Synthesis of thieno[2,3-h]-/[3,2-h]quinolines and thieno[2,3-f] quinolines by Brønsted acid mediated cycloisomerisation.

Several thieno[2,3-h]-/[3,2-h]- and [2,3-f]quinolines have been synthesised from 2,3-dihalogenated pyridines or -quinolines by site-selective Pd catalysed cross-coupling reactions and Brønsted acid mediated cycloisomerisations as the final key step. This newly developed synthetic strategy is used in a modular way to synthesize diverse regioisomeric derivatives, tolerates various functional groups, and proceeds with high selectivity, and the desired final products have been isolated in high overall yields.

Orienting attention to visual or verbal/auditory imagery differentially impairs the processing of visual stimuli.

When attention is oriented toward inner thoughts, as spontaneously occurs during mind wandering, the processing of external information is attenuated. However, the potential effects of thought's content regarding sensory attenuation are still unknown. The present study aims to assess if the representational format of thoughts, such as visual imagery or inner speech, might differentially affect the sensory processing of external stimuli. We recorded the brain activity of 20 participants (12 women) while they were exposed to a probe visual stimulus in three different conditions: executing a task on the visual probe (externally oriented attention), and two conditions involving inward-turned attention i.e. generating inner speech and performing visual imagery. Event-related potentials results showed that the P1 amplitude, related with sensory response, was significantly attenuated during both task involving inward attention compared with external task. When both representational formats were compared, the visual imagery condition showed stronger attenuation in sensory processing than inner speech condition. Alpha power in visual areas was measured as an index of cortical inhibition. Larger alpha amplitude was found when participants engaged in an internal thought contrasted with the external task, with visual imagery showing even more alpha power than inner speech condition. Our results show, for the first time to our knowledge, that visual attentional processing to external stimuli during self-generated thoughts is differentially affected by the representational format of the ongoing train of thoughts.

Auditory Feedback Differentially Modulates Behavioral and Neural Markers of Objective and Subjective Performance When Tapping to Your Heartbeat.

Interoception, the perception of our body internal signals, plays a key role in maintaining homeostasis and guiding our behavior. Sometimes, we become aware of our body signals and use them in planning and strategic thinking. Here, we show behavioral and neural dissociations between learning to follow one's own heartbeat and metacognitive awareness of one's performance, in a heartbeat-tapping task performed before and after auditory feedback. The electroencephalography amplitude of the heartbeat-evoked potential in interoceptive learners, that is, participants whose accuracy of tapping to their heartbeat improved after auditory feedback, was higher compared with non-learners. However, an increase in gamma phase synchrony (30-45 Hz) after the heartbeat auditory feedback was present only in those participants showing agreement between objective interoceptive performance and metacognitive awareness. Source localization in a group of participants and direct cortical recordings in a single patient identified a network hub for interoceptive learning in the insular cortex. In summary, interoceptive learning may be mediated by the right insular response to the heartbeat, whereas metacognitive awareness of learning may be mediated by widespread cortical synchronization patterns.

Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence.

It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25-45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception.

Ten years of Nature Reviews Neuroscience: insights from the highly cited.

To celebrate the first 10 years of Nature Reviews Neuroscience, we invited the authors of the most cited article of each year to look back on the state of their field of research at the time of publication and the impact their article has had, and to discuss the questions that might be answered in the next 10 years. This selection of highly cited articles provides interesting snapshots of the progress that has been made in diverse areas of neuroscience. They show the enormous influence of neuroimaging techniques and highlight concepts that have generated substantial interest in the past decade, such as neuroimmunology, social neuroscience and the 'network approach' to brain function. These advancements will pave the way for further exciting discoveries that lie ahead.

The dual facet of gamma oscillations: separate visual and decision making circuits as revealed by simultaneous EEG/fMRI.

It remains an outstanding question whether gamma-band oscillations reflect unitary cognitive processes within the same task. EEG/MEG studies do lack the resolution or coverage to address the highly debated question whether single gamma activity patterns are linked with multiple cognitive modules or alternatively each pattern associates with a specific cognitive module, within the same coherent perceptual task. One way to disentangle these issues would be to provide direct identification of their sources, by combining different techniques. Here, we directly examined these questions by performing simultaneous EEG/fMRI using an ambiguous perception paradigm requiring holistic integration. We found that distinct gamma frequency sub-bands reflect different neural substrates and cognitive mechanisms when comparing object perception states vs. no categorical perception. A low gamma sub-band (near 40 Hz) activity was tightly related to the decision making network, and in particular the anterior insula. A high gamma sub-band (∼60 Hz) could be linked to early visual processing regions. The demonstration of a clear functional topography for distinct gamma sub-bands within the same task shows that distinct gamma-band modulations underlie sensory processing and perceptual decision mechanisms.

Executive Functions and Theory of Mind in Teachers and Non-Teachers.

Human teaching is a key behavior for the socialization of cultural knowledge. Previous studies suggest that human teaching behavior would support the development of executive and ToM skills, which in turn would refine the teaching behavior. Given this connection, it raises the question of whether subjects with professional training in teaching also have more efficient executive and ToM systems. To shed light on this issue, in the present study we compared the performance of professional teachers (N = 20, age range = 35-61 years) with a matched control group of non-teachers (N = 20, age range: 29-64 years) on tasks measuring working memory (Sternberg Task), cognitive flexibility (Wisconsin Card Sorting Test), executive control (Attention Network Test), along with online ToM skills (Frith-Happé Animations Task), emotion recognition (Reading the Mind in the Eyes Test) and first-order and second-order ToM (Yoni Task). We found that teachers were significantly more accurate on tasks involving cognitive flexibility (p = .014) and working memory (p = .040), and more efficient on tasks requiring executive control of attention (p = .046), compared to non-teachers. In ToM tasks, differences in accuracy between teachers and non-teachers were not found. But, teachers were slower to respond than non-teachers (about 2 s difference) on tasks involving emotion recognition (p = .0007) and the use of second-order affective ToM (p = .006). Collectively, our findings raise an interesting link between professional teaching and the development of cognitive skills critical for decision-making in challenging social contexts such as the classroom. Future research could explore ways to foster teachers' strengths in cognitive flexibility, working memory, and executive control of attention to enhance teaching strategies and student learning outcomes. Additionally, exploring factors behind slower response times in affective ToM tasks can guide teacher-training programs focused on interpersonal skills and improve teacher-student interactions.

Assessing Spatial User Experience for Design Guidelines: A Comparative Study of Outpatient Waiting Rooms With Conventional Versus Modern Features.

OBJECTIVES: Identify waiting room design features that are most appreciated by outpatients and their companions in conventional and modern waiting rooms. Evaluate if end users evaluate the environment differently from experts and in what aspects. Provide evidence-based design guidelines that orient designers and healthcare managers. BACKGROUND: Built environments are relevant in patients' evaluation of overall healthcare service. For outpatients, waiting frequently consumes the largest amount of time; thus, waiting room interior design has great potential to enhance their experience. METHODS: This study compares perceptions of two types of waiting rooms-conventional and modern-based on the spatial user experience (SUE) model. In the first stage of the study, we compared user evaluations of conventional waiting rooms (n = 137) and modern waiting rooms (n = 426) with respect to the eight SUE model dimensions using multigroup structural equation modeling. In the second stage, an expert ergonomist and two professional interior designers assessed both types of waiting rooms. RESULTS: Results showed that modern waiting rooms were perceived to be significantly better in all SUE dimensions. We also found experts' evaluations were overall consistent with users' perceptions. Discrepancies were only found in temperature perception, signage evaluation, and spatial appreciation. CONCLUSIONS: Participants valued modern style waiting room features such as good quality signage, use of armchairs and sofas, a controlled environment, and decoration. We suggest involving end users in the design process to respond to their needs and promote a positive experience. Finally, we provide easy-to-adopt design guidelines to improve patients' waiting room experience.

Expectations change the signatures and timing of electrophysiological correlates of perceptual awareness.

Previous experience allows the brain to predict what comes next. How these expectations affect conscious experience is poorly understood. In particular, it is unknown whether and when expectations interact with sensory evidence in granting access to conscious perception, and how this is reflected electrophysiologically. Here, we parametrically manipulate sensory evidence and expectations while measuring event-related potentials in human subjects to assess the time course of evoked responses that correlate with subjective visibility, the properties of the stimuli, and/or perceptual expectations. We found that expectations lower the threshold of conscious perception and reduce the latency of neuronal signatures differentiating seen and unseen stimuli. Without expectations, this differentiation occurs ∼300 ms and with expectations ∼200 ms after stimulus in occipitoparietal sensors. The amplitude of this differentiating response component (P2) decreases as visibility increases, regardless of whether this increase is attributable to enhanced sensory evidence and/or the gradual buildup of perceptual expectations. Importantly, at matched performance levels, responses to seen and unseen stimuli differed regardless of the physical stimulus properties. These findings indicate that the latency of the neuronal correlates of access to consciousness depend on whether access is driven by stimulus saliency or by a combination of expectations and sensory evidence.

The development of neural synchrony reflects late maturation and restructuring of functional networks in humans.

Brain development is characterized by maturational processes that span the period from childhood through adolescence to adulthood, but little is known whether and how developmental processes differ during these phases. We analyzed the development of functional networks by measuring neural synchrony in EEG recordings during a Gestalt perception task in 68 participants ranging in age from 6 to 21 years. Until early adolescence, developmental improvements in cognitive performance were accompanied by increases in neural synchrony. This developmental phase was followed by an unexpected decrease in neural synchrony that occurred during late adolescence and was associated with reduced performance. After this period of destabilization, we observed a reorganization of synchronization patterns that was accompanied by pronounced increases in gamma-band power and in theta and beta phase synchrony. These findings provide evidence for the relationship between neural synchrony and late brain development that has important implications for the understanding of adolescence as a critical period of brain maturation.

Bi-Stable Perception: Self-Coordinating Brain Regions to Make-Up the Mind.

Bi-stable perception is a strong instance of cognitive self-organization, providing a research model for how 'the brain makes up its mind.' The complexity of perceptual bistability prevents a simple attribution of functions to areas, because many cognitive processes, recruiting multiple brain regions, are simultaneously involved. The functional magnetic resonance imaging (fMRI) evidence suggests the activation of a large network of distant brain areas. Concurrently, electroencephalographic and magnetoencephalographic (MEEG) literature shows sub second oscillatory activity and phase synchrony on several frequency bands. Strongly represented are beta and gamma bands, often associated with neural/cognitive integration processes. The spatial extension and short duration of brain activities suggests the need for a fast, large-scale neural coordination mechanism. To address the range of temporo-spatial scales involved, we systematize the current knowledge from mathematical models, cognitive sciences and neuroscience at large, from single-cell- to system-level research, including evidence from human and non-human primates. Surprisingly, despite evidence spanning through different organization levels, models, and experimental approaches, the scarcity of integrative studies is evident. In a final section of the review we dwell on the reasons behind such scarcity and on the need of integration in order to achieve a real understanding of the complexities underlying bi-stable perception processes.

Increase in Beta Power Reflects Attentional Top-Down Modulation After Psychosocial Stress Induction.

Selective attention depends on goal-directed and stimulus-driven modulatory factors, each relayed by different brain rhythms. Under certain circumstances, stress-related states can change the balance between goal-directed and stimulus-driven factors. However, the neuronal mechanisms underlying these changes remain unclear. In this study, we explored how psychosocial stress can modulate brain rhythms during an attentional task and a task-free period. We recorded the EEG and ECG activity of 42 healthy participants subjected to either the Trier Social Stress Test (TSST), a controlled procedure to induce stress, or a comparable control protocol (same physical and cognitive effort but without the stress component), flanked by an attentional task, a 90 s of task-free period and a state of anxiety questionnaire. We observed that psychosocial stress induced an increase in heart rate (HR), self-reported anxiety, and alpha power synchronization. Also, psychosocial stress evoked a relative beta power increase during correct trials of the attentional task, which correlates positively with anxiety and heart rate increase, and inversely with attentional accuracy. These results suggest that psychosocial stress affects performance by redirecting attentional resources toward internal threat-related thoughts. An increment of endogenous top-down modulation reflected an increased beta-band activity that may serve as a compensatory mechanism to redirect attentional resources toward the ongoing task. The data obtained here may contribute to designing new ways of clinical management of the human stress response in the future and could help to minimize the damaging effects of persistent stressful experiences.

Cortical oscillatory activity is critical for working memory as revealed by deficits in early-onset schizophrenia.

Impairments in working memory (WM) are a core cognitive deficit in schizophrenia. Neurophysiological models suggest that deficits during WM maintenance in schizophrenia may be explained by abnormalities in the GABAergic system, which will lead to deficits in high-frequency oscillations. However, it is not yet clear which of the three WM phases (encoding, maintenance, retrieval) are affected by dysfunctional oscillatory activity. We investigated the relationship between impairments in oscillatory activity in a broad frequency range (3-100 Hz) and WM load in the different phases of WM in 14 patients with early-onset schizophrenia and 14 matched control participants using a delayed matching to sample paradigm. During encoding, successful memorization was predicted by evoked theta, alpha, and beta oscillatory activity in controls. Patients showed severe reductions in the evoked activity in these frequency bands. During early WM maintenance, patients showed a comparable WM load-dependent increase in induced alpha and gamma activity to controls. In contrast, during the later maintenance phase, patients showed a shift in the peak of induced gamma activity to the lower WM load conditions. Finally, induced theta and gamma activity were reduced in patients during retrieval. Our findings suggest that the WM deficit in schizophrenia is associated with impaired oscillatory activity during all phases of the task and that the cortical storage system reaches its capacity limit at lower loads. Inability to maintain oscillatory activity in specific frequency bands could thus result in the information overload that may underlie both cognitive deficits and psychopathological symptoms of schizophrenia.

(Micro)Saccades, corollary activity and cortical oscillations.

In natural vision, attention and eye movements are linked. Furthermore, eye movements structure the inflow of information into the visual system. Saccades, where little vision occurs, alternate with fixations, when most vision occurs. A mechanism must be in place to maximize information intake during fixations. Oscillatory synchrony has been proposed as a mechanism for rapid and reliable communication of signals, subserving cognitive functions such as attention and object identification. We propose that saccade-related corollary activity has a crucial role in anticipatory preparation of visual centers, which interacts with ongoing oscillation, favoring the processing of postfixational signals. During prolonged fixations, microsaccades could be generated to exploit this mechanism. Studying this interplay between the sensory and the motor system will provide novel insight into the dynamics of natural vision.

Brain-to-Brain Coupling in the Gamma-Band as a Marker of Shared Intentionality.

Cooperation and competition are two ways of social interaction keys to life in society. Recent EEG-based hyperscanning studies reveal that cooperative and competitive interactions induce an increase in interbrain coupling. However, whether this interbrain coupling effect is just a reflection of inter-subject motor coordination or can also signal the type of social interaction is unknown. Here, we show that behavioral coordination and social interaction type can be distinguished according to the frequency of oscillation in which the brains are coupled. We use EEG to simultaneously measure the brain activity of pairs of subjects, while they were performing a visual cue-target task in a cooperative and competitive manner. Behavioral responses were quasi-simultaneous between subject pairs for both competitive and cooperative conditions, with faster average response times for the competitive condition. Concerning brain activity, we found increased interbrain coupling in theta band (3-7 Hz) during cooperation and competition, with stronger coupling during competitive interactions. This increase of interbrain theta coupling correlated with a decrease in reaction times of the dyads. Interestingly, we also found an increase in brain-to-brain coupling in gamma band (38-42 Hz) only during cooperative interactions. Unlike the theta coupling effect, the gamma interbrain coupling did not correlate with dyads' reaction times. Taken together, these results suggest that theta interbrain coupling could be linked to motor coordination processes common to cooperative and competitive interactions, while gamma brain-to-brain coupling emerges as an electrophysiological marker of shared intentionality during cooperative interactions.

Surgical Stabilization of Rib Fractures: Indications, Techniques, and Pitfalls.

Rib fractures are a common thoracic injury that is encountered in 20% to 39% of patients with blunt chest trauma and is associated with substantial morbidity and mortality1,2. Traditionally, the majority of patient with rib fractures have been managed nonoperatively. Recently, the utilization of surgical stabilization of rib fractures has increased considerably because the procedure has shown improved outcomes3-5. DESCRIPTION: Surgical stabilization should be considered in cases of multiple bicortically displaced rib fractures, especially in those with a flail chest and/or a concomitant ipsilateral displaced midshaft clavicular fracture or sternal fracture, as such cases may result in thoracic wall instability. For surgical stabilization of rib fractures, we classify rib fractures by location, type of fracture, and degree of displacement after obtaining thin-sliced chest computed tomography (CT) scans. The incision is selected depending on the fracture location, and the surgical technique is chosen relevant to the type of fracture. Single-lung intubation is preferred if there is no severe contralateral pulmonary contusion. We favor performing video-assisted thoracoscopy if possible to control bleeding, evacuate hematomas, repair a lung, and perform cryoablation of the intercostal nerves. A lateral approach is considered to be the main surgical approach because it allows access to the majority of rib fractures. A curvilinear skin incision is made overlying the fractured ribs. Posterior rib fractures are exposed through a vertical incision within the triangle of auscultation, and anterior fractures, through a transverse inframammary incision. The muscle-sparing technique, splitting alongside fibers without transection, should be utilized if possible and supplemented by muscle retraction. For surgical stabilization of rib fractures, we currently prefer precontoured side and rib-specific plates with threaded holes and self-tapping locking screws. Polymer cable cerclage is used to enhance plating of longitudinal fractures, rib fractures near the spine, osteoporotic ribs, and injuries of rib cartilage. The third to eighth ribs are plated most often. Intercostal muscle deficit, if present, is repaired with a xenograft patch. In comminuted rib fractures, the bone gap is bridged with bone graft. Surgical stabilization of rib fractures is recommended within the first 7 days after trauma, preferably within the first 3 days6-8. ALTERNATIVES: Nonoperative treatment alternatives include (1) epidural analgesia when not contraindicated because of anticoagulant venous thromboembolism prophylaxis9,10; (2) thoracic paravertebral blockage, e.g., serratus anterior or erector spinae plane nerve block11,12; (3) intercostal nerve block; (4) intravenous or enteral analgesics, e.g., opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs); (5) intrapleural analgesia, e.g., bupivacaine infusion; and (6) multimodal analgesia that incorporates regional techniques, systemic analgesics, and analgesic adjuncts9. RATIONALE: Surgical stabilization of rib fractures is a safe and effective method to treat displaced rib fractures. The procedure provides definitive stabilization of fractures, improves pulmonary function, lessens pain medication requirements, prevents deformity formation, and results in reduced morbidity and mortality.

Humor Improves Women's but Impairs Men's Iowa Gambling Task Performance.

The Iowa Gambling Task (IGT) is a popular method for examining real-life decision-making. Research has shown gender related differences in performance, in that men consistently outperform women. It has been suggested that these performance differences are related to decreased emotional control in women compared to men. Given the likely role of emotion in these gender differences, in the present study, we examine the effect of a humor induction on IGT performance and whether the effect of humor is moderated by gender. IGT performance and parameters from the Expectancy Valence Model (EVM) were measured in 68 university students (34 men; mean age 22.02, SD = 4.3 and 34 women; mean age 22.3, SD = 4.1) during a 100 trial-IGT task. Participants were exposed to a brief video before each of the IGT decisions available; one half of the samples (17 men and 17 women) was exposed to 100 humor videos, while the other half was exposed to 100 non-humor videos during the task. We observed a significant interaction between gender and humor, such that under humor, women's performance during the last block (trials 80-100) improved (compared to women under non-humor), whereas men's performance during the last block was worse (compared to men under non-humor). Consistent with previous work, under non-humor, men outperformed women in the last block. Lastly, our EVM results show that humor impacts the learning mechanisms of decision-making differently in men and women. Humor impaired men's ability to acquire knowledge about the payoff structure of the decks, and as a consequence, they were stuck in suboptimal performance. On the other hand, humor facilitated women's ability to explore and to learn from experience, improving performance. These findings deepen our understanding of the mechanisms underlying IGT decision-making and differential effects of humor in men and women.

Synchronization of neural activity across cortical areas correlates with conscious perception.

Subliminal stimuli can be deeply processed and activate similar brain areas as consciously perceived stimuli. This raises the question which signatures of neural activity critically differentiate conscious from unconscious processing. Transient synchronization of neural activity has been proposed as a neural correlate of conscious perception. Here we test this proposal by comparing the electrophysiological responses related to the processing of visible and invisible words in a delayed matching to sample task. Both perceived and nonperceived words caused a similar increase of local (gamma) oscillations in the EEG, but only perceived words induced a transient long-distance synchronization of gamma oscillations across widely separated regions of the brain. After this transient period of temporal coordination, the electrographic signatures of conscious and unconscious processes continue to diverge. Only words reported as perceived induced (1) enhanced theta oscillations over frontal regions during the maintenance interval, (2) an increase of the P300 component of the event-related potential, and (3) an increase in power and phase synchrony of gamma oscillations before the anticipated presentation of the test word. We propose that the critical process mediating the access to conscious perception is the early transient global increase of phase synchrony of oscillatory activity in the gamma frequency range.

Plasticity in primary somatosensory cortex resulting from environmentally enriched stimulation and sensory discrimination training.

We studied primary-somatosensory cortical plasticity due to selective stimulation of the sensory periphery by two procedures of active exploration in adult rats. Subjects, left with only three adjacent whiskers, were trained in a roughness discrimination task or maintained in a tactile enriched environment. Either training or enrichment produced 3-fold increases in the barrel cortex areas of behaviorally-engaged whisker representations, in their zones of overlap. While the overall areas of representation expanded dramatically, the domains of exclusive principal whisker responses were virtually identical in enriched vs normal rats and were significantly smaller than either group in roughness discrimination-trained rats. When animals were trained or exposed to enriched environments with the three whiskers arrayed in an are or row, very equivalent overlaps in representations were recorded across their greatly-enlarged whisker representation zones. This equivalence in distortion in these behavioral preparations is in contradistinction to the normal rat, where overlap is strongly biased only along rows, probably reflecting the establishment of different relations with the neighboring cortical columns. Overall, plasticity phenomena are argued to be consistent with the predictions of competitive Hebbian network plasticity.

Non-homogeneous spatial configuration of vibrissae cortical representation in layer IV of the barrel somatosensory cortex.

In the present experiments we studied exclusive and overlapping cortical representational areas of the vibrissae in layer IV cells, across the entire barrel subfield of the rat somatosensory cortex, looking for evidences that would challenge the present assumptions of homogeneity and symmetry among cortical columns in this sensorial system. Our main findings were that in layer IV of the rat barrel cortex: A) Size of vibrissae cortical representational areas (X=0.4174mm(2); SD=0.025) was not homogeneous, vibrissae in dorsal rows (A-B) had significantly smaller areas than those in ventral rows (D-E), a pattern that repeated itself in ares 1-4. B) This difference arises from vibrissal representational overlap, and not from variations in exclusive zones, which are surprisingly homogeneous in size across the barrel cortex (X=0.079mm(2); SD=0.0075); C) The extent of overlapping cortical areas varied systematically, with intra-row overlapping areas having a predominant bias (71.4% of total overlapping) independent of area sizes. Accordingly, vibrissae shared receptive fields with an average of 1.15 vibrissae in the same row and 0.38 in the same are. Barrel cortex has been viewed operationally as a conglomerate of essentially homogenous cortical columns that interact equivalently in the are and row dimensions. Our simple but global cortical reconstructions show that this predominant view should be revised. We postulate that the vibrissae/barrels spatial disposition in rows and ares has a relevant functional meaning, related to different sensory capabilities.