Exogenous Cues Research Articles

A Functional Connection between the Circadian Clock and Hormonal Timing in Arabidopsis.

The rotation of the Earth entails changes in environmental conditions that pervasively influence an organism’s physiology and metabolism. An internal cellular mechanism known as the circadian clock acts as an internal timekeeper that is able to perceive the changes in environmental cues to generate 24-h rhythms in synchronization with daily and seasonal fluctuations. In plants, the circadian clock function is particularly important and regulates nearly every aspect of plant growth and development as well as proper responses to stresses. The circadian clock does not function in isolation but rather interconnects with an intricate network of different pathways, including those of phytohormones. Here, we describe the interplay of the circadian clock with a subset of hormones in Arabidopsis. The molecular components directly connecting the circadian and hormone pathways are described, highlighting the biological significance of such connections in the control of growth, development, fitness, and survival. We focus on the overlapping as well as contrasting circadian and hormonal functions that together provide a glimpse on how the Arabidopsis circadian system regulates hormone function in response to endogenous and exogenous cues. Examples of feedback regulation from hormone signaling to the clock are also discussed.

Local Auxin Biosynthesis Mediates Plant Growth and Development.

Auxin is one of the most important plant hormones controlling various aspects of plant growth and development. Here, we highlight three recent papers that shed light on how local auxin biosynthesis contributes to plant growth and development in response to endogenous developmental signals and exogenous environmental cues, such as shade and aluminum stress.

Differential effects of vestibular processing on orienting exogenous and endogenous covert visual attention.

Recent research highlights the overwhelming role of vestibular information for higher order cognition. Central to body perception, vestibular cues provide information about self-location in space, self-motion versus object motion, and modulate the perception of space. Surprisingly, however, little research has dealt with how vestibular information combines with other senses to orient one's attention in space. Here we used passive whole body rotations as exogenous (Experiment 1) or endogenous (Experiment 2) attentional cues and studied their effects on orienting visual attention in a classical Posner paradigm. We show that-when employed as an exogenous stimulus-rotation impacts attention orienting only immediately after vestibular stimulation onset. However, when acting as an endogenous stimulus, vestibular stimulation provides a robust benefit to target detection throughout the rotation profile. Our data also demonstrate that vestibular stimulation boosts attentional processing more generally, independent of rotation direction, associated with a general improvement in performance. These data provide evidence for distinct effects of vestibular processing on endogenous and exogenous attention as well as alertness that differ with respect to the temporal dynamics of the motion profile. These data reveal that attentional spatial processing and spatial body perception as manipulated through vestibular stimulation share important brain mechanisms.

Modulation of circadian rhythms through estrogen receptor signaling.

Circadian rhythms are physiological and behavioral processes that exhibit a 24-hr cycle. These daily rhythms are essential for living organisms to align their behavior and physiology with the environment to increase the likelihood of survival. In mammals, circadian rhythms synchronize with the environment primarily by the suprachiasmatic nucleus, a hypothalamic brain region that integrates exogenous and endogenous timing cues. Sex steroid hormones, including estrogens, are thought to modulate sexually dimorphic behaviors through developmental programming of the brain (i.e., organization), as well as acute receptor signaling during adulthood (i.e., activation). Importantly, there are known sex differences in the expression of circadian locomotor activity and molecular organization of the suprachiasmatic nucleus, likely due, in part, to the actions of circulating estrogens. Circadian locomotor rhythms, which are coordinated by the suprachiasmatic nucleus, have been shown to be regulated by developmental and adult levels of circulating estrogens. Further, increasing evidence suggests that estrogens can modulate expression of circadian clock genes that are essential for orchestration of circadian rhythms by the suprachiasmatic nucleus. In this review, we will discuss the organizational and activational modulation of the circadian timekeeping system by estrogens through estrogen receptor signaling.

The neglected contribution of memory encoding in spatial cueing: A new theory of costs and benefits.

Spatial cueing is thought to indicate the resource limits of visual attention because invalidly cued items are reported more slowly and less accurately than validly cued items. However, limited resource accounts cannot explain certain findings, such as dividing attention without costs, or attentional benefits without invalidity costs. The current study presents a new account of exogenous cueing, namely the memory encoding cost (MEC) theory, which integrates attention and memory encoding to explain costs and benefits evoked by a spatial cue. Unlike conventional theories that focus on the role of attention in yielding spatial cueing effects, the MEC theory argues that some cueing effects are caused by a combination of attentional facilitation evoked by the cue, but also the cost of encoding the cue into memory. The crucial implication of this theory is that limitations in attentional deployment may not necessarily be the cause of invalidity costs. MEC generates a number of predictions that we test here, providing five convergent lines of evidence that cue encoding plays a key role in producing cueing effects. Furthermore, the MEC suggests a common mechanism underlying cueing costs and the attentional blink, and we simulate the core empirical findings of the current study with an existing attentional blink model. The model was able to simulate these effects primarily through manipulation of a single parameter that corresponds to memory encoding. The MEC theory thus simplifies our theoretical understanding of attentional effects by linking the attentional blink and some varieties of spatial cueing costs to a common mechanism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of Exogenous Auditory Attention on Temporal and Spectral Resolution.

Previous research in the visual domain suggests that exogenous attention in form of peripheral cueing increases spatial but lowers temporal resolution. It is unclear whether this effect transfers to other sensory modalities. Here, we tested the effects of exogenous attention on temporal and spectral resolution in the auditory domain. Eighteen young, normal-hearing adults were tested in both gap and frequency change detection tasks with exogenous cuing. Benefits of valid cuing were only present in the gap detection task while costs of invalid cuing were observed in both tasks. Our results suggest that exogenous attention in the auditory system improves temporal resolution without compromising spectral resolution.

Adaptive Cueing Treatment of Neglect in Stroke Patients Leads to Improvements in Activities of Daily Living: A Randomized Controlled, Crossover Trial

Background. Visuospatial neglect is a disabling syndrome with serious consequences for activities in daily life. This study investigated the effect of adaptive cueing during a reading task as a possible treatment for neglect by including (1) a task relevant for the patient’s daily life, (2) a fading out procedure to stimulate independent orientation to the left by self-cueing, and (3) a clear definition of neglect severity for the adaptive treatment protocol. Methods. A randomized controlled crossover design was used, including 26 patients from an early rehabilitation unit with left-sided visuospatial neglect after stroke or hemorrhage. They were examined twice at baseline (T1, T2), after 15 daily sessions in 1 condition (T3), and again after 15 daily sessions in the other condition (T4). The intervention condition included a daily reading task combined with endogenous and exogenous cues provided by a therapist, which were continuously reduced after a patient had reached a defined level of performance. The control condition consisted of a neuropsychological treatment of the same length, not targeting visuospatial attention. Results. Significant improvements were shown after intervention on scores for reading (word and text reading), daily life activities (Catherine Bergego Scale), Line Bisection, and the Clock Drawing Task. Conclusion. This study shows that adaptive cueing in a reading task can improve neglect symptoms by using an intensive intervention lasting 3 weeks.

Exploring microRNA profiles for circadian clock and flowering development regulation in Himalayan Rhododendron

miRNA is a non-coding, yet crucial entity in remodeling the genetic architecture. Rhododendron arboreum of Himalayas grows and even flower under fluctuating climate. sRNA from leaves of vegetative and reproductive periods was sequenced to elucidate its seasonal associations. Conserved (256) and novel (210) miRNAs and their precursors were located based on homology with plant databases and transcriptome of the species. 27,139 predicted targets were involved with metabolism, reproduction, and response to abiotic stimuli. A comparative analysis showed differential expression of 198 miRNAs with season-specific abundance of 103 miRNAs. Specific isoforms of 11 miRNA families exhibited a temporal expression and targeted different genes implying a complex regulation. The variable miRNA expression among the tissues of different conditions can be associated with the adaptability of the species, which will prove essential for further study on miRNAs mediating seasonal response. Moreover, exogenous cues also mediate phase transition via networking of flowering pathways and their components. In this context, 18 known families and 77 novel miRNAs modulating 117 genes crucial in circadian entrainment were filtered. A negative correlation was obtained between the expression of 18 of these miRNAs and their targets when tested through quantitative-PCR. It highlighted the role of miRNA-target pairs in perceiving environmental variabilities and monitoring flowering growth. Furthermore, a phylogenetic clustering was performed, which supported the lineage-specific evolution and function of putative miR156 sequence in the species. This documentation of genome-wide profiling of miRNA, their targets, and expression will enhance the understanding of developmental and climate-tolerance strategies in high-altitude trees.

Cue predictability does not modulate bottom-up attentional capture.

Attention can be involuntarily captured by physically salient stimuli, a phenomenon known as bottom-up attention. Typically, these salient stimuli occur unpredictably in time and space. Therefore, in a series of three behavioural experiments, we investigated the extent to which such bottom-up attentional capture is a function of one's prior expectations. In the context of an exogenous cueing task, we systematically manipulated participants' spatial (Experiment 1) or temporal (Experiments 2 and 3) expectations about an uninformative cue and examined the amount of attentional capture by the cue. We anticipated larger attentional capture for unexpected compared to expected cues. However, while we observed attentional capture, we did not find any evidence for a modulation of attentional capture by prior expectation. This suggests that bottom-up attentional capture does not appear modulated by the degree to which the cue is expected or surprising.

No supplementary evidence of attention to a spatial cue when saccadic facilitation is absent

Attending a location in space facilitates responses to targets at that location when the time between cue and target is short. Certain types of exogenous cues – such as sudden peripheral onsets – have been described as reflexive and automatic. Recent studies however, have been showing many cases where exogenous cues are less automatic than previously believed and do not always result in facilitation. A lack of the behavioral facilitation, however, does not automatically necessitate a lack of underlying attention to that location. We test exogenous cueing in two experiments where facilitation is and is not likely to be observed with saccadic responses. We also test alternate measures linked to the allocation of attention such as saccadic curvature, microsaccades and pupil size. As expected, we find early facilitation as measured by saccadic reaction time when CTOAs are predictable but not when they are randomized within a block. We find no impact of the cue on microsaccade direction for either experiment, and only a slight dip in the frequency of microsaccades after the cue. We do find that change in pupil size to the cue predicts the magnitude of the validity effect, but only in the experiment where facilitation was observed. In both experiments, we observed a tendency for saccadic curvature to deviate away from the cued location and this was stronger for early CTOAs and toward vertical targets. Overall, we find that only change in pupil size is consistent with observed facilitation. Saccadic curvature is influenced by the onset of the cue, buts its direction is indicative of oculomotor inhibition whether we see RT facilitation or not. Microsaccades were not diagnostic in either experiment. Finally, we see little to no evidence of attention at the cued location in any additional measures when facilitation of saccadic responses is absent.

Contrasting effects of exogenous cueing on saccades and reaches.

Previous studies have shown that eye and arm movements tend to be intrinsically coupled in their behavior. There is, however, no consensus on whether planning of eye and arm movements is based on shared or independent representations. One way to gain insight into these processes is to compare how exogenous attentional modulation influences the temporal and spatial characteristics of the eye and the arm during single or combined movements. Thirteen participants (M = 22.8 years old, SD = 1.5) performed single or combined movements to an eccentric target. A behaviorally irrelevant cue flashed just before the target at different locations. There was no effect of the cue on the saccade or reach amplitudes, whether they were performed alone or together. We found no differences in overall reaction times (RTs) between single and combined movements. With respect to the effect of the cue, both saccades and reaches followed a similar pattern with the shortest RTs when the cue was closest to the target, which we propose reflects effector-independent processes. Compared to when no cue was presented before the target, saccade RTs were generally inhibited by the irrelevant cue with increasing cue-target distance. In contrast, reach RTs showed strong facilitation at the target location and less facilitation at farther distances. We propose that this reflects the presence of effector-dependent processes. The similarities and differences in RTs between the saccades and reaches are consistent with effector-dependent and -independent processes working in parallel.

Attentional modulation of speed-change perception in the perifoveal and near-peripheral visual field.

The ability to perceive changes in motion, such as rapid changes of speed, has important ecological significance. We show that exogenous and endogenous attention have different effects on speed-change perception and operate differently in different regions of the visual field. Using a spatial-cueing paradigm, with either exogenous or endogenous cues followed by drifting Gabor patches of changing speed that appear at the cued or uncued location, we measured participants’ thresholds for localizing both acceleration and deceleration of the Gabor patches in different regions (5° and 10°) of the visual field. The results revealed a larger exogenous cueing effect, indexed by a lower threshold for the cued relative to the uncued conditions, at 5° for perceiving acceleration and at 10° for perceiving deceleration. Endogenous attention, in contrast, improved performance equally at both eccentricities. We conclude that exogenous and endogenous spatial orienting constitute two independent attentional systems, with distinct modulation patterns on speed change perception in the visual field. While exogenous attentional modulation is eccentricity-dependent, endogenous attention acts homogeneously in perifoveal and near-peripheral regions of the visual field.

Using Mental Imagery to Manipulate the Future Time Perspective of Young Adults: Effects on Attentional Bias in Relation to Depressive Tendencies

Socioemotional selectivity theory postulates that a person with an expansive future time perspective adopts positive and negative information equally to prepare for future events, whereas a person with a limited future time perspective favors selecting positive over negative information, which suggests an information processing bias. Therefore, the present study was conducted to examine both whether future mental imagery can affect future time perspectives and whether attentional biases can be observed under manipulated future time perspective conditions. To control for depressive tendencies, which was assumed to affect the examination of attentional bias, 24 college students with high depressive tendencies [6 men, 18 women; mean age 18.46 years, standard deviation (SD) = 0.66] and 22 with low depressive tendencies (7 men, 15 women; mean age = 18.73 years, SD = 1.12) were recruited as participants and instructed to generate mental imagery about the long-term (short-term) future in order to achieve a limited (expansive) future time perspective condition. Attentional bias was then examined using an exogenous cueing task with long cue presentations. The effectiveness of the manipulation method used in this study was confirmed, and the results of the effects on attentional biases were analyzed. A significant difference in the difficulty of attentional disengagement from negative stimuli was observed among the participants with high depressive tendencies under the expansive future time perspective condition.

Role of mTOR Signaling in Tumor Microenvironment: An Overview.

The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy.

Attentional avoidance of emotional information in emotional eating

We investigated an attention bias (AB) for emotional faces in emotional eating (EM). A group obtaining a low score (n = 18) on the Emotional eating scale of the Dutch Eating Behavior Questionnaire and a high scoring group (n = 23) completed the Exogenous Cueing Task (ECT). The ECT experiment measured their reaction times to the location of a target dot preceded by a happy, sad, angry or neutral face cue. The Coping Inventory for Stressful Situations was administrated to collect information on participants’ coping strategies. Compared to the group with a low degree of EM, the high EM group showed significant attentional avoidance of emotional faces, particularly negative faces, in the ECT. The coping questionnaire indicated that the high EM group displayed higher levels of avoidance coping compared to the low EM group. General levels of EM and avoidance coping were also positively correlated, and avoidance coping significantly predicted the level of EM. The findings of the present study indicate that attentional avoidance of emotional content, which has previously been observed in clinical studies of eating disorders (Cardi et al., 2015a; Davies et al., 2011), is also present in subclinical samples of EM.

Hand Position and Response Assignment Modulate the Activation of the Valence-Space Conceptual Metaphor.

Conceptual metaphor is ubiquitous in language and thought, as we usually reason and talk about abstract concepts in terms of more concrete ones via metaphorical mappings that are hypothesized to arise from our embodied experience. One pervasive example is the conceptual projection of valence onto space, which flexibly recruits the vertical and lateral spatial frames to gain structure (e.g., good is up-bad is down and good is right-bad is left). In the current study, we used a valence judgment task to explore the role that exogenous bodily cues (namely response hand positions) play in the allocation of spatial attention and the modulation of conceptual congruency effects. Experiment 1 showed that congruency effects along the vertical axis are weakened when task conditions (i.e., the use of vertical visual cues, on the one hand, and the horizontal alignment of responses, on the other) draw attention to both the vertical and lateral axes making them simultaneously salient. Experiment 2 evidenced that the vertical alignment of participants' hands while responding to the task-regardless of the location of their dominant hand-facilitates the judgment of positive and negative-valence words, as long as participants respond in a metaphor-congruent manner (i.e., up responses are good and down responses are bad). Overall, these results support the claim that source domain representations are dynamically activated in response to the context and that bodily states are an integral part of that context.

P17. Impaired auditory attention in adolescents with developmental dyslexia

Theoretical background Developmental dyslexia (DD) refers to the pathological impairment in the acquisition of reading and/or writing skills that is not accounted for by biological age, intelligence or inadequate schooling (WHO, 2011). It is hypothesized that DD relies, at least in part, on the impaired ability to shift attention to relevant information (Hari and Renvall, 2001). On a neurophysiological level, attention is represented by alpha oscillations (about 8–12 Hz). In adults with DD, recent studies showed altered alpha oscillations during the processing of auditory and visual stimuli (Dhar et al., 2010) but also in resting state (Papagiannopoulou and Lagopoulos, 2016). However, until today, there is only sparse knowledge on auditory attention and the underlying neural mechanisms in adolescents with DD. Methods A sample of adolescents with diagnosed DD (Mean age: 14.29 years, SD: 1.46) and an age-matched control group (CG) participated in this study. In balanced order they performed two auditory spatial-cueing paradigms. In the exogenous paradigm, cue and target tones were presented monaurally at Stimulus onset Asynchrony (SOA) 100 ms and 250 ms. 50% of the trials consisted of valid cues. Catch trials (cue only) were intermittently presented. Participants had to respond as fast as possible whenever a target tone was presented. In the endogenous paradigm, cue and target tones were presented at SOAs between 1000 ms and 1500 ms. 80% of the trials consisted of valid cues. During both tasks EEG data was continuously recorded. Results While the CG showed an inhibition of return (IOR) i.e. reduced RT at invalid compared to valid cues with SOA 250 ms, no such effect was present in the DD sample. ERPs measured at the vertex electrode revealed prolonged peak latencies for target stimuli for both valid and invalid trials at SOA 250 ms in DD compared to CG. In the endogenous task, we found increased alpha desynchronization in the post-cue phase over left auditory cortex (AC) regions in DD compared to CG. Notably, this pattern was found irrespective of the site at which the cue was presented. Discussion The lack of an IOR in adolescents with DD demonstrates a decreased withdrawal of attention and suggests reduced orienting towards novel locations. Considering the endogenous task, our findings indicate a maladaptive inhibition of the left AC in DD that, in turn, might account for dysfunctional processing of incoming acoustic information. Our findings suggest altered auditory attention as potential basis for higher order language skills. Future studies investigating attention processes in pre-reading children will shed more light on whether attention is a cause of impaired language skills rather than the consequence of a maladaptive compensation over the course of reading/ writing acquisition.

External modulation of the sustained attention network in traumatic brain injury.

Traumatic brain injury (TBI) is associated with impairments in processing speed as well as higher-level cognitive functions that depend on distributed neural networks, such as regulating and sustaining attention. Although exogenous alerting cues have been shown to support patients in sustaining attentive, goal-directed behavior, the neural correlates of this rehabilitative effect are unclear. The purpose of this study was to explore the effects of moderate to severe TBI on activity and functional connectivity in the well-documented right-lateralized frontal-subcortical-parietal sustained attention network, and to assess the effects of alerting cues. Using multivariate analysis of fMRI data, TBI patients and matched neurologically healthy (NH) comparison participants were scanned as they performed the Sustained Attention to Response Task (SART) in 60-s blocks, with or without exogenous cueing through brief auditory alerting tones. Results documented inefficient voluntary control of attention in the TBI patients, with reduced functional connectivity in the sustained attention network relative to NH participants. When alerting cues were present during the SART, however, functional connectivity increased and became comparable to activity patterns seen in the NH group. These findings provide novel evidence of a neural mechanism for the facilitatory effects of alerting cues on goal-directed behavior in patients with damaged attentional brain systems, and support their use in cognitive rehabilitation. (PsycINFO Database Record

PO-389 Epigenomic and mutation determinants of carcinogen-driven primary epithelial cell immortalization

IntroductionBased on cancer genome sequencing, almost 600 genes have been implicated in cancer development to date, and recently, chromatin structural changes have emerged as a key mechanism for translating exogenous cues, such as carcinogen exposures, to the deregulation of biological processes implicated in tumorigenesis. However, the functional relationship between genetic and epigenetic alterations in the context of early events of carcinogen-driven cell transformation is not well understood.Material and methodsWe employ an in vitro carcinogen exposure system using primary human mammary epithelial cells (HMEC), which utilises a biological barrier bypass to mimic early steps of cell transformation, to introduce genetic and epigenetic alterations and to investigate their functional interplay during cell immortalization. A temporal, integrated (epi)genomic analysis is applied to benzo[a]pyrene (B[a]P)-exposed, immortalised HMEC, involving whole genome sequencing (WGS), analyses of chromatin structure (ChIP-seq, ATAC-seq), and patterns of gene regulation (DNA methylome 850K array, RNA-seq).Results and discussionsWGS of sequentially derived post-stasis and immortalised clones, as well as tumorigenic clones (generated by TP53 insertional mutagenesis of post-stasis lines), identified a prominent B[a]P mutational signature across all clones. While all sequenced clones had comparable SBS counts, we observed a gradual increase of structural variants, most notably copy number variations, from post-stasis to immortal and tumorigenic clones. Reproducibly distinct methylome patterns also correlated closely with the individual phenotypic stages of cell transformation. Chromatin accessibility analysis further showed changes characteristic to individual as well as multiple exposed clones, such as in the breast cancer tumour suppressor gene BRCA2 or the promoter region of PCDH18, a gene frequently inactivated by promoter methylation in colorectal cancer. Cell type-matched histone modification and RNA expression patterns are being established to enable a thorough integrated analysis of genetic and epigenetic determinants of carcinogen-driven HMEC transformation.ConclusionWe propose that in-depth, integrated (epi)genomic analysis of this innovative model system can reveal novel molecular determinants of carcinogen-driven cellular immortalization, thus improving our understanding of cancer causes, development and progression.Funding INCa-INSERM Plan Cancer 2015 Grant.

Transcriptomic and functional analyses unveil the role of long non-coding RNAs in anthocyanin biosynthesis during sea buckthorn fruit ripening

Fruit ripening is a developmental process regulated by a complex network of endogenous and exogenous cues. Sea buckthorn is an excellent material for fruit ripening studies due to its dramatic ripening process and high contents of nutritional and anti-oxidant compounds in berries. Here, the whole transcriptome of sea buckthorn fruit at three development stages were analysed using multiple high-throughput sequencings. We assembled and annotated 9,008 long non-coding RNAs (lncRNAs) in sea buckthorn fruits, and identified 118 differentially expressed lncRNAs (DE-lncRNAs) and 32 differentially expressed microRNAs in fruit developmental process. In addition, we predicted 1,061 cis-regulated and 782 trans-regulated targets of DE-lncRNAs, and these DE-lncRNAs are specifically enriched in the biosynthesis of ascorbic acid, carotenoids and flavonoids. Moreover, the silencing of two lncRNAs (LNC1 and LNC2) in vivo and expression analysis revealed that LNC1 and LNC2 can act as endogenous target mimics of miR156a and miR828a to reduce SPL9 and induce MYB114 expression, respectively, which lead to increased and decreased anthocyanin content as revealed by high-performance liquid chromatography analysis. Our results present the first global functional analysis of lncRNA in sea buckthorn and provide two essential regulators of anthocyanin biosynthesis, which provides new insights into the regulation of fruit quality.