Task-switching preparation across semantic and spatial domains: An event-related potential study

Previous event-related potential (ERP) studies have identified the specific electrophysiological markers of advance preparation in cued task-switching paradigms. However, it is not yet completely clear whether there is a single task-independent preparatory mechanism for task-switching or whether preparation for a switch can be selectively influenced by the domain of the task to be performed. To address this question, we employed a cued-task switching paradigm requiring participants to repeat or to switch between a semantic and a spatial task. The behavioural results showed a significant switch cost for both domains. The ERP findings, however, revealed that switch and repeat trials for semantic and spatial domains differed in the amplitude modulation of an early P2 and a sustained negativity both expressed over fronto-central scalp regions. Further differences between the two domains also emerged over posterior-parietal electrodes. This pattern of data thus shows that advance preparation in task-switching can be selectively modulated by the domain of the task to be performed

TDCS over the right inferior frontal gyrus disrupts control of interference in memory: A retrieval-induced forgetting study

Retrieving information from episodic memory may result in later inaccessibility of related but taskirrelevant information. This phenomenon, known as retrieval-induced forgetting, is thought to represent a specific instance of broader cognitive control mechanisms, that would come into play during memory retrieval, whenever non-target competing memories interfere with recall of target items. Recent neuroimaging studies have shown an association between these mechanisms and the activity of the right Prefrontal Cortex. However, so far, few studies have attempted at establishing a causal relationship between this brain region and behavioural measures of cognitive control over memory. To address this missing link, we delivered transcranial Direct Current Stimulation (tDCS) over the right Inferior Frontal Gyrus (rIFG) during a standard retrieval-practice paradigm with category-exemplar word pairs. Across two experiments, tDCS abolished retrieval-induced forgetting to different degrees, compared to the sham control group whereas no effects of stimulation emerged in an ancillary measure of motor stopping ability. Moreover, influence analyses on specific subsets of the experimental material revealed diverging patterns of results, which depended upon the different categories employed in the retrieval-practice paradigm. Overall, the results support the view that rIFG has a causal role in the control of interference in memory retrieval and highlight the often underestimated role of stimulus material in affecting the effects. The present findings are therefore relevant in enriching our knowledge about memory functions from both a theoretical and methodological perspective

Human memory retrieval and inhibitory control in the brain: Beyond correlational evidence

Retrieving information from long-term memory can result in the episodic forgetting of related material. One influential account states that this retrieval-induced forgetting (RIF) phenomenon reflects inhibitory mechanisms called into play to decrease retrieval competition. Recent neuroimaging studies suggested that the prefrontal cortex, which is critically engaged in inhibitory processing, is also involved in retrieval competition situations. Here, we used transcranial direct current stimulation (tDCS) to address whether inhibitory processes could be causally linked to RIF. tDCS was administered over the right dorsolateral prefrontal cortex during the retrieval-practice phase in a standard retrieval-practice paradigm. Sixty human participants were randomly assigned to anodal, cathodal, or sham-control groups. The groups showed comparable benefits for practiced items. In contrast, unlike both the sham and anodal groups, the cathodal group exhibited no RIF. This pattern is interpreted as evidence for a causal role of inhibitory mechanisms in episodic retrieval and forgetting

Assessing the effects of tDCS over a delayed response inhibition task by targeting the right inferior frontal gyrus and right dorsolateral prefrontal cortex

Many situations in our everyday life call for a mechanism deputed to outright stop an ongoing course of action. This behavioral inhibition ability, known as response stopping, is often impaired in psychiatric conditions characterized by impulsivity and poor inhibitory control. Transcranial direct current stimulation (tDCS) has recently been proposed as a tool for modulating response stopping in such clinical populations, and previous studies in healthy humans have already shown that this noninvasive brain stimulation technique is effectively able to improve response stopping, as measured in a stop-signal task (SST) administered immediately after the stimulation. So far, the right inferior frontal gyrus (rIFG) has been the main focus of these attempts to modulate response stopping by the means of noninvasive brain stimulation. However, other cortical areas such as the right dorsolateral prefrontal cortex (rDLPFC) have been implicated in inhibitory control with other paradigms. In order to provide new insight about the involvement of these areas in response stopping, in the present study, tDCS was delivered to 115 healthy subjects, using five stimulation setups that differed in terms of target area (rIFG or rDLPFC) and polarity of stimulation (anodal, cathodal, or sham). The SST was performed 15 min after the offset of the stimulation. Consistently with previous studies, only anodal stimulation over rIFG induced a reliable, although weak, improvement in the SST, which was specific for response stopping, as it was not mirrored in more general reaction time measures

Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study

In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient\u2019s global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient.This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD

The Relation between Self-Reported Empathy and Motor Identification with Imagined Agents

Background:In a previous study, we found that when required to imagine another person performing an action, participants reported a higher correspondence between their own handedness and the hand used by the imagined person when the agent was seen from the back compared to when the agent was seen from the front. This result was explained as evidence of a greater involvement of motor areas in the back-view perspective, possibly indicating a greater proneness to put oneself in the agent's shoes in such a condition. In turn, the proneness to put oneself in another's shoes could also be considered as a cue of greater identification with the other, that is a form of empathy. If this is the case, the proportion of lateral matches vs mismatches should be different for subjects with high and low self-reported empathy. In the present study, we aimed at testing this hypothesis.Methodology/Principal Findings:Participants were required to imagine a person performing a single manual action in a back view and to indicate the hand used by the imagined person during movement execution. Consistent with our hypothesis, the proportion of matching between the handedness of participants and the handedness of agents imagined was higher for participants scoring high in a self-report measure of empathy. Importantly, this relationship was specific for females.Conclusions/Significance:At least for females, our data seem to corroborate the idea of a link between self-reported empathy and motor identification with imagined agents. This sex-specific result is consistent with neuroimaging studies indicating a stronger involvement of action representations during emotional and empathic processing in females than in males. In sum, our findings underline the possibility of employing behavioral research as a test-bed for theories deriving from functional studies suggesting a link between empathic processing and the activation of motor-related areas

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells.

The aim of this study was to investigate the role of an antichondrogenic factor, MIR221 (miR‐221), in intervertebral disc degeneration (IDD), and provide basic information for the development of a therapeutic strategy for the disc repair based on specific nucleic acid based drugs, such as miR‐221 silencing. We established a relatively quick protocol to minimize artifacts from extended in vitro culture, without selecting the different types of cells from intervertebral disc (IVD) or completely disrupting extracellular matrix (ECM), but by using the whole cell population with a part of resident ECM. During the de‐differentiation process miR‐221 expression significantly increased. We demonstrated the effectiveness of miR‐221 silencing in driving the cells towards chondrogenic lineage. AntagomiR‐221 treated cells showed in fact a significant increase of expression of typical chondrogenic markers including COL2A1, ACAN and SOX9, whose loss is associated with IDD. Moreover, antagomiR‐221 treatment restored FOXO3 expression and increased TRPS1 expression levels attenuating the severity grade of degeneration, and demonstrating in a context of tissue degeneration and inflammation not investigated before, that FOXO3 is target of miR‐221. Data of present study are promising in the definition of new molecules useful as potential intradiscal injectable biological agents

Pro‑differentiating compounds for human intervertebral disc cells are present in Violina pumpkin leaf extracts

The intervertebral disc degeneration (IDD) is closely associated with inflammation, oxidative stress and loss of the discogenic phenotype which current therapies are unable to reverse. Here, the effects of acetone extract from Violina pumpkin (Cucurbita moschata) leaves on degenerated intervertebral disc (IVD) cells was investigated. IVD cells were isolated from degenerated disc tissue of patients undergoing spinal surgery, and exposed to acetone extract and three major thin layer chromatography subfractions. We found that the cells benefit from exposure in particular to subfraction 7 consisting almost entirely of p-Coumaric acid. Subfraction 7-treated cells showed a significant increase of discogenic transcription factors (SOX9, TRPS1), extracellular matrix components (aggrecan, collagen type II), cellular homeostasis and stress response regulators (FOXO3a, Nrf2, SOD2, SIRT1). Migratory ability and the expression of OCT4, two important markers related to the presence and activity of stem cells also increased. Moreover, subfraction 7 counteractes H2O2-triggered cell damage preventing in particular the increase of the pro-inflammatory and antichondrogenic microRNA, miR-221. This strengthens the hypothesis that adequate stimuli can support resident cells to repopulate the degenerate IVD and restart the anabolic machinery. Taken together, the data we obtained contribute to the discovery of molecules potentially effective in slowing the progression of IDD, a disease for which there is currently no effective treatment. Moreover, the enhancement of a part of plant, the pumpkin leaves, considered a waste product in the Western world, demonstrating that it contains substances with potential beneficial effects on human health

Asymmetric Cortical Adaptation Effects during Alternating Auditory Stimulation

The present study investigates hemispheric asymmetries in the neural adaptation processes occurring during alternating auditory stimulation. Stimuli were two monaural pure tones having a frequency of 400 or 800 Hz and a duration of 500 ms. Electroencephalogram (EEG) was recorded from 14 volunteers during the presentation of the following stimulus sequences, lasting 12 s each: 1) evoked potentials (EP condition, control), 2) alternation of frequency and ear (FE condition), 3) alternation of frequency (F condition), and 4) alternation of ear (E condition). Main results showed that in the central area of the left hemisphere (around C3 site) the N100 response underwent adaptation in all patterns of alternation, whereas in the same area of the right hemisphere the tones presented at the right ear in the FE produced no adaptation. Moreover, the responses to right-ear stimuli showed a difference between hemispheres in the E condition, which produced less adaptation in the left hemisphere. These effects are discussed in terms of lateral symmetry as a product of hemispheric, pathway and ear asymmetries

SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts

<p>Abstract</p> <p>Background</p> <p>Lymphoid Enhancer Factor-1 (Lef-1) is a member of a transcription factor family that acts as downstream mediator of the Wnt/β-catenin signalling pathway which plays a critical role in osteoblast proliferation and differentiation. In a search for Lef-1 responsive genes in human osteoblasts, we focused on the transcriptional regulation of the SLUG, a zinc finger transcription factor belonging to the Snail family of developmental proteins. Although the role of SLUG in epithelial-mesenchymal transition and cell motility during embryogenesis is well documented, the functions of this factor in most normal adult human tissues are largely unknown. In this study we investigated SLUG expression in normal human osteoblasts and their mesenchymal precursors, and its possible correlation with Lef-1 and Wnt/β-catenin signalling.</p> <p>Results</p> <p>The experiments were performed on normal human primary osteoblasts obtained from bone fragments, cultured in osteogenic conditions in presence of Lef-1 expression vector or GSK-3β inhibitor, SB216763. We demonstrated that the transcription factor SLUG is present in osteoblasts as well as in their mesenchymal precursors obtained from Wharton's Jelly of human umbilical cord and induced to osteoblastic differentiation. We found that SLUG is positively correlated with RUNX2 expression and deposition of mineralized matrix, and is regulated by Lef-1 and β-catenin. Consistently, Chromatin Immunoprecipitation (ChIP) assay, used to detect the direct Lef/Tcf factors that are responsible for the promoter activity of SLUG gene, demonstrated that Lef-1, TCF-1 and TCF4 are recruited to the SLUG gene promoter "<it>in vivo</it>".</p> <p>Conclusion</p> <p>These studies provide, for the first time, the evidence that SLUG expression is correlated with osteogenic commitment, and is positively regulated by Lef-1 signal in normal human osteoblasts. These findings will help to further understand the regulation of the human SLUG gene and reveal the biological functions of SLUG in the context of bone tissue.</p