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.

Electrical stimulation of the cerebellum facilitates automatic but not controlled word retrieval.

Recent research has indicated that the cerebellum is engaged in language functions, yet the role of the cerebellum in lexical-semantic memory is poorly understood. In a double-blind randomized controlled experiment, we therefore targeted the cerebellum by transcranial direct current stimulation (tDCS) to assess and compare the contribution of the cerebellar processing to automatic and controlled retrieval of words in healthy adults (n = 136). Anodal cerebellar tDCS facilitated retrieval of semantically related words in free-associative chains, which was not due to a non-specific acceleration of processing speed. The stimulation had no influence on controlled word retrieval that employed inhibition or switching. The effect of cathodal tDCS was opposite to the anodal stimulation, but statistically non-significant. Our data show that the cerebellum is engaged extracting associative information from the system of semantic representations, established and strengthened/automated by learning, and indicates a domain-general role of this structure in automation of behavior, cognition and language.

Fear of heights shapes postural responses to vibration-induced balance perturbation at virtual height.

Introduction: Standing upright at height is a challenging situation involving intense threat of balance loss and fall. The ability to maintain balance in such conditions requires properly resolving sensory conflicts and is influenced by fear. To get more insight on the role of fear in balance control at height, we explored the dynamics of postural behavior in the situation of enhanced threat of potential balance loss. Methods: In 40 young individuals with varying fear of heights, we combined simulated exposure to height in a virtual reality environment with bilateral vibration of tibialis anterior muscles which evokes posture destabilization (the so-called vibration-induced falling). Results: Under such condition of enhanced postural threat, individuals with intense fear of heights showed stronger stiffening of posture compared with individuals with low fear of heights who react more flexibly and adaptively to posture destabilization. This group difference was evident already at ground level but further increased during virtual height exposure. Discussion: Our data show that fear of height significantly affects posture adaptation to balance-destabilizing events. Our findings demonstrate that the assessment of postural behavior during threatening situations in the virtual reality environment provides valuable insights into the mechanisms of balance control and may be used to develop novel strategies aimed at prevention of falls.

BDNF Val66Met polymorphism is associated with consolidation of episodic memory during sleep.

The brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, a candidate neurobiological mechanism underlying learning and memory. A functional polymorphism in the BDNF gene, Val66Met (rs6265), has been linked to memory and cognition in healthy individuals and clinical populations. Sleep contributes to memory consolidation, yet information about the possible role of BDNF in this process is scarce. To address this question, we investigated the relationship between the BDNF Val66Met genotype and consolidation of episodic declarative and procedural (motor) non-declarative memories in healthy adults. The carriers of Met66 allele, as compared with Val66 homozygotes, showed stronger forgetting overnight (24 h after encoding), but not over shorter time (immediately or 20 min after word list presentation). There was no effect of Val66Met genotype on motor learning. These data suggest that BDNF plays a role in neuroplasticity underlying episodic memory consolidation during sleep.

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.

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.

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.

Assessment of Automatic and Controlled Retrieval Using Verbal Fluency Tasks.

Category and letter verbal fluency assessment is widely used in basic and clinical research. Yet, the nature of the processes measured by such means remains a matter of debate. To delineate automatic (free-associative) versus controlled (dissociative) retrieval processes involved in verbal fluency tasks, we carried out a psychometric study combining a novel lexical-semantic retrieval paradigm and structural equation modeling. We show that category fluency primarily engages a free-associative retrieval, whereas letter fluency exerts executive suppression of habitual semantic associates. Importantly, the models demonstrated that this dissociation is parametric rather than absolute, exhibiting a degree of unity as well as diversity among the retrieval measures. These findings and further exploratory analyses validate that category and letter fluency tasks reflect partially distinct forms of memory search and retrieval control, warranting different application in basic research and clinical assessment. Finally, we conclude that the novel associative-dissociative paradigm provides straightforward and useful behavioral measures for the assessment and differentiation of automatic versus controlled retrieval ability.

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.

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.

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 left prefrontal cortex supports inhibitory processing during semantic memory retrieval.

Semantic control refers to a set of neural and cognitive mechanisms that govern semantic processing and retrieval. Neuroimaging studies have indicated that controlled semantic processing engages the left prefrontal cortex (PFC), yet the functional role of the prefrontal activity in semantic control is poorly understood and was therefore addressed in the present study. We used a double-blind randomized controlled experiment, in which participants from three distinct groups received anodal transcranial direct current stimulation (tDCS) over left lateral PFC (n = 40), a control tDCS over temporoparietal cortex (n = 40), or sham stimulation (n = 41), while executing automatic and controlled semantic retrieval tasks as well as additional control tasks assessing working memory and semantic judgement. We demonstrate that anodal tDCS of the left lateral PFC improved inhibition of prepotent semantic associations but had no significant effect on retrieval of habitual associates or switching between retrieval rules. The prefrontal tDCS also enhanced working memory capacity, but this effect did not account for the improved semantic inhibition. The control temporoparietal tDCS did not affect semantic retrieval. Our findings show that semantic inhibition and switching represent distinct components of the semantic control system and indicate that the left lateral PFC is involved in a filtering process that constrains the accessible semantic representations (i.e., a proactive pre-retrieval inhibition) or suppresses already retrieved responses (i.e., a retroactive post-retrieval inhibition). The recognition of such an inhibitory process could inspire novel treatments targeting altered semantic processing.

The Effects of Virtual Height Exposure on Postural Control and Psychophysiological Stress Are Moderated by Individual Height Intolerance.

Virtual reality (VR) enables individuals to be exposed to naturalistic environments in laboratory settings, offering new possibilities for research in human neuroscience and treatment of mental disorders. We used VR to study psychological, autonomic and postural reactions to heights in individuals with varying intensity of fear of heights. Study participants (N = 42) were immersed in a VR of an unprotected open-air elevator platform in an urban area, while standing on an unstable ground. Virtual elevation of the platform (up to 40 m above the ground level) elicited robust and reliable psychophysiological activation including increased distress, heart rate, and electrodermal activity, which was higher in individuals suffering from fear of heights. In these individuals, compared with individuals with low fear of heights, the VR height exposure resulted in higher velocity of postural movements as well as decreased low-frequency (<0.5 Hz) and increased high-frequency (>1 Hz) body sway oscillations. This indicates that individuals with strong fear of heights react to heights with maladaptive rigidity of posture due to increased weight of visual input for balance control, while the visual information is less reliable at heights. Our findings show that exposure to height in a naturalistic VR environment elicits a complex reaction involving correlated changes of the emotional state, autonomic activity, and postural balance, which are exaggerated in individuals with fear of heights.

Genetic Determinants of Gating Functions: Do We Get Closer to Understanding Schizophrenia Etiopathogenesis?

Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition-CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression-CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms (HTR2A rs6311 and TCF4 rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field.

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 effects of testosterone on the physiological response to social and somatic stressors.

Higher testosterone levels in males have previously been linked to decreased stress reactivity, but in other cases, testosterone has been reported to increase the stress response. We addressed these inconsistencies in a placebo-controlled single-dose testosterone administration study, in which 120 male participants were randomly assigned to undergo a cold-pressor test (CPT, a non-social somatic stressor), a socially evaluated cold-pressor test (SECPT, a social-somatic stressor), or a lukewarm water test (LWT, a non-stressful control condition). Throughout the experiment, blood pressure and interbeat intervals were measured continuously, and saliva samples for hormonal analyses were taken repeatedly at predefined time points. When comparing the groups treated with placebo, the SECPT elicited a larger increase in the systolic blood pressure than CPT, in agreement with previous studies. However, testosterone administration altered this pattern. Compared to placebo, testosterone increased systolic blood pressure during the CPT, whereas the opposite effect was found during the SECPT. Cortisol reactivity was not affected by testosterone administration. The CAG repeat polymorphism of the androgen receptor gene was unrelated to the effects of testosterone on the stress response, but it was correlated with blood pressure across the whole sample. Our findings demonstrate that testosterone's effects on the stress response are dependent on the social context. Testosterone's ability to flexibly influence the response to stressors may be an important mechanism through which the hormone promotes adaptive behavior. Our results are also in line with research showing that testosterone decreases social anxiety and suggest it may help to modulate the effects of stress in socially challenging situations.

Left Prefrontal Cortex Supports the Recognition of Meaningful Patterns in Ambiguous Stimuli.

Processing of ambiguous visual stimuli has been associated with an increased activation of the left lateral prefrontal cortex (PFC) in neuroimaging studies. Nevertheless, the functional role of prefrontal activity in this process is not fully understood. In this experiment we asked participants to evaluate ambiguous inkblots from the Rorschach test, while stimulating the left lateral PFC using excitatory anodal transcranial direct current stimulation (tDCS). In addition, visual insight ability was assessed as a control measure requiring visual and conceptual restructuring and convergent thinking rather than divergent idea generation employed to interpret the equivocal Rorschach inkblots. Using a randomized double-blind design, we demonstrated that anodal tDCS increased the number of meaningful patterns recognized in the inkblots but had no significant effect on visual insight. These findings support the role of left lateral PFC in the processing of ambiguous visual information and object recognition. More generally, we discuss that the PFC may be involved in the mechanisms supporting the activation of stored visual and semantic representations in order to compensate for less informative bottom-up inputs and thus facilitate flexible cognition and idea generation.

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.