Choosing our words: Neural mechanisms supporting cognitive control during language processing

When we speak, we must constantly retrieve and select words in the face of multiple competing alternatives. Previous research has left many questions unanswered about how we achieve these fundamental cognitive control processes. This dissertation contributes to answering these questions at three levels. First, using well-controlled tasks and measures, we ask what specific aspects of language production drive cognitive control demands, as indexed by slower RTs to produce a verbal response. Second, we apply these unconfounded measures to fMRI experiments, to ask what neural substrates support cognitive control during language production. Third, we ask how these brain areas support cognitive control processes, by first simulating possible mechanisms in a neural network model and then empirically testing model predictions using pharmacological and clinical methods. In sum, the dissertation research suggests that cognitive control is needed during language production when responses compete with alternative task-relevant response options (underdetermined selection), compete with prepotent responses (prepotent selection), or are difficult to retrieve from semantic memory (controlled retrieval), and these demands interact both behaviorally and neurally. Shared neural substrates in left ventrolateral prefrontal cortex (VLPFC) support both underdetermined selection and controlled retrieval, while left VLPFC is not activated by prepotent selection demands. In contrast, an area of left dorsolateral prefrontal cortex (DLPFC) is sensitive to both underdetermined and prepotent competition. Neural network simulations suggest that competitive lateral inhibition in VLPFC is key for underdetermined selection, while other mechanisms subserved by VLPFC support controlled retrieval, and top-down biasing from DLPFC is critical for prepotent selection. As predicted by the model, increased inhibition under the GABA agonist midazolam improved selection, while anxiety (linked to reduced GABAergic function) was associated with impaired selection and reduced engagement of left VLPFC during selection. These findings enable a synthesis and reinterpretation of prior evidence, and suggest that language production is affected by both selection and retrieval mechanisms subserved by left VLPFC and DLPFC, and these processes interact in meaningful ways. Better understanding these fundamental aspects of language production may ultimately have implications for better understanding and treating impairments associated with prefrontal damage, as well as anxiety and depression

Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science

Less-structured time in children's daily lives predicts self-directed executive functioning.

Executive functions (EFs) in childhood predict important life outcomes. Thus, there is great interest in attempts to improve EFs early in life. Many interventions are led by trained adults, including structured training activities in the lab, and less-structured activities implemented in schools. Such programs have yielded gains in children's externally-driven executive functioning, where they are instructed on what goal-directed actions to carry out and when. However, it is less clear how children's experiences relate to their development of self-directed executive functioning, where they must determine on their own what goal-directed actions to carry out and when. We hypothesized that time spent in less-structured activities would give children opportunities to practice self-directed executive functioning, and lead to benefits. To investigate this possibility, we collected information from parents about their 6-7 year-old children's daily, annual, and typical schedules. We categorized children's activities as "structured" or "less-structured" based on categorization schemes from prior studies on child leisure time use. We assessed children's self-directed executive functioning using a well-established verbal fluency task, in which children generate members of a category and can decide on their own when to switch from one subcategory to another. The more time that children spent in less-structured activities, the better their self-directed executive functioning. The opposite was true of structured activities, which predicted poorer self-directed executive functioning. These relationships were robust (holding across increasingly strict classifications of structured and less-structured time) and specific (time use did not predict externally-driven executive functioning). We discuss implications, caveats, and ways in which potential interpretations can be distinguished in future work, to advance an understanding of this fundamental aspect of growing up

Prefrontal Cortical Response to Conflict during Semantic and Phonological Tasks

Debates about the function of the prefrontal cortex are as old as the field of neuropsychology—often dated to Paul Broca’s seminal work. Theories of the functional organization of the prefrontal cortex can be roughly divided into those that describe organization by process and those that describe organization by material. Recent studies of the function of the posterior, left inferior frontal gyrus (pLIFG) have yielded two quite different interpretations: One hypothesis holds that the pLIFG plays a domain-specific role in phonological processing, whereas another hypothesis describes a more general function of the pLIFG in cognitive control. In the current study, we distinguish effects of increasing cognitive control demands from effects of phonological processing. The results support the hypothesized role for the pLIFG in cognitive control, and more task-specific roles for posterior areas in phonology and semantics. Thus, these results suggest an alternative explanation of previously reported phonology-specific effects in the pLIFG

When Does Stress Help or Harm? The Effects of Stress Controllability and Subjective Stress Response on Stroop Performance

The ability to engage in goal-directed behavior despite exposure to stress is critical to resilience. Questions of how stress can impair or improve behavioral functioning are important in diverse settings, from athletic competitions to academic testing. Previous research suggests that controllability is a key factor in the impact of stress on behavior: learning how to control stressors buffers people from the negative effects of stress on subsequent cognitively demanding tasks. In addition, research suggests that the impact of stress on cognitive functioning depends on an individual’s response to stressors: moderate responses to stress can lead to improved performance while extreme (high or low) responses can lead to impaired performance. The present studies tested the hypothesis that (1) learning to behaviorally control stressors leads to improved performance on a test of general executive functioning, the color-word Stroop, and that (2) this improvement emerges specifically for people who report moderate (subjective) responses to stress. Experiment 1: Stroop performance, measured before and after a stress manipulation, was compared across groups of undergraduate participants (n = 109). People who learned to control a noise stressor and received accurate performance feedback demonstrated reduced Stroop interference compared with people exposed to uncontrollable noise stress and feedback indicating an exaggerated rate of failure. In the group who learned behavioral control, those who reported moderate levels of stress showed the greatest reduction in Stroop interference. In contrast, in the group exposed to uncontrollable events, self-reported stress failed to predict performance. Experiment 2: In a second sample (n = 90), we specifically investigated the role of controllability by keeping the rate of failure feedback constant across groups. In the group who learned behavioral control, those who reported moderate levels of stress showed the greatest Stroop improvement. Once again, this pattern was not demonstrated in the group exposed to uncontrollable events. These results suggest that stress controllability and subjective response interact to affect high-level cognitive abilities. Specifically, exposure to moderate, controllable stress benefits performance, but exposure to uncontrollable stress or having a more extreme response to stress tends to harm performance. These findings may provide insights on how to leverage the beneficial effects of stress in a range of settings

Maternal Depressive Symptoms Predict General Liability in Child Psychopathology

Objective: The current study examines how maternal depressive symptoms relate to child psychopathology when structured via the latent bifactor model of psychopathology, a new organizational structure of psychopathological symptoms consisting of a general common psychopathology factor (p-factor) and internalizing- and externalizing-specific risk. Method: Maternal report of depressive symptoms (Beck Depression Inventory – II) and child psychopathological symptoms (Child Behavior Checklist and Children’s Behavior Questionnaire) were provided by 554 mother-child pairs. Children in the sample were 7.7 years old on average (SD = 1.35, range = 5–11 years), and were 49.8% female, 46% Latinx, and 67% White, 6% Black, 5% Asian/Pacific Islander, and 21% multiracial. Results: Maternal depressive symptoms were positively associated with the child p-factor but not with the internalizing- or externalizing-specific factors. We did not find evidence of sex/gender or race/ethnicity moderation when using latent factors of psychopathology. Consistent with past research, maternal depressive symptoms were positively associated with internalizing and externalizing composite scores on the Child Behavior Checklist. Conclusions: Findings suggest that maternal depressive symptoms are associated with transdiagnostic risk for broad child psychopathology (p-factor). Whereas the traditional Achenbach-style approach of psychopathological assessment suggests that maternal depressive symptoms are associated with both child internalizing and externalizing problems, the latent bifactor model suggests that these associations may be accounted for by risk pathways related to the p-factor rather than internalizing or externalizing specific risk. We discuss clinical and research implications of using a latent bifactor structure of psychopathology to understand how maternal depression may impact children’s mental health

Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates

Genome sequences of four cluster P mycobacteriophages

Four bacteriophages infecting Mycobacterium smegmatis mc2155 (three belonging to subcluster P1 and one belonging to subcluster P2) were isolated from soil and sequenced. All four phages are similar in the left arm of their genomes, but the P2 phage differs in the right arm. All four genomes contain features of temperate phages

A short educational intervention diminishes causal illusions and specific paranormal beliefs in undergraduates

Cognitive biases such as causal illusions have been related to paranormal and pseudoscientific beliefs and, thus, pose a real threat to the development of adequate critical thinking abilities. We aimed to reduce causal illusions in undergraduates by means of an educational intervention combining training-in-bias and training-in-rules techniques. First, participants directly experienced situations that tend to induce the Barnum effect and the confirmation bias. Thereafter, these effects were explained and examples of their influence over everyday life were provided. Compared to a control group, participants who received the intervention showed diminished causal illusions in a contingency learning task and a decrease in the precognition dimension of a paranormal belief scale. Overall, results suggest that evidence-based educational interventions like the one presented here could be used to significantly improve critical thinking skills in our students