Executive functioning moderates the decline of retrieval fluency in time.

Prevailing theoretical accounts consider that automatic and controlled processes are uniformly engaged in memory retrieval across performance of the semantic verbal fluency (SVF) task. We tested this proposal against the alternative, namely that a rapid automatic retrieval, exploiting stable associative structure in the early stages of the performance, is followed by a slower, more executively demanding, retrieval in later stages. Eighty-five healthy adults completed low- and high-demand SVF tasks that were assessed for retrieval rate, response typicality, and inter-response similarity across the performance. Additional measures of executive functioning were collected to estimate individual differences in executive control. We found that decrease in fluency in time was associated with lower typicality and weaker semantic similarity of the responses. Critically, the time-dependent retrieval slowing was steeper in individuals with less efficient interference control, particularly in high-demand SVF tasks. Steeper retrieval slowing was also associated with poorer working-memory capacity. Our findings show that the relative contribution of automatic and controlled processes to semantic retrieval changes with associative sparsity over time and across task demands, and provide implications for the use of SVF tasks in clinical assessment.

Differential effects of executive load on automatic versus controlled semantic memory retrieval.

Growing evidence indicates that a domain-general executive control supports semantic memory retrieval, yet the nature of this interaction remains elusive. To shed light on such control mechanisms, we conducted two dual-task experiments loading distinct executive capacities (working memory maintenance, monitoring, and switching), while participants carried out automatic (free-associative) and controlled (dissociative) word retrieval tasks. We found that these forms of executive load interfered with retrieval fluency in both tasks, but these negative effects were more pronounced for the dissociative performance. Together, these findings indicate that the domain-general executive control supports accessing contextually relevant knowledge as well as the inhibition of automatically activated but task-inappropriate retrieval candidates, putatively via an adaptive gating of semantic activation and interference control. Moreover, the processing costs related to retrieval inhibition and switching were negatively correlated, suggesting a trade-off between the ability to constrain semantic activation (i.e., inhibition) and the ability to initiate flexible transitions between semantic sets (i.e., switching), which may thus represent two complementary control functions governing semantic memory retrieval.

Response modularity moderates how executive control aids fluent semantic memory retrieval.

ABSTRACTEmerging work in semantic cognition has begun to elucidate the interaction between the structure of semantic memory and processes mediating goal-directed memory retrieval. Despite having essential implications for basic and applied research, these objectives remain neglected in both the assessment and interpretation of semantic verbal fluency (SVF) tasks. To test the association between semantic structure and the controlled processes underlying verbal fluency, we assessed how the degree of partitioning (modularity) of SVF responses into semantic clusters moderates the relationship of retrieval fluency with working memory and interference control capacities. We found that working memory capacity predicted retrieval fluency in individuals whose SVF responses were arranged in fine-grained semantic clusters (high modularity), whereas interference control was more predictive of retrieval fluency for individuals who delivered responses of low modularity. Our data support the presumed role of working memory and interference control in SVF and provide novel evidence that relative demands on these capacities are predicted by the organisation of semantic knowledge.

Beyond Sharing Unpleasant Affect-Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain.

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.

The structure of semantic representation shapes controlled semantic retrieval.

An essential aim in the research on semantic cognition is to understand the interplay between the structure of semantic representation and controlled processes that operate on it to generate flexible behaviours. To evaluate the link between semantic network connectivity and semantic control functions (semantic inhibition and switching), we employed a network theory approach and revealed that controlled semantic processing was reliably associated with connectivity of conceptual representation. In particular, our results show that efficient information flow afforded by high connectivity of semantic network is coupled with superior switching but poor inhibition ability. These findings suggest that the network architectures that facilitate efficient semantic activation spreading aid flexible transitions between semantic clusters but impede inhibition employed to suppress inappropriate or interfering semantic representations. Overall, our study provides a novel insight into the mechanisms underlying controlled semantic processing that is recruited to disentangle from habitual structure of semantic representation.

Duration of Social Isolation Affects Production of Nitric Oxide in the Rat Brain.

Social isolation deprives rodents of social interactions that are critical for normal development of brain and behavior. Several studies have indicated that postweaning isolation rearing may affect nitric oxide (NO) production. The aim of this study was to compare selected behavioral and biochemical changes related to NO production in the brain of rats reared in social isolation for different duration. At the age of 21 days, male Sprague Dawley rats were randomly assigned into four groups reared in isolation or socially for 10 or 29 weeks. At the end of the rearing, open-field and prepulse inhibition (PPI) tests were carried out. Furthermore, in several brain areas we assessed NO synthase (NOS) activity, protein expression of nNOS and iNOS isoforms and the concentration of conjugated dienes (CD), a marker of oxidative damage and lipid peroxidation. Social isolation for 10 weeks resulted in a significant decrease in PPI, which was accompanied by a decrease in NOS activity in the cerebral cortex and the cerebellum, an increase in iNOS in the hippocampus and an increase in CD concentration in cortex homogenate. On the other hand, a 29 week isolation had an opposite effect on NOS activity, which increased in the cerebral cortex and the cerebellum in animals reared in social isolation, accompanied by a decrease in CD concentration. The decrease in NOS activity after 10 weeks of isolation might have been caused by chronic stress induced by social isolation, which has been documented in previous studies. The increased oxidative state might result in the depleted NO bioavailability, as NO reacts with superoxide radical creating peroxynitrite. After 29 weeks of isolation, this loss of NO might be compensated by the subsequent increase in NOS activity.

Increasing self-other bodily overlap increases sensorimotor resonance to others' pain.

Empathy for another person's pain and feeling pain oneself seem to be accompanied by similar or shared neural responses. Such shared responses could be achieved by mapping the bodily states of others onto our own bodily representations. We investigated whether sensorimotor neural responses to the pain of others are increased when experimentally reducing perceived bodily distinction between the self and the other. Healthy adult participants watched video clips of the hands of ethnic ingroup or outgroup members being painfully penetrated by a needle syringe or touched by a cotton swab. Manipulating the video presentation to create a visuospatial overlap between the observer's and the target's hand increased the perceived bodily self-attribution of the target's hand. For both ingroup and outgroup targets, this resulted in increased neural responses to the painful injections (compared with nonpainful contacts), as indexed by desynchronizations of central mu and beta scalp rhythms recorded using electroencephalography. Furthermore, these empathy-related neural activations were stronger in participants who reported stronger bodily self-attribution of the other person's hand. Our findings provide further evidence that empathy for pain engages sensorimotor resonance mechanisms. They also indicate that reducing bodily self-other distinction may increase such resonance for ingroup as well as outgroup targets.

Higher perceived stress is associated with lower cortisol concentrations but higher salivary interleukin-1beta in socially evaluated cold pressor test.

The relationship between subjective stress perception and the objective stress response to acute stress stimuli is not sufficiently understood. The aim of the present study was to test the hypothesis that the neuroendocrine response in socially evaluated cold pressor test (CPT) depends on the extent of perceived stressfulness of the stimulus. The test was performed in 24 healthy male volunteers. Subjective stress perception was assessed using nine visual analog scales. The subjects were divided to low and high stress perception groups according to the median split of the scores. Subjects with high stress perception exhibited slightly lower values of systolic blood pressure and lower overall concentrations of salivary cortisol compared to subjects with low stress perception. Salivary alpha-amylase activity did not show significant changes. Salivary aldosterone decreased in time in subjects with low but increased early after the test in subjects with high stress perception. Interestingly, salivary concentrations of the pro-inflammatory cytokine interleukin-1beta were considerably higher in subjects with high stress perception, particularly immediately before the test. The differences in salivary cortisol and interleukin-1beta were confirmed by the analysis with distress as a continuous covariate. Distress scores correlated negatively with salivary cortisol and positively with interleukin-1beta. The rate pressure product, which is a global measure of energy consumption by the heart, was significantly higher immediately before than after the stress exposure. The present findings show that concentrations of interleukin-1beta are a sensitive component of the stress response at the time before the stressful event.Lay summaryIt is generally expected that higher perceived stressfulness of a stimulus is accompanied by higher activation of stress-related systems. This study evaluating a combined psychosocial and physical stress situation in healthy men provides evidence that individual parameters of the stress response are differently related to perceived stress intensity. Subjects with high stress perception exhibited lower systolic blood pressure and salivary cortisol, higher interleukin-1beta, marginal differences in alpha amylase and aldosterone compared to subjects with low stress perception, which might be important for stress coping.

Dopamine concentrations and dopamine receptor gene expression in emotion-related brain structures of female adult rats exposed to stress of chronic isolation from weaning.

It is known that early-life stress events induce profound consequences on emotional brain regions including amygdala, involved in emotional processing and the ventral tegmental area (VTA), which contains neuron cell bodies of the mesolimbic dopaminergic system. The aim of this study is to test the hypothesis that stress induced by long-term social isolation from weaning in female rats is associated with alterations in amygdalar dopamine receptor gene expression and VTA dopamine concentrations. Rats were weaned on postnatal day 21 and then exposed to stress of chronic isolation for 9 weeks. Control animals were housed socially. Amygdalar dopamine D1 but not D2 receptor gene expression was decreased in isolated rats compared to controls. Dopamine concentrations in the VTA were enhanced following chronic isolation. A negative correlation was observed between amygdalar D1 gene expression and dopamine concentrations in the VTA. In conclusion, a reduction of dopamine D1 receptor gene expression in the amygdala in response to stress induced by chronic isolation in female rats was accompanied by an increase in dopamine concentration in the VTA. Further studies are needed to understand the physiological significance, if any, of negative association of amygdalar dopamine receptor D1 gene expression and dopamine concentrations in the VTA.

The Role of Sensorimotor Processes in Pain Empathy.

Pain is a salient, aversive sensation which motivates avoidance, but also has a strong social signaling function. Numerous studies have shown that regions of the nervous system active in association with first-hand pain are also active in response to the pain of others. When witnessing somatic pain, such as seeing bodies in painful situations, significant activations occur not only in areas related to the processing of negative emotions, but also in neuronal structures engaged in somatosensation and the control of skeletal muscles. These empathy-related sensorimotor activations are selectively reviewed in this article, with a focus on studies using electrophysiological methods and paradigms investigating responses to somatic pain. Convergent evidence from these studies shows that these activations (1) occur at multiple levels of the nervous system, from the spinal cord up to the cerebral cortex, (2) are best conceptualized as activations of a defensive system, in line with the role of pain to protect body from injury, and (3) contribute to establishing a matching of psychological states between the sufferer and the observer, which ultimately supports empathic understanding and motivate prosocial action. Future research should thus focus on how these sensorimotor responses are related to higher-order empathic responses, including affective sharing and emotion regulation, and how this motivates approach-related prosocial behaviors aimed at alleviating the pain and suffering of others.

Post-weaning social isolation of rats induces reduction in the gene expression of vascular endothelial growth factor (VEGF) in the hippocampus.

The role of vascular endothelial growth factor (VEGF) in chronic stress and neurodevelopmental disorders is of growing research interest. Here we show that post-weaning isolation rearing of rats decreased gene expression of VEGF in the hippocampus. Gene expression of VEGF upstream regulator fibroblast growth factor-2 (FGF-2) or its downstream mediator endothelial nitric oxide synthase (eNOS) was unchanged. Other signaling pathways appear to be involved in isolation-induced reduction in VEGF gene expression. Sex differences in VEGF and eNOS gene expression with significantly higher mRNA levels in females than males were revealed.

Remote associates test: An empirical proof of concept.

Associative processes play a major role in research on human thinking, especially creativity. One of the most influential models emphasizing associative processes in creative thinking was introduced by Mednick (Psychological Review, 69, 220-232, 1962), who developed the remote associates test (RAT) as a domain-general measure of individual differences in associative hierarchies. Although S. Mednick's theoretical framework has recently regained much attention, the fundamental psychometric assumptions and underlying cognitive processes involved in the RAT remain controversial. We carried out two studies to evaluate these issues. In the first, a confirmatory factor analysis showed that a single latent factor accounted for the ability to solve RAT problems, despite their psycholinguistic heterogeneity. Subsequent regression analyses indicated that cue-solution associative remoteness substantially determined the difficulty of RAT problems, accounting for about 80% of variance. In the second study we used a newly developed associative chain test (ACT), which assesses lexical-semantic and executive measures during associative processing. We found that performance on the RAT was related to lexical-semantic (higher response remoteness and lower response commonness) but not to executive (response inhibition and switching) ACT measures. Overall, our findings indicate that the RAT reflects a coherent ability to access and combine remote elements in lexical-semantic and associative networks without considerably engaging executive attention. Although the validity and utility of the RAT was supported, we propose that the ACT provides a more complex and fine-grained tool for the assessment of associative processing.

Association between genetic variability of neuronal nitric oxide synthase and sensorimotor gating in humans.

Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain.

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.

Links between brain cortical regions and EEG recording sites derived from forward modelling.

Electroencephalography (EEG) provides no direct link between electrode positions and underlying signal generators. Inferences based on spatial proximity between scalp positions and cortical structures are not reliable. More accurate source localization is obtained by solving both the forward and the inverse problem, but is technically challenging. In this paper, we provide a reference table of correspondence between EEG sensors and cortical anatomical regions based on a realistic head model. We also present a universal algorithm to compute the solution by using a forward model to determine the sensitivity for electrodes of any defined electrode positioning system and cortical anatomical parcellation.

Reduction of empathy for pain by placebo analgesia suggests functional equivalence of empathy and first-hand emotion experience.

Previous research in social neuroscience has consistently shown that empathy for pain recruits brain areas that are also activated during the first-hand experience of pain. This has been interpreted as evidence that empathy relies upon neural processes similar to those underpinning the first-hand experience of emotions. However, whether such overlapping neural activations imply that equivalent neural functions are engaged by empathy and direct emotion experiences remains to be demonstrated. We induced placebo analgesia, a phenomenon specifically modulating the first-hand experience of pain, to test whether this also reduces empathy for pain. Subjective and neural measures of pain and empathy for pain were collected using self-report and event-related potentials (ERPs) while participants underwent painful electrical stimulation or witnessed that another person was undergoing such stimulation. Self-report showed decreased empathy during placebo analgesia, and this was mirrored by reduced amplitudes of the pain-related P2, an ERP component indexing neural computations related to the affective-motivational component of pain. Moreover, these effects were specific for pain, as self-report and ERP measures of control conditions unrelated to pain were not affected by placebo analgesia. Together, the present results suggest that empathy seems to rely on neural processes that are (partially) functionally equivalent to those engaged by first-hand emotion experiences. Moreover, they imply that analgesics may have the unwanted side effect of reducing empathic resonance and concern for others.

Measuring semantic memory using associative and dissociative retrieval tasks.

Recent theoretical advances highlighted the need for novel means of assessing semantic cognition. Here, we introduce the associative-dissociative retrieval task (ADT), positing a novel way to test inhibitory control over semantic memory retrieval by contrasting the efficacy of associative (automatic) and dissociative (controlled) retrieval on a standard set of verbal stimuli. All ADT measures achieved excellent reliability, homogeneity, and short-term temporal stability. Moreover, in-depth stimulus level analyses showed that the associative retrieval is easier for words evoking few but strong associates, yet such propensity hampers the inhibition. Finally, we provided critical support for the construct validity of the ADT measures, demonstrating reliable correlations with domain-specific measures of semantic memory functioning (semantic fluency and associative combination) but negligible correlations with domain-general capacities (processing speed and working memory). Together, we show that ADT provides simple yet potent and psychometrically sound measures of semantic memory retrieval and offers noteworthy advantages over the currently available assessment methods.

Visual image retention does not contribute to modulation of event-related potentials by mental rotation.

Rotation of a visual image in mind is associated with a slow posterior negative deflection of the event-related potential (ERP), termed rotation-related negativity (RRN). Retention of a visual image in short-term memory is also associated with a slow posterior negative ERP, termed negative slow wave (NSW). We tested whether short-term memory retention, indexed by the NSW, contributes to the RRN. ERPs were recorded in the same subjects in two tasks, a mental rotation task, eliciting the RRN, and a visual short-term memory task, eliciting the NSW. Over both right and left parietal scalp, no association was found between the NSW and the RRN amplitudes. Furthermore, adjusting for the effect of the NSW had no influence on a significant association between the RRN amplitude and response time, an index of mental rotation performance. Our data indicate that the RRN reflects manipulation of a visual image but not its retention in short-term memory.