Thinking theta and alpha: Mechanisms of intuitive and analytical reasoning.

Humans have a unique ability to engage in different modes of thinking. Intuitive thinking (coined System 1, see Kahneman, 2011) is fast, automatic, and effortless whereas analytical thinking (coined System 2) is slow, contemplative, and effortful. We extend seminal pupillometry research examining these modes of thinking by using electroencephalography (EEG) to decipher their respective underlying neural mechanisms. We demonstrate that System 1 thinking is characterized by an increase in parietal alpha EEG power reflecting autonomic access to long-term memory and a release of attentional resources whereas System 2 thinking is characterized by an increase in frontal theta EEG power indicative of the engagement of cognitive control and working memory processes. Consider our results in terms of an example - a child may need cognitive control and working memory when contemplating a mathematics problem yet an adult can drive a car with little to no attention by drawing on easily accessed memories. Importantly, the unravelling of intuitive and analytical thinking mechanisms and their neural signatures will provide insight as to how different modes of thinking drive our everyday lives.

Factors Predicting Length of Hospital Stay and Extended Care Facility Admission After Hindfoot Arthrodesis Procedures.

Delayed identification of patients requiring admission to extended care facilities (ECFs) can lead to greater healthcare costs through an increased length of hospital stay (LOHS). Previous studies of hip and knee arthroplasty identified factors associated with a likely discharge to an ECF. These issues have not been extensively studied for major hindfoot procedures. We conducted a retrospective review of 198 cases treated during a 3-year period to identify the risk factors for an extended LOHS and ECF admission after ankle arthrodesis, triple arthrodesis, pantalar arthrodesis, and subtalar arthrodesis. The primary outcomes were LOHS and ECF admission. The independent predictors included age, sex, body mass index, housing status, American Society of Anesthesiologists class, diabetes and/or diabetic neuropathy, health insurance, fixation type, and perioperative infection. Stepwise multiple regression analysis was used to determine which variables were related to a longer LOHS. Nonparametric discriminant function analysis was used to identify the preoperative factors that best predicted ECF admission. A longer LOHS was significantly related to postoperative ECF admission, Centers for Medicare and Medicaid Services (CMS) insurance, diabetic neuropathy, external fixation, and infection. ECF admission was required for 34 of 198 patients (17.2%). Discriminant analysis found that older age, living alone, external fixation, and CMS insurance predicted a greater probability of ECF admission. The function accurately classified 94% of ECF admissions and 80% of non-ECF admission patients. ECF admission and CMS insurance extended the LOHS, likely owing to the administrative process of arranging an ECF discharge. If externally validated, the function we have derived could provide preoperative identification of likely ECF discharge candidates and reduce costs by shortening the LOHS.

The Assessment of Blood Loss During Total Knee Arthroplasty When Comparing Intravenous vs Intracapsular Administration of Tranexamic Acid.

BACKGROUND: Administration of tranexamic acid topically and intravenously has demonstrated effectiveness in decreasing blood loss and transfusion rates. METHODS: We randomized 131 patients undergoing primary total knee arthroplasty to receive either intracapsular (69) or intravenous tranexamic acid (62). Postoperative blood loss was calculated using the formula derived by Nadler et al. The number of units transfused was recorded, as well as length of hospital stay. RESULTS: We found no statistically significant difference on calculated blood loss (postoperative day [POD] 1: 624 ± 326 vs 644 ± 292; P = .71, POD 2: 806 ± 368 vs 835 ± 319; P = .64, and POD 3: 1076 ± 419 vs 978 ± 343; P = .55). There was no difference in number of blood transfusions, length of stay, or complications. CONCLUSION: Intracapsular tranexamic acid is not inferior to intravenous tranexamic acid in decreasing blood loss and blood transfusion rate in primary total knee arthroplasty.

Phasic Stimulation of Dopaminergic Neurons of the Lateral Substantia Nigra Increases Open Field Exploratory Behaviour and Reduces Habituation Over Time.

Transient nigrostriatal dopaminergic signalling is well known for its role in reinforcement learning and increasingly so for its role in the initiation of voluntary movement. However, how transient bursts of dopamine modulate voluntary movement remains unclear, likely due to the heterogeneity of the nigrostriatal system, the focus of optogenetic studies on locomotion at sub-sec time intervals, and the overlapping roles of phasic dopamine in behaviour and novelty signalling. In this study we investigated how phasic activity in the lateral substantia nigra pars compacta (lateral SNc) over time affects voluntary behaviours during exploration. Using a transgenic mouse model of both sexes expressing channelrhodopsin (ChR2) in dopamine transporter-expressing cells, we stimulated the lateral SNc while mice explored an open field over two consecutive days. We found that phasic activation of the lateral SNc induced an increase in exploratory behaviours including horizontal movement activity, locomotion initiation, and rearing specifically on the first open field exposure, but not on the second day. In addition, stimulated animals did not habituate to the same extent as their ChR2-negative counterparts, as indicated by a lack of decrease in baseline activity. These findings suggest that rather than prompting voluntary movement in general, phasic nigrostriatal dopamine prompts context-appropriate behaviours. In addition, dopamine signalling that modulates movement acts over longer timescales than the transient signal, affecting behaviour even after the signal has ended.

Stabilizing expectations when shifting from analytical to intuitive reasoning: The role of prediction errors in reasoning.

As humans, we rely on intuitive reasoning for most of our decisions. However, when there is a novel or atypical decision to be made, we must rely on a slower and more deliberative thought process-analytical reasoning. As we gain experience with these novel or atypical decisions, our reasoning shifts from analytical to intuitive, which parallels a reduction in the need for cognitive control. Here, we sought to confirm this claim by employing electroencephalographic (EEG) measures of cognitive control as participants performed a simple perceptual decision-making task. Specifically, we had participants categorize "blobs" into families based on their visual attributes so we could examine how their reasoning changed with learning. In a key manipulation, halfway through the experiment we introduced novel blob families to categorize, thus temporarily increasing the need for analytical reasoning (i.e., cognitive control). Congruent with past research, we focused our EEG analyses on frontal theta activity as it has been linked to cognitive control and analytical thinking. As hypothesized, we found a transition from analytical to intuitive decision-making systems with learning as indexed by a decrease in frontal theta power. Further, when the novel blobs were introduced at the midpoint of the experiment, we found that decisions about these stimuli recruited analytical reasoning as indicated by increased theta power in comparison to decisions about well-practiced stimuli. We propose our findings to reflect prediction errors to decision demands-a monitoring process that determines whether our expectations of demands are met. Shifting from analytical to intuitive reasoning thus reflects the stabilization of our expectations of decision demands, which can be violated with unexpected demands when encountering novel stimuli.

Unsedated peroral wireless pH capsule placement vs. standard pH testing: a randomized study and cost analysis.

BACKGROUND: Wireless capsule pH-metry (WC) is better tolerated than standard nasal pH catheter (SC), but endoscopic placement is expensive. AIMS: to confirm that non-endoscopic peroral manometric placement of WC is as effective and better tolerated than SC and to perform a cost analysis of the available esophageal pH-metry methods. METHODS: Randomized trial at 2 centers. Patients referred for esophageal pH testing were randomly assigned to WC with unsedated peroral placement or SC after esophageal manometry (ESM). Primary outcome was overall discomfort with pH-metry. Costs of 3 different pH-metry strategies were analyzed: 1) ESM + SC, 2) ESM + WC and 3) endoscopically placed WC (EGD + WC) using publicly funded health care system perspective. RESULTS: 86 patients (mean age 51 ± 2 years, 71% female) were enrolled. Overall discomfort score was less in WC than in SC patients (26 ± 4 mm vs 39 ± 4 mm VAS, respectively, p = 0.012) but there were no significant group differences in throat, chest, or overall discomfort during placement. Overall failure rate was 7% in the SC group vs 12% in the WC group (p = 0.71). Per patient costs ($Canadian) were $1475 for EGD + WC, $1014 for ESM + WC, and $906 for ESM + SC. Decreasing the failure rate of ESM + WC from 12% to 5% decreased the cost of ESM + WC to $991. The ESM + SC and ESM + WC strategies became equivalent when the cost of the WC device was dropped from $292 to $193. CONCLUSIONS: Unsedated peroral WC insertion is better tolerated than SC pH-metry both overall and during placement. Although WC is more costly, the extra expense is partially offset when the higher patient and caregiver time costs of SC are considered. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01364610.

Using EEG to decode semantics during an artificial language learning task.

BACKGROUND: As we learn a new nonnative language (L2), we begin to build a new map of concepts onto orthographic representations. Eventually, L2 can conjure as rich a semantic representation as our native language (L1). However, the neural processes for mapping a new orthographic representation to a familiar meaning are not well understood or characterized. METHODS: Using electroencephalography and an artificial language that maps symbols to English words, we show that it is possible to use machine learning models to detect a newly formed semantic mapping as it is acquired. RESULTS: Through a trial-by-trial analysis, we show that we can detect when a new semantic mapping is formed. Our results show that, like word meaning representations evoked by a L1, the localization of the newly formed neural representations is highly distributed, but the representation may emerge more slowly after the onset of the symbol. Furthermore, our mapping of word meanings to symbols removes the confound of the semantics to the visual characteristics of the stimulus, a confound that has been difficult to disentangle previously. CONCLUSION: We have shown that the L1 semantic representation conjured by a newly acquired L2 word can be detected using decoding techniques, and we give the first characterization of the emergence of that mapping. Our work opens up new possibilities for the study of semantic representations during L2 learning.

The ERP, frequency, and time-frequency correlates of feedback processing: Insights from a large sample study.

Human learning, at least in part, appears to be dependent on the evaluation of how outcomes of our actions align with our expectations. Over the past 23 years, electroencephalography (EEG) has been used to probe the neural signatures of feedback processing. Seminal work demonstrated a difference in the human event-related potential (ERP) dependent on whether people were processing correct or incorrect feedback. Since then, these feedback evoked ERPs have been associated with reinforcement learning and conflict monitoring, tied to subsequent behavioral adaptations, and shown to be sensitive to a wide range of factors (e.g., Parkinson's disease). Recently, research has turned to frequency decomposition techniques to examine how changes in the EEG power spectra are related to underlying learning mechanisms. Although the literature on the neural correlates of feedback processing is vast, there are still methodological discrepancies and differences in results across studies. Here, we provide reference results and an investigation of methodological considerations for the ERP (reward positivity) and frequency (delta and theta power) correlates of feedback evaluation with a large sample size. Specifically, participants (n = 500) performed a two-armed bandit task while we recorded EEG. Our findings provide key information about the data characteristics and relationships that exist between the neural signatures of feedback evaluation. Additionally, we conclude with selected methodological recommendations for standardization of future research. All data and scripts are freely provided to facilitate open science.

Dissociated neural signals of conflict and surprise in effortful decision Making: Theta activity reflects surprise while alpha and beta activity reflect conflict.

What makes a decision difficult? Two key factors are conflict and surprise: conflict emerges with multiple competing responses and surprise occurs with unexpected events. Conflict and surprise, however, are often thought of as parsimonious accounts of decision making rather than an integrated narrative. We sought to determine whether conflict and/or surprise concurrently or independently elicit effortful decision making. Participants made a series of diagnostic decisions from physiological readings while electroencephalographic (EEG) data were recorded. To induce conflict and surprise, we manipulated task difficulty by varying the distance between a presented physiological reading and the category border that separated the two diagnoses. Whereas frontal theta oscillations reflected surprise - when presented readings were far from the expected mean, parietal alpha and beta oscillations indicated conflict - when readings were near the category border. Our findings provide neural evidence that both conflict and surprise engage cognitive control to employ effort in decision making.

What happens when right means wrong? The impact of conflict arising from competing feedback responses.

Humans often rely on feedback to learn. Indeed, in learning the difference between feedback and an expected outcome is computed to inform future actions. Further, recent work has found that reward and feedback have a unique role in modulating conflict processing and cognitive control. However, it is still not clear how conflict, especially concerning the processing and evaluation of feedback, impacts learning. To address this, we examined the effects of feedback competition on feedback evaluation in a reinforcement learning task. Specifically, we had participants play a simple two-choice gambling game while electroencephalographic (EEG) data were recorded. On half of the experiment blocks, we reversed the meaning of performance feedback for each trial from its prepotent meaning to induce response conflict akin to the Stroop effect (e.g., '✓' meant incorrect). Behaviourally, we found that participants' accuracy was reduced as a result of incongruent feedback. Paralleling this, an analysis of our EEG revealed that incongruent feedback resulted in a reduction in amplitude of the reward positivity and the P300, components of the human event-related brain potential implicated in reward processing. Our results demonstrate the negative impact of conflict on feedback evaluation and the impact of this on subsequent performance.

The impact of wellness on neural learning systems.

Over the past 20 years there has been an increasing push for people to achieve or maintain "wellness" - a state in which one has not only physical but also mental and social well-being. While it may seem obvious that maintaining a state of wellness is beneficial, little research has been done to probe how maintaining a state of wellness impacts our brain. Here, we specifically examined the impact of wellness on a neural system within the medial-frontal cortex responsible for human reinforcement learning. Sixty-two undergraduate students completed the Perceived Wellness Survey after which they completed a computer-based learnable gambling game while electroencephalographic data were recorded. Within the game, participants were presented with a series of choices that either led to financial gains or losses. An analysis of our behavioral data indicated that participants were able to learn the underlying structure of the gambling game given that we observed improvements in performance. Concurrent with this, we observed an electroencephalographic response evoked by the evaluation of gambling outcomes - the reward positivity. Importantly, we found significant relationships between several aspects of wellness and the amplitude of the reward positivity. Given that the reward positivity is thought to reflect the function of a reinforcement learning system within the medial-frontal cortex, our results suggest that wellness impacts neural function - in this instance one of the systems responsible for human learning.

Passively learned spatial navigation cues evoke reinforcement learning reward signals.

Since the suggestion by Tolman (1948) that both rodents and humans create cognitive maps during navigation, the specifics of how navigators learn about their environment has been mired in debate. One facet of this debate is whether or not the creation of cognitive maps - also known as allocentric navigation - involves reinforcement learning. Here, we demonstrate a role for reinforcement learning during allocentric navigation using event-related brain potentials (ERPs). In the present experiment, participants navigated in a virtual environment that allowed the use of three different navigation strategies (allocentric, egocentric-response, & egocentric-cue), in which their goal was to locate and remember a hidden platform. Following the navigation phase of the experiment, participants were shown "cue images" representative of the three navigation strategies. Specifically, we examined whether or not these passively learned strategy images elicited a reward positivity - an ERP component associated with reinforcement learning and the anterior cingulate cortex. We found that when allocentric navigators were shown previously learned cues predicting the goal location a reward positivity was elicited. The present findings demonstrate that allocentric navigational cues carry long-term value after navigation and lend support to the claim that reinforcement learning plays a role in the acquisition of allocentric navigation and thus the generation of cognitive maps.

Electroencephalography correlates of transcranial direct-current stimulation enhanced surgical skill learning: A replication and extension study.

Transcranial direct-current stimulation (tDCS), an increasingly applied form of non-invasive brain stimulation, can augment the acquisition of motor skills. Motor learning investigations of tDCS are limited to simple skills, where mechanisms are increasingly understood. Investigations of meaningful, complex motor skills possessed by humans, such as surgical skills, are limited. This replication and extension of our previous findings used electroencephalography (EEG) to determine how tDCS and complex surgical training alters electrical activity in the sensorimotor network to enhance complex surgical skill acquisition. In twenty-two participants, EEG was recorded during baseline performance of simulation-based laparoscopic surgical skills. Participants were randomized to receive 20 min of primary motor cortex targeting anodal tDCS or sham concurrent to 1 h of surgical skill training. EEG was reassessed following training, during a post-training repetition of the surgical tasks. Our results replicated our previous study suggesting that compared to sham, anodal tDCS enhanced the acquisition of unimanual surgical skill. Surgical training modulated delta frequency band activity in sensorimotor regions. Next, the performance of unimanual and bimanual skills evoked unique EEG profiles, primarily within the beta frequency-band in parietal regions. Finally, tDCS-paired surgical training independently modulated delta and alpha frequency-bands in sensorimotor regions. Application of tDCS during surgical skill training is feasible, safe and tolerable. In conclusion, we are the first to explore electrical brain activity during performance of surgical skills, how electrical activity may change during surgical training and how tDCS alters the brain to enhance skill acquisition. The results provide preliminary evidence of neural markers that can be targeted by neuromodulation to optimize complex surgical training.

Chasing the zone: Reduced beta power predicts baseball batting performance.

Mental state prior to sports skill execution is related to subsequent performance. For example, relationships between pre-performance electroencephalogram (EEG) power and subsequent movement outcomes in golf putting, pistol shooting, and basketball free throw shooting have been previously reported. With that said, the existing body of research examining the pre-performance EEG - performance relationship has been focused on the execution of internally as opposed to externally-paced motor skills. Given that the execution of internally and externally-paced movements are dependent on different neural pathways, in the present study we examined whether or not pre-performance EEG power predicted ensuing performance of an externally-paced motor skill - baseball batting. Sixty-seven baseball players had EEG data recorded for 120 s prior to batting practice. Performance was assessed by three expert coaches and the accuracy of coach performance ratings was verified via Generalizability Theory. An analysis of our data revealed an inverse relationship between frontal EEG power in the beta range and subsequent batting performance - reduced beta power was associated with better batting performance whereas increased beta power was associated with worse batting performance. Our results are in line with prior research that has demonstrated a relationship between increased EEG power in the beta range and the subsequent commitment of motor errors in addition to the aforementioned work examining pre-performance EEG and the execution of internally-paced motor skills.

Immune Repertoire Sequencing Using Molecular Identifiers Enables Accurate Clonality Discovery and Clone Size Quantification.

Unique molecular identifiers (MIDs) have been demonstrated to effectively improve immune repertoire sequencing (IR-seq) accuracy, especially to identify somatic hypermutations in antibody repertoire sequencing. However, evaluating the sensitivity to detect rare T cells and the degree of clonal expansion in IR-seq has been difficult due to the lack of knowledge of T cell receptor (TCR) RNA molecule copy number and a generalized approach to estimate T cell clone size from TCR RNA molecule quantification. This limited the application of TCR repertoire sequencing (TCR-seq) in clinical settings, such as detecting minimal residual disease in lymphoid malignancies after treatment, evaluating effectiveness of vaccination and assessing degree of infection. Here, we describe using an MID Clustering-based IR-Seq (MIDCIRS) method to quantitatively study TCR RNA molecule copy number and clonality in T cells. First, we demonstrated the necessity of performing MID sub-clustering to eliminate erroneous sequences. Further, we showed that MIDCIRS enables a sensitive detection of a single cell in as many as one million naïve T cells and an accurate estimation of the degree of T cell clonal expression. The demonstrated accuracy, sensitivity, and wide dynamic range of MIDCIRS TCR-seq provide foundations for future applications in both basic research and clinical settings.

Alcohol hangover impacts learning and reward processing within the medial-frontal cortex.

It is common knowledge that alcohol intoxication impairs motor coordination, judgment, and decision making. Indeed, an abundance of literature links intoxication to impaired cognitive control that leads to accidents and injury. A broadening body of research, however, suggests that the impact of alcohol may continue beyond the point of intoxication and into the period of alcohol hangover. Here, we examined differences in the amplitude of reward positivity-a component of the human ERP associated with learning-between control and hangover participants. During performance of a learnable gambling task, we found a reduction in the reward positivity during alcohol hangover. Additionally, participants experiencing alcohol hangover demonstrated reduced performance in the experimental task in comparison to their nonhangover counterparts. Our results suggest that the neural systems that underlie performance monitoring and reward-based learning are impaired during alcohol hangover.

High-throughput determination of the antigen specificities of T cell receptors in single cells.

We present tetramer-associated T-cell receptor sequencing (TetTCR-seq) to link T cell receptor (TCR) sequences to their cognate antigens in single cells at high throughput. Binding is determined using a library of DNA-barcoded antigen tetramers that is rapidly generated by in vitro transcription and translation. We applied TetTCR-seq to identify patterns in TCR cross-reactivity with cancer neoantigens and to rapidly isolate neoantigen-specific TCRs with no cross-reactivity to the wild-type antigen.

The application of reward learning in the real world: Changes in the reward positivity amplitude reflect learning in a medical education context.

Evidence ranging from behavioural adaptations to neurocognitive theories has made significant advances into our understanding of feedback-based learning. For instance, over the past twenty years research using electroencephalography has demonstrated that the amplitude of a component of the human event-related brain potential - the reward positivity - appears to change with learning in a manner predicted by reinforcement learning theory (Holroyd and Coles, 2002; Sutton and Barto, 1998). However, while the reward positivity (also known as the feedback related negativity) is well studied, whether the component reflects an underlying learning process or whether it is simply sensitive to feedback evaluation is still unclear. Here, we sought to provide support that the reward positivity is reflective of an underlying learning process and further we hoped to demonstrate this in a real-world medical education context. In the present study, students with no medical training viewed a series of patient cards that contained ten physiological readings relevant for diagnosing liver and biliary disease types, selected the most appropriate diagnostic classification, and received feedback as to whether their decisions were correct or incorrect. Our behavioural results revealed that our participants were able to learn to diagnose liver and biliary disease types. Importantly, we found that the amplitude of the reward positivity diminished in a concomitant manner with the aforementioned behavioural improvements. In sum, our data support theoretical predictions (e.g., Holroyd and Coles, 2002), suggest that the reward positivity is an index of a neural learning system, and further validate that this same system is involved in learning across a wide range of contexts.

Flexor Hallucis Longus Tendon Transfer Fixation.

INTRODUCTION: Flexor hallucis longus (FHL) tendon transfer to the calcaneus is commonly used in the surgical treatment of chronic Achilles tendinopathy. This study assesses the integrity of FHL tendon biotenodesis screw fixation with respect to 2 variables: incorporation of a terminal whipstitch and tunnel depth. MATERIALS AND METHODS: A total of 60 fresh-frozen cadaver FHL tendons and 28 calcanei were harvested for analysis in 4 sets of fixation constructs; 14 whipstitched tendons were compared against their nonwhipstitched paired tendon via pull-out strength load testing, and 16 tendon pairs were randomized for fixation in either a full-depth tunnel (bicortical) or a 25-mm partial tunnel (unicortical). All comparisons were carried out in native bone and synthetic models. RESULTS: Whipstitched tendons demonstrated significantly stronger mean clinical load (253.68 vs 177.24 N, P = .008) and maximum load to failure (294.31N vs 194.57 N, P = .001) compared with the nonwhipstitched tendons in synthetic bone. There were no statistical differences in mean clinical load (200.96 vs 228.31 N, P = .63) and maximum load to failure (192.69 vs 217.74 N, P = .73) between full and partial tunnel groups. There were no significant differences found in trials carried out in cadaveric bone. CONCLUSION: Use of a terminal whipstitch achieves greater fixation strength in FHL tendon biotenodesis transfers. Complete and partial tunnel constructs are equivocal in their pull-out strength. Data produced in a homogeneous bone substitute model demonstrate the biomechanical superiority of the whipstitch as well as the noninferiority of the partial tunnel technique. LEVELS OF EVIDENCE: Level IIb.