

The Neural Basis of Testable and Non-Testable Beliefs

Beliefs about the state of the world are an important influence on both normal behavior and psychopathology. However, understanding of the neural basis of belief processing remains incomplete, and several aspects of belief processing have only recently been explored. Specifically, different types of beliefs may involve fundamentally different inferential processes and thus recruit distinct brain regions. Additionally, neural processing of truth and falsity may differ from processing of certainty and uncertainty. The purpose of this study was to investigate the neural underpinnings of assessment of testable and non-testable propositions in terms of truth or falsity and the level of certainty in a belief. Functional magnetic resonance imaging (fMRI) was used to study 14 adults while they rated propositions as true or false and also rated the level of certainty in their judgments. Each proposition was classified as testable or non-testable. Testable propositions activated the DLPFC and posterior cingulate cortex, while non-testable statements activated areas including inferior frontal gyrus, superior temporal gyrus, and an anterior region of the superior frontal gyrus. No areas were more active when a proposition was accepted, while the dorsal anterior cingulate was activated when a proposition was rejected. Regardless of whether a proposition was testable or not, certainty that the proposition was true or false activated a common network of regions including the medial prefrontal cortex, caudate, posterior cingulate, and a region of middle temporal gyrus near the temporo-parietal junction. Certainty in the truth or falsity of a non-testable proposition (a strong belief without empirical evidence) activated the insula. The results suggest that different brain regions contribute to the assessment of propositions based on the type of content, while a common network may mediate the influence of beliefs on motivation and behavior based on the level of certainty in the belief.     

What are the baselines for protein fold recognition?

MOTIVATION: What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein-ranging from the length of the sequence to a knowledge of its secondary structure-to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications? EXPERIMENTS PERFORMED: A number of rapid automatic methods which score similarities between protein domains were devised and tested. These methods ranged from those that incorporated no secondary structure information, such as measuring absolute differences in sequence lengths, to more complex alignments of secondary structure elements. Each method was assessed for accuracy by comparison with the Class Architecture Topology Homology (CATH) classification. Methods were rated against both a random baseline fold assignment method as a lower control and FSSP as an upper control. Similarity trees were constructed in order to evaluate the accuracy of optimum methods at producing a classification of structure. RESULTS: Using a rigorous comparison of methods with CATH, the random fold assignment method set a lower baseline of 11% true positives allowing for 3% false positives and FSSP set an upper benchmark of 47% true positives at 3% false positives. The optimum secondary structure alignment method used here achieved 27% true positives at 3% false positives. Using a less rigorous Critical Assessment of Structure Prediction (CASP)-like sensitivity measurement the random assignment achieved 6%, FSSP-59% and the optimum secondary structure alignment method-32%. Similarity trees produced by the optimum method illustrate that these methods cannot be used alone to produce a viable protein structural classification system. CONCLUSIONS: Simple methods that use perfect secondary structure information to assign folds cannot produce an accurate protein taxonomy, however they do provide useful baselines for fold recognition. In terms of a typical CASP assessment our results suggest that approximately 6% of targets with folds in the databases could be assigned correctly by randomly guessing, and as many as 32% could be recognised by trivial secondary structure comparison methods, given knowledge of their correct secondary structures.     

Rare variants in the splicing regulatory elements of EXOC3L4 are associated with brain glucose metabolism in Alzheimer’s disease

Background

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases that causes problems related to brain function. To some extent it is understood on a molecular level how AD arises, however there are a lack of biomarkers that can be used for early diagnosis. Two popular methods to identify AD-related biomarkers use genetics and neuroimaging. Genes and neuroimaging phenotypes have provided some insights as to the potential for AD biomarkers. While the field of imaging-genomics has identified genetic features associated with structural and functional neuroimaging phenotypes, it remains unclear how variants that affect splicing could be important for understanding the genetic etiology of AD.

Methods

In this study, rare variants (minor allele frequency?<?0.01) in splicing regulatory element (SRE) loci from whole genome sequencing (WGS) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, were used to identify genes that are associated with global brain cortical glucose metabolism in AD measured by FDG PET-scans. Gene-based associated analyses of rare variants were performed using the program BioBin and the optimal Sequence Kernel Association Test (SKAT-O).

Results

The gene, EXOC3L4, was identified as significantly associated with global cortical glucose metabolism (FDR (false discovery rate) corrected p?<?0.05) using SRE coding variants only. Three loci that may affect splicing within EXOC3L4 contribute to the association.

Conclusion

Based on sequence homology, EXOC3L4 is likely a part of the exocyst complex. Our results suggest the possibility that variants which affect proper splicing of EXOC3L4 via SREs may impact vesicle transport, giving rise to AD related phenotypes. Overall, by utilizing WGS and functional neuroimaging we have identified a gene significantly associated with an AD related endophenotype, potentially through a mechanism that involves splicing.

     

Neuroimaging studies of autobiographical event memory

Commonalities and differences in findings across neuroimaging studies of autobiographical event memory are reviewed. In general terms, the overall pattern across studies is of medial and left-lateralized activations associated with retrieval of autobiographical event memories. It seems that the medial frontal cortex and left hippocampus in particular are responsive to such memories. However, there are also inconsistencies across studies, for example in the activation of the hippocampus and dorsolateral prefrontal cortex. It is likely that methodological differences between studies contribute to the disparate findings. Quantifying and assessing autobiographical event memories presents a challenge in many domains, including neuroimaging. Methodological factors that may be pertinent to the interpretation of the neuroimaging data and the design of future experiments are discussed. Consideration is also given to aspects of memory that functional neuroimaging might be uniquely disposed to examine. These include assessing the functionality of damaged tissue in patients and the estimation of inter-regional communication (effective connectivity) between relevant brain regions.     

Lateral orbitofrontal cortex involvement in initial negative aesthetic impression formation

It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC) was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC.     

Neural Basis of Anticipatory Anxiety Reappraisals

Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging studies suggest that reappraisal recruits both medial and lateral prefrontal brain regions. However, few studies have investigated neural representation of reappraisals associated with anticipatory anxiety, and the specific nature of the brain activity underlying this process remains unclear. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with reappraisals of transient anticipatory anxiety. Although transient anxiety activated mainly subcortical regions, reappraisals targeting the anxiety were associated with increased activity in the medial and lateral prefrontal regions (including the orbitofrontal and anterior cingulate cortices). Reappraisal decreased fear circuit activity (including the amygdala and thalamus). Correlational analysis demonstrated that reductions in subjective anxiety associated with reappraisal were correlated with orbitofrontal and anterior cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal regions; particularly the orbitofrontal and anterior cingulate cortices are associated with successful use of this emotion regulation strategy.     

The neural structures expressing perceptual hysteresis in visual letter recognition

Perception can change nonlinearly with stimulus contrast, and perceptual threshold may depend on the direction of contrast change. Such hysteresis effects in neurometric functions provide a signature of perceptual awareness. We recorded brain activity with functional neuroimaging in observers exposed to gradual contrast changes of initially hidden visual stimuli. Lateral occipital, frontal, and parietal regions all displayed both transient activations and hysteresis that correlated with change and maintenance of a percept, respectively. Medial temporal activity did not follow perception but increased during hysteresis and showed transient deactivations during perceptual transitions. These findings identify a set of brain regions sensitive to visual awareness and suggest that medial temporal structures may provide backward signals that account for neural and, thereby, perceptual hysteresis.     

Neural mechanisms necessary for empathy-related phenomena across species

The neural basis of empathy and prosociality has received much interest over the past decades. Neuroimaging studies localized a network of brain regions with activity that correlates with empathy. Here, we review how the emergence of rodent and nonhuman primate models of empathy-related phenomena supplements human lesion and neuromodulation studies providing evidence that activity in several nodes is necessary for these phenomena to occur. We review proof that (i) affective states triggered by the emotions of others, (ii) motivations to act in ways that benefit others, and (iii) emotion recognition can be altered by perturbing brain activity in many nodes identified by human neuroimaging, with strongest evidence for the cingulate and the amygdala. We also include evidence that manipulations of the oxytocin system and analgesics can have such effects, the latter providing causal evidence for the recruitment of an individual's own nociceptive system to feel with the pain of others.     

Co-existence between the traditional societies and wildlife in western Serengeti, Tanzania: its relevancy in contemporary wildlife conservation efforts

This paper seeks to show how the traditional societies in western Serengeti have coexisted and continue to coexist with wildlife. It also recognizes the relevancy of this coexistence in furthering contemporary conservation efforts although there are practical constraints to putting this into practice. The following questions are examined: (1) How did/do traditional societies in Serengeti interact with their nature? (2) Which traditional management institutions governed/govern interaction between people and wildlife species, resources and ecosystems and, how do they operate? (3) Which factors were (or are) responsible for erosion of traditional management institutions? (4) What can the traditional practices offer to contemporary conservation efforts and what are the limitations? The paper identifies four ways in which traditional institutions and practices can contribute to current conservation efforts: regulating the overexploitation of resources; complementing the current incentives aiming at diffusing prevailing conflicts between conservation authorities and communities; minimising the costs of law enforcement and; complementing the modern scientific knowledge in monitoring and responding to ecosystem processes and functions. The practical constraints likely to limit adoption of these practices are presented as: methodological complications of acquiring indigenous knowledge; prevailing historical conflicts; human population growth; poverty and lack of appreciation among the conservation planners and managers. In conclusion the need to address the current constraints in order to achieve effective taping of the existing potentials is emphasized.     

Functional imaging of memory processes in humans: positron emission tomography and functional magnetic resonance imaging

Human memory is not a unitary function; it consists of multiple memory systems, with different characteristics and specialisations that are implemented in the brain. The cognitive neuroscience of human memory tries to comprehend how we encode, store, and retrieve memory items within and across those systems. The emergence of functional neuroimaging techniques offered the unprecedented opportunity to directly observe the brain regions engaged in memory functions. Brain imaging techniques can roughly be divided into those measuring the electric or magnetic fields generated by neuronal activity (EEG, magnetencephalography [MEG]) and those measuring the haemodynamic or metabolic sequelae of neuronal activity (positron emission tomography [PET], functional magnetic resonance imaging [fMRI]). Out of these techniques, the following two will be discussed in detail: fMRI and PET. Although functional neuroimaging is able to acquire images of the brain engaged in consolidating or retrieving memories, these processes are not clearly visible in the data. Statistical techniques are needed to reduce the complexity of the data and to extract the processes of interest. This article outlines the experimental and analytical procedures of neuroimaging studies with PET and fMRI. We will use a PET-study on episodic memory in human volunteers to illustrate design, analysis, and interpretation of functional imaging studies on memory.     

Neural Responses to Truth Telling and Risk Propensity under Asymmetric Information

Trust is multi-dimensional because it can be characterized by subjective trust, trust antecedent, and behavioral trust. Previous research has investigated functional brain responses to subjective trust (e.g., a judgment of trustworthiness) or behavioral trust (e.g., decisions to trust) in perfect information, where all relevant information is available to all participants. In contrast, we conducted a novel examination of the patterns of functional brain activity to a trust antecedent, specifically truth telling, in asymmetric information, where one individual has more information than others, with the effect of varying risk propensity. We used functional magnetic resonance imaging (fMRI) and recruited 13 adults, who played the Communication Game, where they served as the “Sender” and chose either truth telling (true advice) or lie telling (false advice) regarding the best payment allocation for their partner. Our behavioral results revealed that subjects with recreational high risk tended to choose true advice. Moreover, fMRI results yielded that the choices of true advice were associated with increased cortical activation in the anterior rostral medial and frontopolar prefrontal cortices, middle frontal cortex, temporoparietal junction, and precuneus. Furthermore, when we specifically evaluated a role of the bilateral amygdala as the region of interest (ROI), decreased amygdala response was associated with high risk propensity, regardless of truth telling or lying. In conclusion, our results have implications for how differential functions of the cortical areas may contribute to the neural processing of truth telling.     

使用非侵入的神经影像方法解码人类思维

随着神经影像技术的发展,“读脑机器”在不久的将来可能会变成现实。在众多实现“读脑机器”的技术中,使用基于血氧水平依赖的脑功能磁共振技术的神经解码方法则是非常有希望的一种技术。在本报告中,我们结合我们实验室最近开展的两个研究工作,说明了使用功能磁共振技术进行神经解码的一般方法及其应用。本领域的发展很快,所有的这些工作让我们对发明“读脑机器”充满了期待。但是,与此同时,我们也应该看到目前还存在着很多技术的局限和挑战。本报告的最后,我们也对这些局限和挑战进行了一些讨论。