Different Roles of COMT and HTR2A Genotypes in Working Memory Subprocesses

Working memory is linked to the functions of the frontal areas, in which neural activity is mediated by dopaminergic and serotonergic tones. However, there is no consensus regarding how the dopaminergic and serotonergic systems influence working memory subprocesses. The present study used an imaging genetics approach to examine the interaction between neurochemical functions and working memory performance. We focused on functional polymorphisms of the catechol-O-methyltransferase (COMT) Val¹⁵⁸Met and serotonin 2A receptor (HTR2A) -1438G/A genes, and devised a delayed recognition task to isolate the encoding, retention, and retrieval processes for visual information. The COMT genotypes affected recognition accuracy, whereas the HTR2A genotypes were associated with recognition response times. Activations specifically related to working memory were found in the right frontal and parietal areas, such as the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), anterior cingulate cortex (ACC), and inferior parietal lobule (IPL). MFG and ACC/IPL activations were sensitive to differences between the COMT genotypes and between the HTR2A genotypes, respectively. Structural equation modeling demonstrated that stronger connectivity in the ACC-MFG and ACC-IFG networks is related to better task performance. The behavioral and fMRI results suggest that the dopaminergic and serotonergic systems play different roles in the working memory subprocesses and modulate closer cooperation between lateral and medial frontal activations.     

The neural basis of metacognitive ability

Ability in various cognitive domains is often assessed by measuring task performance, such as the accuracy of a perceptual categorization. A similar analysis can be applied to metacognitive reports about a task to quantify the degree to which an individual is aware of his or her success or failure. Here, we review the psychological and neural underpinnings of metacognitive accuracy, drawing on research in memory and decision-making. These data show that metacognitive accuracy is dissociable from task performance and varies across individuals. Convergent evidence indicates that the function of the rostral and dorsal aspect of the lateral prefrontal cortex (PFC) is important for the accuracy of retrospective judgements of performance. In contrast, prospective judgements of performance may depend upon medial PFC. We close with a discussion of how metacognitive processes relate to concepts of cognitive control, and propose a neural synthesis in which dorsolateral and anterior prefrontal cortical subregions interact with interoceptive cortices (cingulate and insula) to promote accurate judgements of performance.     

Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials

Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit—Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit—Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks—Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation—Dentist). The participants’ memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring whereas retrieval success was reflected in an anterior positive slow wave.     

Electrophysiological correlates of strategic monitoring in event-based and time-based prospective memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks.The addition of an event-based or a time-based PM task to an ongoing activity led to a similar sustained positive modulation of the ERPs in the ongoing trials, mainly expressed over prefrontal and frontal regions. This modulation might index the retrieval mode mechanism, similarly engaged in the two PM tasks. On the other hand, two further ERP modulations were shown specifically in an event-based PM task. An increased positivity was shown at 400-600 ms post-stimulus over occipital and parietal regions, and might be related to target checking. Moreover, an early modulation at 130-180 ms post-stimulus seems to reflect the recruitment of attentional resources for being ready to respond to the event-based PM cue. This latter modulation suggests the existence of a third mechanism specific for the event-based PM; that is, the "readiness mode".     

Mental Rotational Ability Is Correlated with Spatial but Not Verbal Working Memory Performance and P300 Amplitude in Males

This study investigated how both sex and individual differences in a mental rotation test (MRT) influence performance on working memory (WM). To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory.     

The Influence of a Working Memory Task on Affective Perception of Facial Expressions

In a dual-task paradigm, participants performed a spatial location working memory task and a forced two-choice perceptual decision task (neutral vs. fearful) with gradually morphed emotional faces (neutral ∼ fearful). Task-irrelevant word distractors (negative, neutral, and control) were experimentally manipulated during spatial working memory encoding. We hypothesized that, if affective perception is influenced by concurrent cognitive load using a working memory task, task-irrelevant emotional distractors would bias subsequent perceptual decision-making on ambiguous facial expression. We found that when either neutral or negative emotional words were presented as task-irrelevant working-memory distractors, participants more frequently reported fearful face perception - but only at the higher emotional intensity levels of morphed faces. Also, the affective perception bias due to negative emotional distractors correlated with a decrease in working memory performance. Taken together, our findings suggest that concurrent working memory load by task-irrelevant distractors has an impact on affective perception of facial expressions.     

Prospective Memory Function in Late Adulthood: Affect at Encoding and Resource Allocation Costs

Some studies have found that prospective memory (PM) cues which are emotionally valenced influence age effects in prospective remembering, but it remains unclear whether this effect reflects the operation of processes implemented at encoding or retrieval. In addition, none of the prior ageing studies of valence on PM function have examined potential costs of engaging in different valence conditions, or resource allocation trade-offs between the PM and the ongoing task. In the present study, younger, young-old and old-old adults completed a PM task in which the valence of the cues varied systematically (positive, negative or neutral) at encoding, but was kept constant (neutral) at retrieval. The results indicated that PM accuracy did not vary as a function of affect at encoding, and that this effect did not interact with age group. There was also no main or interaction effect of valence on PM reaction time in PM cue trials, indicating that valence costs across the three encoding conditions were equivalent. Old-old adults’ PM accuracy was reduced relative to both young-old and younger adults. Prospective remembering incurred dual-task costs for all three groups. Analyses of reaction time data suggested that for both young-old and old-old, these costs were greater, implying differential resource allocation cost trade-offs. However, when reaction time data were expressed as a proportional change that adjusted for the general slowing of the older adults, costs did not differ as a function of group.     

The Right Frontopolar Cortex Is Involved in Visual-Spatial Prospective Memory

The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10, right BA10 and CZ (control condition). In the prospective memory procedure, sequences of four spatial positions (black squares) each were presented. During the inter-sequence delay, subjects had to reproduce the sequence in the observed order (ongoing task forward) or the reverse order (backward). At the occurrence of a target position, subjects had to press a key on the keyboard (prospective memory score). Recall and recognition of the target positions were also tested. We found that prospective memory accuracy was lower after theta-burst stimulation over right BA10 than CZ (p<0.01), whereas it was comparable in left BA10 and CZ conditions. No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance. Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospective memory. In the context of previous data providing evidence for left BA 10 involvement in verbal prospective memory, our results also suggest material-specific lateralization of prospective memory processes in BA 10.     

Closing the Gap between the Inside and the Outside: Interoceptive Sensitivity and Social Distances

Humans’ ability to represent their body state from within through interoception has been proposed to predict different aspects of human cognition and behaviour. We focused on the possible contribution of interoceptive sensitivity to social behaviour as mediated by adaptive modulation of autonomic response. We, thus, investigated whether interoceptive sensitivity to one''s heartbeat predicts participants'' autonomic response at different social distances. We measured respiratory sinus arrhythmia (RSA) during either a Social or a Non-social task. In the Social task each participant viewed an experimenter performing a caress-like movement at different distances from their hand. In the Non-social task a metal stick was moved at the same distances from the participant''s hand. We found a positive association between interoceptive sensitivity and autonomic response only for the social setting. Moreover, only good heartbeat perceivers showed higher autonomic response 1) in the social compared to the non-social setting, 2) specifically, when the experimenter''s hand was moving at boundary of their peripersonal space (20 cm from the participant''s hand). Our findings suggest that interoceptive sensitivity might contribute to interindividual differences concerning social attitudes and interpersonal space representation via recruitment of different adaptive autonomic response strategies.     

Free and Cued Recall Memory in Parkinson’s Disease Associated with Amnestic Mild Cognitive Impairment

The hypothesis has been advanced that memory disorders in individuals with Parkinson’s disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients’ performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning.     

The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

Introduction

The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time.

Methods

To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks.

Results

We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks.

Conclusions

Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.     

Evidence for Anomalous Network Connectivity during Working Memory Encoding in Schizophrenia: An ICA Based Analysis

Background

Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by “functional connectivity” analyses.

Methodology/Principal Findings

We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct “normal” encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase.

Conclusions/Significance

This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.     

Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli

Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli.     

Effects of aversive stimuli on prospective memory. An event-related fMRI study

Prospective memory (PM) describes the ability to execute a previously planned action at the appropriate point in time. Although behavioral studies clearly showed that prospective memory performance is affected by the emotional significance attributed to the intended action, no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance. The general aim of the present study was to explore brain regions involved in prospective memory processes when PM cues are associated with emotional stimuli. In particular, based on the hypothesised critical role of the prefrontal cortex in prospective memory in the presence of emotionally salient stimuli, we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus. To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions. Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area (BA 10) and in the left caudate nucleus. Moreover a temporal shift between the response of the caudate nucleus that preceded that of aPFC was observed. These findings suggest that the caudate nucleus might provide an early analysis of the affective properties of the stimuli, whereas the anterior lateral prefrontal cortex (BA10) would be involved in a slower and more deliberative analysis to guide goal-directed behaviour.     

Phasic and Tonic Pain Differentially Impact the Interruptive Function of Pain

The interruptive effect of painful experimental stimulation on cognitive processes is a well-known phenomenon. This study investigated the influence of pain duration on the negative effects of pain on cognition. Thirty-four healthy volunteers performed a rapid serial visual presentation task (RSVP) in which subjects had to detect (visual detection task) and count the occurrence of a target letter (working memory task) in two separate sessions while being stimulated on the left volar forearm with either short (2 sec) or long (18 sec) painful heat stimuli of equal subjective intensity. The results show that subjects performed significantly worse in the long pain session as indexed by decreased detection and counting performance. Interestingly, this effect on performance was also observed during control trials of the long pain session in which participants did not receive any painful stimulation. Moreover, subjects expected long painful stimulation to have a greater impact on their performance and individual expectation correlated with working memory performance. These findings suggest that not only the length of painful stimulation but also its expected ability to impair cognitive functioning might influence the interruptive function of pain. The exact relevance of expectation for the detrimental effects of pain on cognitive processes needs to be explored in more detail in future studies.     

Content-specific working memory modulation of the attentional blink

Three experiments were conducted to investigate the effects of working memory content on temporal attention in a rapid serial visual presentation attentional blink paradigm. It was shown that categorical similarity between working memory content and the target stimuli pertaining to the attentional task (both digits) increased attentional blink magnitude compared to a condition in which this similarity was absent (colors and digits, respectively). This effect was only observed when the items in working memory were not presented as conjunctions of the involved categories (i.e., colored digits). This suggested that storage and retrieval from working memory was at least preferentially conjunctive in this case. It was furthermore shown that the content of working memory enhanced the identification rate of the second target, by means of repetition priming, when inter-target lag was short and the attentional blink was in effect. The results are incompatible with theories of temporal attention that assume working memory has no causal role in the attentional blink and support theories that do.     

Psychological and stabilographic features of healthy persons with different capabilities of performing dual tasks

A dual task study including control of postural balance and counting was conducted on 40 healthy subjects (with an average age of 29.8 ± 2.47 years) along with a psychological examination that included estimation of the working memory, attention, and the time of attention switch. Three types of dual task performance were observed: worsening of either one or both components of the dual task, improvement of one component, and improvement of both components of the dual task. 30% of participants performed a dual task better than isolated tasks. Successful performance in the dual task correlated with the higher volume of spatial and working memory, attention, and a rapid switch of attention. The speed of sway of the center of pressure (CoP) negatively correlated with the speed of attention switch, while the amplitude of the CoP shift in the frontal plane negatively correlated with the volume of spatial and working memory. These data suggest involvement of the cognitive resources in controlling the upright balance and a high degree of motor automatism when the dual tasks are successfully performed. Our experimental paradigm is expected to be helpful in predicting individual performance in situations with high information loads.     

Valenced Cues and Contexts Have Different Effects on Event-Based Prospective Memory

This study examined the separate influence and joint influences on event-based prospective memory task performance due to the valence of cues and the valence of contexts. We manipulated the valence of cues and contexts with pictures from the International Affective Picture System. The participants, undergraduate students, showed higher performance when neutral compared to valenced pictures were used for cueing prospective memory. In addition, neutral pictures were more effective as cues when they occurred in a valenced context than in the context of neutral pictures, but the effectiveness of valenced cues did not vary across contexts that differed in valence. The finding of an interaction between cue and context valence indicates that their respective influence on event-based prospective memory task performance cannot be understood in isolation from each other. Our findings are not consistent with by the prevailing view which holds that the scope of attention is broadened and narrowed, respectively, by positively and negatively valenced stimuli. Instead, our findings are more supportive of the recent proposal that the scope of attention is determined by the motivational intensity associated with valenced stimuli. Consistent with this proposal, we speculate that the motivational intensity associated with different retrieval cues determines the scope of attention, that contexts with different valence values determine participants’ task engagement, and that prospective memory task performance is determined jointly by attention scope and task engagement.     

Changes in Brain Network Efficiency and Working Memory Performance in Aging

Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.