The Dorsal Attention Network Reflects Both Encoding Load and Top-down Control during Working Memory.

The dorsal attention network is consistently involved in verbal and visual working memory (WM) tasks and has been associated with task-related, top-down control of attention. At the same time, WM capacity has been shown to depend on the amount of information that can be encoded in the focus of attention independently of top-down strategic control. We examined the role of the dorsal attention network in encoding load and top-down memory control during WM by manipulating encoding load and memory control requirements during a short-term probe recognition task for sequences of auditory (digits, letters) or visual (lines, unfamiliar faces) stimuli. Encoding load was manipulated by presenting sequences with small or large sets of memoranda while maintaining the amount of sensory stimuli constant. Top-down control was manipulated by instructing participants to passively maintain all stimuli or to selectively maintain stimuli from a predefined category. By using ROI and searchlight multivariate analysis strategies, we observed that the dorsal attention network encoded information for both load and control conditions in verbal and visuospatial modalities. Decoding of load conditions was in addition observed in modality-specific sensory cortices. These results highlight the complexity of the role of the dorsal attention network in WM by showing that this network supports both quantitative and qualitative aspects of attention during WM encoding, and this is in a partially modality-specific manner.

Fluctuations of Attentional Networks and Default Mode Network during the Resting State Reflect Variations in Cognitive States: Evidence from a Novel Resting-state Experience Sampling Method.

Neuroimaging studies have revealed the recruitment of a range of neural networks during the resting state, which might reflect a variety of cognitive experiences and processes occurring in an individual's mind. In this study, we focused on the default mode network (DMN) and attentional networks and investigated their association with distinct mental states when participants are not performing an explicit task. To investigate the range of possible cognitive experiences more directly, this study proposes a novel method of resting-state fMRI experience sampling, informed by a phenomenological investigation of the fluctuation of mental states during the resting state. We hypothesized that DMN activity would increase as a function of internal mentation and that the activity of dorsal and ventral networks would indicate states of top-down versus bottom-up attention at rest. Results showed that dorsal attention network activity fluctuated as a function of subjective reports of attentional control, providing evidence that activity of this network reflects the perceived recruitment of controlled attentional processes during spontaneous cognition. Activity of the DMN increased when participants reported to be in a subjective state of internal mentation, but not when they reported to be in a state of perception. This study provides direct evidence for a link between fluctuations of resting-state neural activity and fluctuations in specific cognitive processes.

Cross-Modal Decoding of Neural Patterns Associated with Working Memory: Evidence for Attention-Based Accounts of Working Memory.

Recent studies suggest common neural substrates involved in verbal and visual working memory (WM), interpreted as reflecting shared attention-based, short-term retention mechanisms. We used a machine-learning approach to determine more directly the extent to which common neural patterns characterize retention in verbal WM and visual WM. Verbal WM was assessed via a standard delayed probe recognition task for letter sequences of variable length. Visual WM was assessed via a visual array WM task involving the maintenance of variable amounts of visual information in the focus of attention. We trained a classifier to distinguish neural activation patterns associated with high- and low-visual WM load and tested the ability of this classifier to predict verbal WM load (high-low) from their associated neural activation patterns, and vice versa. We observed significant between-task prediction of load effects during WM maintenance, in posterior parietal and superior frontal regions of the dorsal attention network; in contrast, between-task prediction in sensory processing cortices was restricted to the encoding stage. Furthermore, between-task prediction of load effects was strongest in those participants presenting the highest capacity for the visual WM task. This study provides novel evidence for common, attention-based neural patterns supporting verbal and visual WM.

Does sleep promote false memories?

Memory is constructive in nature so that it may sometimes lead to the retrieval of distorted or illusory information. Sleep facilitates accurate declarative memory consolidation but might also promote such memory distortions. We examined the influence of sleep and lack of sleep on the cerebral correlates of accurate and false recollections using fMRI. After encoding lists of semantically related word associates, half of the participants were allowed to sleep, whereas the others were totally sleep deprived on the first postencoding night. During a subsequent retest fMRI session taking place 3 days later, participants made recognition memory judgments about the previously studied associates, critical theme words (which had not been previously presented during encoding), and new words unrelated to the studied items. Sleep, relative to sleep deprivation, enhanced accurate and false recollections. No significant difference was observed in brain responses to false or illusory recollection between sleep and sleep deprivation conditions. However, after sleep but not after sleep deprivation (exclusive masking), accurate and illusory recollections were both associated with responses in the hippocampus and retrosplenial cortex. The data suggest that sleep does not selectively enhance illusory memories but rather tends to promote systems-level consolidation in hippocampo-neocortical circuits of memories subsequently associated with both accurate and illusory recollections. We further observed that during encoding, hippocampal responses were selectively larger for items subsequently accurately retrieved than for material leading to illusory memories. The data indicate that the early organization of memory during encoding is a major factor influencing subsequent production of accurate or false memories.

Abnormal neural filtering of irrelevant visual information in depression.

The pathophysiology of major depressive disorder (MDD) includes both affective and cognitive dysfunctions. We aimed to clarify how regions regulating affective processing interact with those involved in attention, and how such interaction impacts perceptual processing within sensory cortices. Based on previous work showing that top-down influences from attention can determine the processing of external inputs within early sensory cortices, we tested with functional magnetic resonance imaging (fMRI) whether MDD alters attentional ("top-down") effects on the neural filtering of irrelevant, nonemotional visual stimuli. The present fMRI study was conducted in 14 nonmedicated patients with a first episode of unipolar MDD and 14 matched controls. During scanning, subjects performed two tasks imposing two different levels of attentional load at fixation (easy or difficult), while irrelevant colored stimuli were presented in the periphery. Analyses of fMRI data revealed that MDD patients show (1) an abnormal filtering of irrelevant information in visual cortex, (2) an altered functional connectivity between frontoparietal networks and visual cortices, and (3) a hyperactivity in subgenual cingulate/medial orbitofrontal cortex that was modulated by attentional load. These results demonstrate that biological abnormalities contribute to the cognitive deficits seen in major depression, and clarify how neural networks implicated in mood regulation influence executive control and perceptual processes. These findings not only improve our understanding of the pathophysiological mechanisms underlying cognitive dysfunctions in MDD, but also shed new light on the interaction between cognition and mood regulation.

The neural correlates of verbal short-term memory in Alzheimer's disease: an fMRI study.

Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in Alzheimer's disease patients. In this fMRI study, we examined alterations in brain activation patterns during a verbal short-term memory recognition task, by differentiating encoding and retrieval phases. Sixteen mild Alzheimer's disease patients and 16 elderly controls were presented with lists of four words followed, after a few seconds, by a probe word. Participants had to judge whether the probe matched one of the items of the memory list. In both groups, the short-term memory task elicited a distributed fronto-parieto-temporal activation that encompassed bilateral inferior frontal, insular, supplementary motor, precentral and postcentral areas, consistent with previous studies of verbal short-term memory in young subjects. Most notably, Alzheimer's disease patients showed reduced activation in several regions during the encoding phase, including the bilateral middle frontal and the left inferior frontal gyri (associated with executive control processes) as well as the transverse temporal gyri (associated with phonological processing). During the recognition phase, we found decreased activation in the left supramarginal gyrus and the right middle frontal gyrus in Alzheimer's disease patients compared with healthy seniors, possibly related to deficits in manipulation and decision processes for phonological information. At the same time, Alzheimer's disease patients showed increased activation in several brain areas, including the left parahippocampus and hippocampus, suggesting that Alzheimer's disease patients may recruit alternative recognition mechanisms when performing a short-term memory task. Overall, our results indicate that Alzheimer's disease patients show differences in the functional networks underlying memory over short delays, mostly in brain areas known to support phonological processing or executive functioning.

Consciousness as recursive, spatiotemporal self-location.

At the phenomenal level, consciousness arises in a consistently coherent fashion as a singular, unified field of recursive self-awareness (subjectivity) with explicitly orientational characteristics--that of a subject located both spatially and temporally in an egocentrically-extended domain. Understanding these twin elements of consciousness begins with the recognition that ultimately (and most primitively), cognitive systems serve the biological self-regulatory regime in which they subsist. The psychological structures supporting self-located subjectivity involve an evolutionary elaboration of the two basic elements necessary for extending self-regulation into behavioral interaction with the environment: an orientative reference frame which consistently structures ongoing interaction in terms of controllable spatiotemporal parameters, and processing architecture that relates behavior to homeostatic needs via feedback. Over time, constant evolutionary pressures for energy efficiency have encouraged the emergence of anticipative feedforward processing mechanisms, and the elaboration, at the apex of the sensorimotor processing hierarchy, of self-activating, highly attenuated recursively-feedforward circuitry processing the basic orientational schema independent of external action output. As the primary reference frame of active waking cognition, this recursive self-locational schema processing generates a zone of subjective self-awareness in terms of which it feels like something to be oneself here and now. This is consciousness-as-subjectivity.

Neural substrates of phonological and lexicosemantic representations in Alzheimer's disease.

The language profile of patients suffering from Alzheimer's disease (AD) is characterized not only by lexicosemantic impairments but also by phonological deficits, as shown by an increasing number of neuropsychological studies. This study explored the functional neural correlates underlying phonological and lexicosemantic processing in AD. Using H(215)O PET functional brain imaging, a group of mild to moderate AD patients and a group of age-matched controls were asked to repeat four types of verbal stimuli: words, wordlike nonwords (WL+), non-wordlike nonwords (WL-) and simple vowels. The comparison between the different conditions allowed us to determine brain activation preferentially associated with lexicosemantic or phonological levels of language representations. When repeating words, AD patients showed decreased activity in the left temporo-parietal and inferior frontal regions relative to controls, consistent with distorted lexicosemantic representations. Brain activity was abnormally increased in the right superior temporal area during word repetition, a region more commonly associated with perceptual-phonological processing. During repetition of WL+ and WL- nonwords, AD patients showed decreased activity in the middle part of the superior temporal gyrus, presumably associated with sublexical phonological information; at the same time, AD patients showed larger activation than controls in the inferior temporal gyrus, typically associated with lexicosemantic levels of representation. Overall, the results suggest that AD patients use altered pathways to process phonological and lexicosemantic information, possibly related to a progressive loss of specialization of phonological and lexicosemantic neural networks.

Are the carrot and the stick the two sides of same coin? A neural examination of approach/avoidance motivation during cognitive performance.

The present study examined neural circuit activity in a working memory (WM) task under conditions of approach and avoidance motivation. Eighteen participants were scanned with functional MRI while they performed a 3-back WM task under three conditions: in an avoidance condition incorrect responses were punished with monetary loss; in an approach condition correct responses were rewarded with monetary gain; in a neutral control condition there was no monetary incentive. Compared with the control condition, activation in fronto-parietal areas - which are associated with WM processing - was increased in both the approach and avoidance conditions. The results suggest that both approach and avoidance motivation increase task-related cognitive activation.

Predicting progression to dementia in elderly subjects with mild cognitive impairment using both cognitive and neuroimaging predictors.

The objective of this work was to assess the predictive accuracy of targeted neuroimaging and neuropsychological measures for the detection of incipient dementia in individuals with mild cognitive impairment (MCI), and to examine the potential benefit of combining both classes of measures. Baseline MRI measures included hippocampal volume, cortical thickness, and white matter hyperintensities. Neuropsychological assessment focused on different aspects of episodic memory (i.e., familiarity, free recall, and associative memory) and executive control functions (i.e., working memory, switching, and planning). Global and regional cortical thinning was observed in MCI patients who progressed to dementia compared to those who remained stable, whereas no differences were found between groups for baseline hippocampal volume and white matter hyperintensities. The strongest neuroimaging predictors were baseline cortical thickness in the right anterior cingulate and middle frontal gyri. For cognitive predictors, we found that deficits in both free recall and recognition episodic memory tasks were highly suggestive of progression to dementia. Cortical thinning in the right anterior cingulate gyrus, combined to controlled and familiarity-based retrieval deficits, achieved a classification accuracy of 87.5%, a specificity of 90.9%, and a sensitivity of 83.3%. This predictive model including both classes of measures provided more accurate predictions than those based on neuroimaging or cognitive measures alone. Overall, our findings suggest that detecting preclinical Alzheimer's disease is probably best accomplished by combining complementary information from targeted neuroimaging and cognitive classifiers, and highlight the importance of taking into account both structural and functional changes associated with the disease.

Reduced multisensory facilitation in persons with autism.

Although the literature concerning auditory and visual perceptual capabilities in the autism spectrum is growing, our understanding of multisensory integration (MSI) is rather limited. In the present study, we assessed MSI in autism by measuring whether participants benefited from an auditory cue presented in synchrony with the color change of a target during a complex visual search task. The synchronous auditory pip typically increases search efficacy (pip and pop effect), indicative of the beneficial use of sensory input from both modalities. We found that for conditions without auditory information, autistic participants were better at visual search compared to neurotypical participants. Importantly, search efficiency was increased by the presence of auditory pip for neurotypical participants only. The simultaneous occurrence of superior unimodal performance with altered audio-visual integration in autism suggests autonomous sensory processing in this population.

Lack of semantic priming effects in famous person recognition in Mild Cognitive Impairment.

INTRODUCTION: Growing evidence indicates that individuals with Mild Cognitive Impairment (MCI) manifest semantic deficits that are often more severe for items that are characterized by a unique semantic and lexical association, such as famous people and famous buildings, than common concepts, such as objects. However, it is still controversial whether the semantic deficits observed in MCI are determined by a degradation of semantic information or by a deficit in intentional access to semantic knowledge. Here we used a semantic priming task in order to assess the integrity of the semantic system without requiring explicit access to this system. This paradigm may provide new insights in clarifying the nature of the semantic deficits in MCI. METHODS: We assessed the semantic and repetition priming effect in 13 individuals with MCI and 13 age-matched controls who engaged in a familiarity judgment task of famous names. In the semantic priming condition, the prime was the name of a member of the same occupation category as the target (Tom Cruise-Brad Pitt), while in the repetition priming condition the prime was the same name as the target (Charlie Chaplin-Charlie Chaplin). RESULTS: The results showed a defective priming effect in MCI in the semantic but not in the repetition priming condition. Specifically, when compared to controls, MCI patients did not show a facilitation effect in responding to the same occupation prime-target pairs, but they showed an equivalent facilitation effect when the target was the same name as the prime. CONCLUSION: The present results provide support to the hypothesis that the semantic impairments observed in MCI cannot be uniquely ascribed to a deficit in intentional access to semantic information. Instead, these findings point to the semantic nature of these deficits and, in particular, to a degraded representation of semantic information concerning famous people.

Abnormal temporal dynamics of visual attention in Alzheimer's disease and in dementia with Lewy bodies.

Although attentional control processes are disproportionately impaired in dementia with Lewy bodies (DLB) compared with dementia of the Alzheimer type (DAT), previous studies have not compared directly the temporal dynamics of visual attention in DLB and DAT. We examined the magnitude of the attentional blink (AB) effect in these patients, to determine the degree to which each patient group exhibited a deficit in selecting and processing visual stimuli presented in rapid succession. Eighteen DAT, 15 DLB patients, and 33 elderly controls were tested in a rapid serial visual presentation task. Participants were asked to report 1 (single-target condition) or 2 target letters (dual-target condition) embedded in a sequence of digit distracters. The temporal dynamics of visual attention was examined by varying the number of intervening distracters between the 2 targets in the dual-target condition and by estimating the attentional blink effect as the decline in the ability to report the second target correctly after successfully identifying the first. Patients with DLB performed significantly worse than patients with DAT and controls in both the single and dual-targets conditions. In contrast, DAT patients showed a selective impairment in the dual-target condition as compared with controls. As predicted, we found that both patients with DAT and DLB showed a more pronounced and protracted attentional blink than controls, indicating a reduced ability to re-engage attention on the second target. Furthermore, when DAT and DLB patients were able to report the second target, they frequently failed to identify the first, an effect that was absent in elderly controls and particularly large and long-lasting in DLB patients. This study suggests that both DLB and DAT patients show abnormal temporal dynamics of visual selective attention, presumably due to a greater intertarget competition for limited processing capacity. More generally, these findings reinforce the notion that deficits of attentional control processes are more severe in DLB patients as compared with DAT patients.

Impaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease.

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD.

Perspective taking to assess self-personality: what's modified in Alzheimer's disease?

Personality changes are frequently described by caregivers of patients with Alzheimer's disease, while they are less often reported by the patients. This relative anosognosia of Alzheimer disease (AD) patients for personality changes might be related to impaired self-judgment and to decreased ability to understand their caregiver's perspective. To investigate this issue, we explored the cerebral correlates of self-assessment and perspective taking in patients with mild AD, elderly and young volunteers. All subjects assessed relevance of personality traits adjectives for self and a relative, taking either their own or their relative's perspective, during a functional imaging experiment. The comparison of subject's and relative's answers provided congruency scores used to assess self-judgment and perspective taking performance. The self-judgment "accuracy" score was diminished in AD, and when patients assessed adjectives for self-relevance, they predominantly activated bilateral intraparietal sulci (IPS). Previous studies associated IPS activation with familiarity judgment, which AD patients would use more than recollection when retrieving information to assess self-personality. When taking a third-person perspective, patients activated prefrontal regions (similarly to young volunteers), while elderly controls recruited visual associative areas (also activated by young volunteers). This suggests that mild AD patients relied more on reasoning processes than on visual imagery of autobiographical memories to take their relative's perspective. This strategy may help AD patients to cope with episodic memory impairment even if it does not prevent them from making some mind-reading errors.

A multicomponent exploration of verbal short-term storage deficits in normal aging and Alzheimer's disease.

Although many studies have shown diminished performance in verbal short-term memory tasks in normal aging and Alzheimer's disease (AD), the cognitive processes responsible for this verbal short-term storage (STS) impairment are still unclear for both populations. We explored verbal STS functioning in patients with AD, elderly participants, and young participants, by investigating a series of processes that could underlie STS impairments in normal elderly and AD populations. The processes we investigated were (a) the influence of lexical and sublexical language knowledge on short-term storage performance, (b) functioning of the phonological loop component via word length and phonological similarity effects, and (c) executive control processes (coordination and integration). For the AD and elderly groups, the influence of language knowledge on verbal STS performance and the functioning of the phonological loop were preserved. In contrast, the AD group showed deficits for coordination and integration processes. Our results suggest that the verbal STS deficit observed in AD patients is related to impaired executive control processes. On the other hand, language-related processes underlying passive storage capacity seem to be preserved.

Orbitofrontal dysfunction related to both apathy and disinhibition in frontotemporal dementia.

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, -24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, -22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD.