Seeing an Auditory Object: Pupillary Light Response Reflects Covert Attention to Auditory Space and Object.

Attention to the relevant object and space is the brain's strategy to effectively process the information of interest in complex environments with limited neural resources. Numerous studies have documented how attention is allocated in the visual domain, whereas the nature of attention in the auditory domain has been much less explored. Here, we show that the pupillary light response can serve as a physiological index of auditory attentional shift and can be used to probe the relationship between space-based and object-based attention as well. Experiments demonstrated that the pupillary response corresponds to the luminance condition where the attended auditory object (e.g., spoken sentence) was located, regardless of whether attention was directed by a spatial (left or right) or nonspatial (e.g., the gender of the talker) cue and regardless of whether the sound was presented via headphones or loudspeakers. These effects on the pupillary light response could not be accounted for as a consequence of small (although observable) biases in gaze position drifting. The overall results imply a unified audiovisual representation of spatial attention. Auditory object-based attention contains the space representation of the attended auditory object, even when the object is oriented without explicit spatial guidance.

Temporal dynamics of auditory bistable perception correlated with fluctuation of baseline pupil size.

A dynamic neural network change, accompanied by cognitive shifts such as internal perceptual alternation in bistable stimuli, is reconciled by the discharge of noradrenergic locus coeruleus neurons. Transient pupil dilation as a consequence of the reconciliation with the neural network in bistable perception has been reported to precede the reported perceptual alternation. Here, we found that baseline pupil size, an index of temporal fluctuation of arousal level over a longer range of timescales than that for the transient pupil changes, relates to the frequency of perceptual alternation in auditory bistability. Baseline pupil size was defined as the mean pupil diameter over a period of 1 s prior to the task requirement (i.e., before the observation period for counting the perceptual alternations in Experiment 1 and reporting whether participants experienced the perceptual alternations in Experiment 2). The results showed that the baseline pupil size monotonically increased with an increasing number of perceptual alternations and its occurrence probability. Furthermore, a cross-correlation analysis indicates that baseline pupil size predicted perceptual alternation at least 35 s before the behavioral response and that the overall correspondence between pupil size and perceptual alternation was maintained over a sustained time window of 45 s at minimum. The overall results suggest that variability of baseline pupil size reflects the stochastic dynamics of arousal fluctuation in the brain related to bistable perception.

Attractiveness in the Eyes: A Possibility of Positive Loop between Transient Pupil Constriction and Facial Attraction.

Contrary to the long-held belief of a close linkage between pupil dilation and attractiveness, we found an early and transient pupil constriction response when participants viewed an attractive face (and the effect of luminance/contrast was controlled). While human participants were making an attractiveness judgment on faces, their pupil constricted more for the more attractive (as-to-be-rated) faces. Further experiments showed that the effect of pupil constriction to attractiveness judgment extended to intrinsically esthetic visual objects such as natural scene images (as well as faces) but not to line-drawing geometric figures. When participants were asked to judge the roundness of faces, pupil constriction still correlated with their attractiveness but not the roundness rating score, indicating the automaticity of the pupil constriction to attractiveness. When pupillary responses were manipulated implicitly by relative background luminance changes (from the prestimulus screen), the facial attractiveness ratings were in accordance with the amount of pupil constriction, which could not be explained solely by simultaneous or sequential luminance contrast. The overall results suggest that pupil constriction not only reflects but, as a part of self-monitoring and attribution mechanisms, also possibly contributes to facial attractiveness implicitly.

Dark, loud, and compact sounds induce frisson.

Frisson is characterised by tingling and tickling sensations with positive or negative feelings. However, it is still unknown what factors affect the intensity of frisson. We conducted experiments on the stimulus characteristics and individual's mood states and personality traits. Participants filled out self-reported questionnaires, including the Profile of Mood States, Beck Depression Inventory, and Big Five Inventory. They continuously indicated the subjective intensity of frisson throughout a 17-min experiment while listening to binaural brushing and tapping sounds through headphones. In the interviews after the experiments, participants reported that tingling and tickling sensations mainly originated on their ears, neck, shoulders, and back. Cross-correlation results showed that the intensity of frisson was closely linked to the acoustic features of auditory stimuli, including their amplitude, spectral centroid, and spectral bandwidth. This suggests that proximal sounds with dark and compact timbre trigger frisson. The peak of correlation between frisson and the acoustic feature was observed 2 s after the acoustic feature changed, suggesting that bottom-up auditory inputs modulate skin-related modalities. We also found that participants with anxiety were sensitive to frisson. Our results provide important clues to understanding the mechanisms of auditory-somatosensory interactions.

Microsaccadic Eye Movements but not Pupillary Dilation Response Characterizes the Crossmodal Freezing Effect.

In typical spatial orienting tasks, the perception of crossmodal (e.g., audiovisual) stimuli evokes greater pupil dilation and microsaccade inhibition than unisensory stimuli (e.g., visual). The characteristic pupil dilation and microsaccade inhibition has been observed in response to "salient" events/stimuli. Although the "saliency" account is appealing in the spatial domain, whether this occurs in the temporal context remains largely unknown. Here, in a brief temporal scale (within 1 s) and with the working mechanism of involuntary temporal attention, we investigated how eye metric characteristics reflect the temporal dynamics of perceptual organization, with and without multisensory integration. We adopted the crossmodal freezing paradigm using the classical Ternus apparent motion. Results showed that synchronous beeps biased the perceptual report for group motion and triggered the prolonged sound-induced oculomotor inhibition (OMI), whereas the sound-induced OMI was not obvious in a crossmodal task-free scenario (visual localization without audiovisual integration). A general pupil dilation response was observed in the presence of sounds in both visual Ternus motion categorization and visual localization tasks. This study provides the first empirical account of crossmodal integration by capturing microsaccades within a brief temporal scale; OMI but not pupillary dilation response characterizes task-specific audiovisual integration (shown by the crossmodal freezing effect).

Pupil-linked phasic arousal evoked by violation but not emergence of regularity within rapid sound sequences.

The ability to track the statistics of our surroundings is a key computational challenge. A prominent theory proposes that the brain monitors for unexpected uncertainty - events which deviate substantially from model predictions, indicating model failure. Norepinephrine is thought to play a key role in this process by serving as an interrupt signal, initiating model-resetting. However, evidence is from paradigms where participants actively monitored stimulus statistics. To determine whether Norepinephrine routinely reports the statistical structure of our surroundings, even when not behaviourally relevant, we used rapid tone-pip sequences that contained salient pattern-changes associated with abrupt structural violations vs. emergence of regular structure. Phasic pupil dilations (PDR) were monitored to assess Norepinephrine. We reveal a remarkable specificity: When not behaviourally relevant, only abrupt structural violations evoke a PDR. The results demonstrate that Norepinephrine tracks unexpected uncertainty on rapid time scales relevant to sensory signals.

Pupillary dilation response reflects surprising moments in music.

There are indications that the pupillary dilation response (PDR) reflects surprising moments in an auditory sequence such as the appearance of a deviant noise against repetitively presented pure tones (4), and salient and loud sounds that are evaluated by human paricipants subjectively (12). In the current study, we further examined whether the reflection of PDR in auditory surprise can be accumulated and revealed in complex and yet structured auditory stimuli, i.e., music, and when the surprise is defined subjectively. Participants listened to 15 excerpts of music while their pupillary responses were recorded. In the surprise-rating session, participants rated how surprising an instance in the excerpt was, i.e., rich in variation versus monotonous, while they listened to it. In the passive-listening session, they listened to the same 15 excerpts again but were not involved in any task. The pupil diameter data obtained from both sessions were time-aligned to the rating data obtained from the surprise-rating session. Results showed that in both sessions, mean pupil diameter was larger at moments rated more surprising than unsurprising. The result suggests that the PDR reflects surprise in music automatically.

WITHDRAWN: Auditory Surprise Model Based on Pattern Retrieval from the Past Observation.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the authors. The authors regrets that the reason for withdrawal is due to an disagreement in authorship and in scope of data disclosure. The authors apologize to the readers for this unfortunate error.

Human Pupillary Dilation Response to Deviant Auditory Stimuli: Effects of Stimulus Properties and Voluntary Attention.

A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR) that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants' pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention.

Correspondences among pupillary dilation response, subjective salience of sounds, and loudness.

A pupillary dilation response is known to be evoked by salient deviant or contrast auditory stimuli, but so far a direct link between it and subjective salience has been lacking. In two experiments, participants listened to various environmental sounds while their pupillary responses were recorded. In separate sessions, participants performed subjective pairwise-comparison tasks on the sounds with respect to their salience, loudness, vigorousness, preference, beauty, annoyance, and hardness. The pairwise-comparison data were converted to ratings on the Thurstone scale. The results showed a close link between subjective judgments of salience and loudness. The pupil dilated in response to the sound presentations, regardless of sound type. Most importantly, this pupillary dilation response to an auditory stimulus positively correlated with the subjective salience, as well as the loudness, of the sounds (Exp. 1). When the loudnesses of the sounds were identical, the pupil responses to each sound were similar and were not correlated with the subjective judgments of salience or loudness (Exp. 2). This finding was further confirmed by analyses based on individual stimulus pairs and participants. In Experiment 3, when salience and loudness were manipulated by systematically changing the sound pressure level and acoustic characteristics, the pupillary dilation response reflected the changes in both manipulated factors. A regression analysis showed a nearly perfect linear correlation between the pupillary dilation response and loudness. The overall results suggest that the pupillary dilation response reflects the subjective salience of sounds, which is defined, or is heavily influenced, by loudness.

Capturing attention is not that simple: different mechanisms for stimulus-driven and contingent capture.

Attentional orienting can be involuntarily directed to task-irrelevant stimuli, but it remains unsolved whether such attentional capture is contingent on top-down settings or could be purely stimulus-driven. We propose that attentional capture depends on the stimulus property because transient and static features are processed differently; thus, they might be modulated differently by top-down controls. To test this hybrid account, we adopted a spatial cuing paradigm in which a noninformative onset or color cue preceded an onset or color target with various stimulus onset asynchronies (SOAs). Results showed that the onset cue captured attention regardless of target type at short-but not long-SOAs. In contrast, the color cue captured attention at short and long SOAs, but only with a color target. The overall pattern of results corroborates our hypothesis, suggesting that different mechanisms are at work for stimulus-driven capture (by onset) and contingent capture (by color). Stimulus-driven capture elicits reflexive involuntary orienting, and contingent capture elicits voluntary feature-based enhancement.

Cortical stimulation consolidates and reactivates visual experience: neural plasticity from magnetic entrainment of visual activity.

Delivering transcranial magnetic stimulation (TMS) shortly after the end of a visual stimulus can cause a TMS-induced 'replay' or 'visual echo' of the visual percept. In the current study, we find an entrainment effect that after repeated elicitations of TMS-induced replay with the same visual stimulus, the replay can be induced by TMS alone, without the need for the physical visual stimulus. In Experiment 1, we used a subjective rating task to examine the phenomenal aspects of TMS-entrained replays. In Experiment 2, we used an objective masking paradigm to quantitatively validate the phenomenon and to examine the involvement of low-level mechanisms. Results showed that the TMS-entrained replay was not only phenomenally experienced (Exp.1), but also able to hamper letter identification (Exp.2). The findings have implications in several directions: (1) the visual cortical representation and iconic memory, (2) experience-based plasticity in the visual cortex, and (3) their relationship to visual awareness.

Happy faces are preferred regardless of familiarity--sad faces are preferred only when familiar.

Familiarity leads to preference (e.g., the mere exposure effect), yet it remains unknown whether it is objective familiarity, that is, repetitive exposure, or subjective familiarity that contributes to preference. In addition, it is unexplored whether and how different emotions influence familiarity-related preference. The authors investigated whether happy or sad faces are preferred or perceived as more familiar and whether this subjective familiarity judgment correlates with preference for different emotional faces. An emotional face--happy or sad--was paired with a neutral face, and participants rated the relative preference and familiarity of each of the paired faces. For preference judgment, happy faces were preferred and sad faces were less preferred, compared with neutral faces. For familiarity judgment, happy faces did not show any bias, but sad faces were perceived as less familiar than neutral faces. Item-by-item correlational analyses show preference for sad faces--but not happy faces--positively correlate with familiarity. These results suggest a direct link between positive emotion and preference, and argue at least partly against a common cause for familiarity and preference. Instead, facial expression of different emotional valence modulates the link between familiarity and preference.

Loading dose required to achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multidrug-resistant gram-positive infections.

Teicoplanin is an antibiotic drug prescribed for the treatment of multidrug-resistant Gram-positive infections. However, there is currently no consensus as to the optimal teicoplanin loading dose. The objective of this study was to compare plasma concentrations of teicoplanin in patients with multidrug-resistant Gram-positive infections after the administration of two different loading doses. Two groups of patients were infused intravenously with four loading doses of 6 mg/kg body-weight (group A, n = 12) or 12 mg/kg body-weight (group B, n = 11). The first three loading doses were administered at 12-hr intervals, and the fourth was given 24 hr after the third dose. Maintenance doses of 6 mg/kg were administered every day, every other day or every third day depending on the individual's creatinine clearance, and teicoplanin trough plasma concentrations were monitored. Only samples obtained on the same day for both groups were compared statistically. A higher percentage of group B patients achieved the desired therapeutic concentration of teicoplanin (C(min.)  ≥ 10 mg/L) on days 2 and 3 (90.0% and 100%, respectively) compared with patients in group A (18.2% and 16.7%, respectively) (p < 0.001). In addition, more patients in group B achieved therapeutic concentrations from days 2 through 12. In conclusion, despite limitations in drawing definitive conclusions because of a relatively small sample size and variability in renal impairment among patients, our findings suggest that a teicoplanin loading dose of 12 mg/kg body-weight results in a safe and rapid attainment of therapeutic trough plasma concentrations. This regimen may enhance treatment efficacy.

Novelty vs. Familiarity Principles in Preference Decisions: Task-Context of Past Experience Matters.

Our preferences are shaped by past experience in many ways, but a systematic understanding of the factors is yet to be achieved. For example, studies of the mere exposure effect show that experience with an item leads to increased liking (familiarity preference), but the exact opposite tendency is found in other studies utilizing dishabituation (novelty preference). Recently, it has been found that image category affects whether familiarity or novelty preference emerges from repeated stimulus exposure (Park et al., 2010). Faces elicited familiarity preference, but natural scenes elicited novelty preference. In their task, preference judgments were made throughout all exposures, raising the question of whether the task-context during exposure was involved. We adapt their paradigm, testing if passive exposure or objective judgment task-contexts lead to different results. Results showed that after passive viewing, familiar faces were preferred, but no preference bias in either direction was found with natural scenes, or with geometric figures (control). After exposure during the objective judgment task, familiar faces were preferred, novel natural scenes were preferred, and no preference bias was found with geometric figures. The overall results replicate the segregation of preference biases across object categories and suggest that the preference for familiar faces and novel natural scenes are modulated by task-context memory at different processing levels or selection involvement. Possible underlying mechanisms of the two types of preferences are discussed.

Interaction between stimulus-driven orienting and top-down modulation in attentional capture.

The issue whether attentional capture is determined by top-down factors or can be stimulus-driven remains unsolved. To examine this, we used a spatial cueing paradigm with set size four and eight in which a color target is preceded by an uninformative cue (color or onset) that either matches or does not match the target-defining feature. The critical manipulation lies in adding no-cue trials to make the subsequent first with-cue trial unexpected, which reveals the stimulus-driven component. For the onset cue, the first-trial analysis indicated attentional capture at set size four and eight, whereas results from the average data indicated attentional capture at set size eight but not at set size four. For the color cue, attentional capture was found in the average data but not in the first trial, regardless of set size. These results can be explained by the interactive processing of early stimulus-driven activation followed by top-down modulation.

On the generality of the displaywide contingent orienting hypothesis: can a visual onset capture attention without top-down control settings for displaywide onset?

The contingent orienting hypothesis (Folk, Remington, & Johnston, 1992) states that attentional capture is contingent on top-down control settings induced by task demands. Past studies supporting this hypothesis have identified three kinds of top-down control settings: for target-specific features, for the strategy to search for a singleton, and for visual features in the target display as a whole. Previously, we have found stimulus-driven capture by onset that was not contingent on the first two kinds of settings (Yeh & Liao, 2008). The current study aims to test the third kind: the displaywide contingent orienting hypothesis (Gibson & Kelsey, 1998). Specifically, we ask whether an onset stimulus can still capture attention in the spatial cueing paradigm when attentional control settings for the displaywide onset of the target are excluded by making all letters in the target display emerge from placeholders. Results show that a preceding uninformative onset cue still captured attention to its location in a stimulus-driven fashion, whereas a color cue captured attention only when it was contingent on the setting for displaywide color. These results raise doubts as to the generality of the displaywide contingent orienting hypothesis and help delineate the boundary conditions on this hypothesis.

On the generality of the contingent orienting hypothesis.

The contingent-orienting hypothesis states that attentional capture by a task-irrelevant stimulus is contingent on whether that stimulus shares a feature property that is critical to the task at hand [Folk, C. L., Remington, R. W., & Johnston, J. C. (1992). Involuntary covert orienting is contingent on attentional control settings. Journal of Experimental Psychology: Human Perception and Performance, 18, 1030-1044]. Studies supporting this hypothesis have mostly used set size four displays throughout the experiment and thus constrict its ecological validity, since conclusions drawn from experiments using fixed set-size displays may not be generalized to other conditions with different set sizes. We used a spatial cueing paradigm in which a non-informative onset or color cue preceded an onset or a color target, and manipulated set size as a within- or between-subject factor. In four experiments, the original finding of Folk et al. (1992) was replicated only when a fixed set size (four) was used throughout. When both set-size four and eight were used in an experiment, stimulus-driven capture by onset in search of a color target was found even for set-size four displays. These results raise doubts as to the generality of the contingent-orienting hypothesis and help to delineate the boundary conditions on this hypothesis.