Systemic dizocilpine (MK-801) facilitates performance in opposition to response bias

Previous research has established that dopamine signals are crucial in orienting behavior to reward. Less is known, however, about the psychopharmacology of task performance under small-reward conditions as compared to large-reward conditions. The current study examined the effects of the noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist dizocilpine (MK-801) on reaction time (RT) in a nose-poke task with rats completing an asymmetric reward schedule. In all trials, the rats were required to poke their nose in either the left or the right peripheral hole immediately adjacent to the centre hole when the corresponding light was illuminated. Depending on the stimulus-reward mapping, however, one position was associated with a large reward, while the alternative position was associated with a small reward. Correct performance was required in every trial; if the rat did not make a correct response within 20 s, the trial was aborted, and the same stimulus was presented again on the next trial. In this way, the rat was forced to perform the same visuo-spatial discrimination task under different reward conditions. Reaction times (ms) were faster for large-reward trials than for small-reward trials, replicating previous findings. At a dosage of MK-801 (0.04 mg/kg), there was no significant influence of on RT in large-reward trials. In contrast, the same dosage of MK-801 in small-reward trials produced a decrease in RT as compared to the control condition, implying an improvement of performance. Below 0.04 mg/kg of MK-801, a steady decrease of RT in small-trials was seen as a function of dosage. Above 0.04 mg/kg of MK-801, the majority of rats failed to perform the task at all, whereas the rats that did manage to perform the criterion of 80 correct trials in a session showed no difference in RT between large- and small-reward trials. These data indicate that the systemic administration of a relatively small dosage of MK-801 facilitates performance when reward is small. It is suggested that the facilitation may be due to the reinforcement of mechanisms that work in opposition to response bias. As a corollary, the study provides a useful paradigm to study the voluntary control of unavoidable action

Evaluative Processing of Food Images: Longer Viewing for Indecisive Preference Formation

The well-known gaze cascade hypothesis proposes that as people look longer at an item, they tend to show an increased preference for it. However, using single food images as stimuli, we recently obtained results that clearly deviated from the general proposal that the gaze both expresses and influences preference formation. Instead, the pattern of data depended on the self-determination of exposure duration as well as the type of evaluation task. In order to disambiguate how the type of evaluation determines the relationship between viewing and liking we conducted the present follow-up study, with a fixed response set size as opposed to the varying set sizes in our previous study. In non-exclusive evaluation tasks, subjects were asked how much they liked individual food images. The recorded response was a number from 1 to 3. In exclusive evaluation tasks, subjects were asked for each individual food image to give one of three response options toward a limited selection: include it, exclude it, or defer the judgment. When subjects were able to determine the exposure duration, both the non-exclusive and exclusive evaluations produced inverted U-shaped trends such that the polar ends of the evaluation (the positive and negative extremes) were associated with relatively short viewing times, whereas the middle category had the longest viewing times. Thus, the data once again provided firm evidence against the notion that longer viewing facilitates preference formation. Moreover, the fact that non-exclusive and exclusive evaluation produced similar inverted U-shaped patterns suggests that the response set size is the critical factor that accounts for the observations here versus in our previous study. When keeping the response set size constant, with an equal opportunity to observe inverted U-shaped patterns, the findings are suggestive of a role for the level of decisiveness in determining the length of viewing time. For items that can be categorically identified as positive or negative, the evaluations are soon completed, with relatively brief viewing times. The prolonged visual inspection for the middle category may reflect doubt or uncertainty during the evaluative processing, possibly with an increased effort of information integration before reaching a conclusion

Differentiation between Vergence and Saccadic Functional Activity within the Human Frontal Eye Fields and Midbrain Revealed through fMRI

Eye movement research has traditionally studied solely saccade and/or vergence eye movements by isolating these systems within a laboratory setting. While the neural correlates of saccadic eye movements are established, few studies have quantified the functional activity of vergence eye movements using fMRI. This study mapped the neural substrates of vergence eye movements and compared them to saccades to elucidate the spatial commonality and differentiation between these systems.The stimulus was presented in a block design where the 'off' stimulus was a sustained fixation and the 'on' stimulus was random vergence or saccadic eye movements. Data were collected with a 3T scanner. A general linear model (GLM) was used in conjunction with cluster size to determine significantly active regions. A paired t-test of the GLM beta weight coefficients was computed between the saccade and vergence functional activities to test the hypothesis that vergence and saccadic stimulation would have spatial differentiation in addition to shared neural substrates.Segregated functional activation was observed within the frontal eye fields where a portion of the functional activity from the vergence task was located anterior to the saccadic functional activity (z>2.3; p<0.03). An area within the midbrain was significantly correlated with the experimental design for the vergence but not the saccade data set. Similar functional activation was observed within the following regions of interest: the supplementary eye field, dorsolateral prefrontal cortex, ventral lateral prefrontal cortex, lateral intraparietal area, cuneus, precuneus, anterior and posterior cingulates, and cerebellar vermis. The functional activity from these regions was not different between the vergence and saccade data sets assessed by analyzing the beta weights of the paired t-test (p>0.2).Functional MRI can elucidate the differences between the vergence and saccade neural substrates within the frontal eye fields and midbrain

Neural Correlates of Effective Learning in Experienced Medical Decision-Makers

Accurate associative learning is often hindered by confirmation bias and success-chasing, which together can conspire to produce or solidify false beliefs in the decision-maker. We performed functional magnetic resonance imaging in 35 experienced physicians, while they learned to choose between two treatments in a series of virtual patient encounters. We estimated a learning model for each subject based on their observed behavior and this model divided clearly into high performers and low performers. The high performers showed small, but equal learning rates for both successes (positive outcomes) and failures (no response to the drug). In contrast, low performers showed very large and asymmetric learning rates, learning significantly more from successes than failures; a tendency that led to sub-optimal treatment choices. Consistently with these behavioral findings, high performers showed larger, more sustained BOLD responses to failed vs. successful outcomes in the dorsolateral prefrontal cortex and inferior parietal lobule while low performers displayed the opposite response profile. Furthermore, participants' learning asymmetry correlated with anticipatory activation in the nucleus accumbens at trial onset, well before outcome presentation. Subjects with anticipatory activation in the nucleus accumbens showed more success-chasing during learning. These results suggest that high performers' brains achieve better outcomes by attending to informative failures during training, rather than chasing the reward value of successes. The differential brain activations between high and low performers could potentially be developed into biomarkers to identify efficient learners on novel decision tasks, in medical or other contexts

c-Fos Expression during Temporal Order Judgment in Mice

The neuronal mechanisms for ordering sensory signals in time still need to be clarified despite a long history of research. To address this issue, we recently developed a behavioral task of temporal order judgment in mice. In the present study, we examined the expression of c-Fos, a marker of neural activation, in mice just after they carried out the temporal order judgment task. The expression of c-Fos was examined in C57BL/6N mice (male, n = 5) that were trained to judge the order of two air-puff stimuli delivered bilaterally to the right and left whiskers with stimulation intervals of 50–750 ms. The mice were rewarded with a food pellet when they responded by orienting their head toward the first stimulus (n = 2) or toward the second stimulus (n = 3) after a visual “go” signal. c-Fos-stained cell densities of these mice (test group) were compared with those of two control groups in coronal brain sections prepared at bregma −2, −1, 0, +1, and +2 mm by applying statistical parametric mapping to the c-Fos immuno-stained sections. The expression of c-Fos was significantly higher in the test group than in the other groups in the bilateral barrel fields of the primary somatosensory cortex, the left secondary somatosensory cortex, the dorsal part of the right secondary auditory cortex. Laminar analyses in the primary somatosensory cortex revealed that c-Fos expression in the test group was most evident in layers II and III, where callosal fibers project. The results suggest that temporal order judgment involves processing bilateral somatosensory signals through the supragranular layers of the primary sensory cortex and in the multimodal sensory areas, including marginal zone between the primary somatosensory cortex and the secondary sensory cortex

Predictive Coding or Evidence Accumulation? False Inference and Neuronal Fluctuations

Perceptual decisions can be made when sensory input affords an inference about what generated that input. Here, we report findings from two independent perceptual experiments conducted during functional magnetic resonance imaging (fMRI) with a sparse event-related design. The first experiment, in the visual modality, involved forced-choice discrimination of coherence in random dot kinematograms that contained either subliminal or periliminal motion coherence. The second experiment, in the auditory domain, involved free response detection of (non-semantic) near-threshold acoustic stimuli. We analysed fluctuations in ongoing neural activity, as indexed by fMRI, and found that neuronal activity in sensory areas (extrastriate visual and early auditory cortex) biases perceptual decisions towards correct inference and not towards a specific percept. Hits (detection of near-threshold stimuli) were preceded by significantly higher activity than both misses of identical stimuli or false alarms, in which percepts arise in the absence of appropriate sensory input. In accord with predictive coding models and the free-energy principle, this observation suggests that cortical activity in sensory brain areas reflects the precision of prediction errors and not just the sensory evidence or prediction errors per se

Mismatch Response to Polysyllabic Nonwords: A Neurophysiological Signature of Language Learning Capacity

Background: The ability to repeat polysyllabic nonwords such as ‘‘blonterstaping’’ has frequently been shown to correlate with language learning ability but it is not clear why such a correlation should exist. Three alternative explanations have been offered, stated in terms of differences in: (a) perceptual ability; (b) efficiency of phonological loop functioning; (c) preexisting vocabulary knowledge and/or articulatory skills. In the present study, we used event-related potentials to assess the contributions from these three factors to explaining individual variation in nonword repetition ability. Methodology/Principal Findings: 59 adults who were subdivided according to whether they were good or poor nonwordrepeaters participated. Electrophysiologically measured mismatch responses were recorded to changes in consonants as participants passively listened to a repeating four syllable CV-string. The consonant change could occur in one of four positions along the CV-string and we predicted that: (a) if nonword repetition depended purely on auditory discrimination ability, then reduced mismatch responses to all four consonant changes would be observed in the poor nonword-repeaters, (b) if it depended on encoding or decay of information in a capacity-limited phonological store, then a position specific decrease in mismatch response would be observed, (c) if neither cognitive capacity was involved, then the two groups of participants would provide equivalent mismatch responses. Consistent with our second hypothesis, a position specific difference located on the third syllable was observed in the late discriminative negativity (LDN) window (230–630 ms postsyllable onset). Conclusions/Significance: Our data thus confirm that people who are poorer at nonword repetition are less efficient in early processing of polysyllabic speech materials, but this impairment is not attributable to deficits in low level auditory discrimination. We conclude by discussing the significance of the observed relationship between LDN amplitude and nonword repetition ability and describe how this relatively little understood ERP component provides a biological window onto processes required for successful language learning

Dissociable Processes of Cognitive Control during Error and Non-Error Conflicts: A Study of the Stop Signal Task

Conflict detection and subsequent behavioral adjustment are critical to daily life, and how this process is controlled has been increasingly of interest. A medial cortical region which includes the anterior cingulate cortex (ACC) has been theorized to act as a conflict detector that can direct prefrontal activity for behavioral adjustments. This conflict monitoring hypothesis was supported by many imaging studies of the Stroop task, with a focus on non-error processes. Here we sought to examine whether this circuit could be generalized to the stop signal task (SST), another behavioral paradigm widely used to study cognitive control. In particular, with a procedure to elicit errors in the SST, we examined whether error and non-error control were mediated by the same pathways.In functional magnetic resonance imaging of 60 healthy adults, we demonstrated that the medial cortical activity during stop success (SS) as compared to go success (G) trials is correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials, though this correlation was not specific to the medial cortical region. Furthermore, thalamic and insular rather than medial cortical activation during stop error (SE) as compared to G trials correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials.Taken together, these new findings challenge a specific role of the ACC and support distinct pathways for error and non-error conflict processing in cognitive control

Social and Nonsocial Content Differentially Modulates Visual Attention and Autonomic Arousal in Rhesus Macaques

The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject-directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal). These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information relevant to interpreting the neural deficits underlying human psychiatric illnesses such as autism, schizophrenia and social anxiety disorder

Bilingualism Accentuates Children's Conversational Understanding

BACKGROUND: Although bilingualism is prevalent throughout the world, little is known about the extent to which it influences children's conversational understanding. Our investigation involved children aged 3-6 years exposed to one or more of four major languages: English, German, Italian, and Japanese. In two experiments, we examined the children's ability to identify responses to questions as violations of conversational maxims (to be informative and avoid redundancy, to speak the truth, be relevant, and be polite). PRINCIPAL FINDINGS: In Experiment 1, with increasing age, children showed greater sensitivity to maxim violations. Children in Italy who were bilingual in German and Italian (with German as the dominant language L1) significantly outperformed Italian monolinguals. In Experiment 2, children in England who were bilingual in English and Japanese (with English as L1) significantly outperformed Japanese monolinguals in Japan with vocabulary age partialled out. CONCLUSIONS: As the monolingual and bilingual groups had a similar family SES background (Experiment 1) and similar family cultural identity (Experiment 2), these results point to a specific role for early bilingualism in accentuating children's developing ability to appreciate effective communicative responses