Chronic Stress Effects on Prefrontal Cortical Structure and Function

Stressful life events have been implicated clinically in the pathogenesis of major depression, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of depression are associated with structural and functional abnormalities in the prefrontal cortex. In three parallel rodent and human neuroimaging studies, this project assessed the effects of chronic stress on prefrontal cortical structure and function and the behavioral correlates of these changes. The first study used fMRI to elucidate the precise computational contributions of frontoparietal circuitry to attentional control in human subjects, using a task that could be adapted for rats. The results confirmed that the contributions of dorsolateral frontoparietal areas to visual attentional shifts could be dissociated from the regulatory influences of more ventrolateral areas on stimulus/response mappings, in a manner consistent with studies in animal models. They also indicated that anterior cingulate and posterior parietal cortex may act in concert to detect dissociable forms of information processing conflicts and signal to dorsolateral prefrontal cortex the need for increased attentional control. Stress-induced alterations in these regions and in the connections between them may therefore contribute to attentional impairments. The second study tested this hypothesis in rats by examining whether chronic stress effects on medial prefrontal (mPFC) and orbitofrontal (OFC) dendritic morphology underlie impairments in the behaviors that they subserve. Chronic stress induced a selective impairment in attentional control and a corresponding retraction of apical dendritic arbors in mPFC. By contrast, stress did not adversely affect reversal learning or OFC dendritic arborization. These results suggest that prefrontal dendritic remodeling may underlie the attentional deficits that are symptomatic of stress-related mental illness. The third study was designed to extend these findings to human subjects, using the techniques developed in Study 1. Accordingly, chronic stress predicted selective attentional impairments and alterations in prefrontal functional coupling that were reversible after four weeks. Together, these studies outline in broad strokes a mechanistic model by which chronic stress may predispose susceptible persons to the attentional impairments that are characteristic of major depression. Future studies will assess the roles of serotonin and neurotrophins in mediating these changes

Individual differences in visual perception capacity and related brain morphology

Limited capacity for perception results in various phenomena of inattentional blindness in task conditions that load perceptual capacity. These effects have been extensively studied under the load theory framework, with numerous demonstrations spanning a wide variety of perceptual load manipulations. Research also established contrasting effects of loading perception versus cognitive control functions (e.g. working memory). The convergence of findings across different manipulations of perceptual load together with the contrasting effects of cognitive control load suggests a generalised capacity for perception, which is distinct from general cognitive capacity. The purpose of this thesis was to examine this hypothesis further, using an individual differences approach and relating traditional visual perception and awareness paradigms to the phenomenon of subitizing: the ability to detect a limited number of items in parallel from a brief exposure that has traditionally been studied within the enumeration literature. The research first extended perceptual load effects to measures of unattended processing in an enumeration paradigm, demonstrating that distractor effects are only found within subitizing capacity but not in set sizes that exceed capacity (Chapter 2). A series of individual differences experiments then revealed significant correlations between tasks involving subitizing, motion tracking, ‘change blindness’ and ‘inattentional blindness’. These relationships were furthermore established to withstand controls for non-perceptual factors, establishing perceptual capacity as distinct from working memory capacity or general cognitive effort (Chapters 3-4). Finally, voxel-based morphometry analyses of structural brain images established distinct correlates of grey matter density for perceptual capacity across tasks (Chapter 5). Taken together, the results of this thesis establish individual differences in perceptual capacity across a diverse range of paradigms and stimuli, demonstrating a common, general capacity limit for perception which correlates with individual differences in performance and grey-matter density and is independent from other cognitive constructs such as number estimation abilities and executive working memory

Domain-specific and domain-general processes underlying metacognitive judgments

Metacognition and self-awareness are commonly assumed to operate as global capacities. However, there have been few attempts to test this assumption across multiple cognitive domains and metacognitive evaluations. Here, we assessed the covariance between “online” metacognitive processes, as measured by decision confidence judgments in the domains of perception and memory, and error awareness in the domain of attention to action. Previous research investigating metacognition across task domains have not matched stimulus characteristics across tasks raising the possibility that any differences in metacognitive accuracy may be influenced by local task properties. The current experiment measured metacognition in perceptual, memorial and attention tasks that were closely matched for stimulus characteristics. We found that metacognitive accuracy across the three tasks was dissociated suggesting that domain specific networks support an individual's capacity for accurate metacognition. This finding was independent of objective performance, which was controlled using a staircase procedure. However, response times for metacognitive judgments and error awareness were associated suggesting that shared mechanisms determining how these meta-level evaluations unfold in time may underlie these different types of decision. In addition, the relationship between these laboratory measures of metacognition and reports of everyday functioning from participants and their significant others (informants) was investigated. We found that informant reports, but not self reports, predicted metacognitive accuracy on the perceptual task and participants who underreported cognitive difficulties relative to their informants also showed poorer metacognitive accuracy on the perceptual task. These results are discussed in the context of models of metacognitive regulation and neuropsychological evidence for dissociable metacognitive systems. The potential for the refinement of metacognitive assessment in clinical populations is also discussed

Improving Sentence Comprehension Post-Stroke Using Neuroimaging and Neuropsychological Approaches

abstract: Cognitive deficits often accompany language impairments post-stroke. Past research has focused on working memory in aphasia, but attention is largely underexplored. Therefore, this dissertation will first quantify attention deficits post-stroke before investigating whether preserved cognitive abilities, including attention, can improve auditory sentence comprehension post-stroke. In Experiment 1a, three components of attention (alerting, orienting, executive control) were measured in persons with aphasia and matched-controls using visual and auditory versions of the well-studied Attention Network Test. Experiment 1b then explored the neural resources supporting each component of attention in the visual and auditory modalities in chronic stroke participants. The results from Experiment 1a indicate that alerting, orienting, and executive control are uniquely affected by presentation modality. The lesion-symptom mapping results from Experiment 1b associated the left angular gyrus with visual executive control, the left supramarginal gyrus with auditory alerting, and Broca’s area (pars opercularis) with auditory orienting attention post-stroke. Overall, these findings indicate that perceptual modality may impact the lateralization of some aspects of attention, thus auditory attention may be more susceptible to impairment after a left hemisphere stroke. Prosody, rhythm and pitch changes associated with spoken language may improve spoken language comprehension in persons with aphasia by recruiting intact cognitive abilities (e.g., attention and working memory) and their associated non-lesioned brain regions post-stroke. Therefore, Experiment 2 explored the relationship between cognition, two unique prosody manipulations, lesion location, and auditory sentence comprehension in persons with chronic stroke and matched-controls. The combined results from Experiment 2a and 2b indicate that stroke participants with better auditory orienting attention and a specific left fronto-parietal network intact had greater comprehension of sentences spoken with sentence prosody. For list prosody, participants with deficits in auditory executive control and/or short-term memory and the left angular gyrus and globus pallidus relatively intact, demonstrated better comprehension of sentences spoken with list prosody. Overall, the results from Experiment 2 indicate that following a left hemisphere stroke, individuals need good auditory attention and an intact left fronto-parietal network to benefit from typical sentence prosody, yet when cognitive deficits are present and this fronto-parietal network is damaged, list prosody may be more beneficial.Dissertation/ThesisDoctoral Dissertation Speech and Hearing Science 201

An Investigation of the Relationship of Student Performance on the Wisconsin Card Sorting Test with Other Clinical Measures

The Wisconsin Card Sorting Test (WCST) is widely used for neuropsychological assessment of executive functions. Although the literature notes that the WCST is a measure of abstract reasoning and cognitive flexibility, there has been little data relative to the constructs that are assessed when the test is used with children or to the relationship between WCST performance and performance on other child assessment tools. This study of 94 children and adolescents referred for psychological evaluations investigated the relationship between scores obtained on the WCST and scores from child and adult versions of the Wechsler intelligence scales and the Delis-Kaplan Executive Function System, and selected Scale scores from the Behavior Rating Inventory of Executive Functions and the Behavior Assessment System for Children, based on ratings obtained from parents and teachers. The results suggest a modest relationship between WCST scores and the scores from other cognitive tests and rating scales, although students generally received higher Wechsler Matrix Reasoning scores than WCST Conceptual Level Response scores. In reviewing the performance of these 94 students, results also suggest differences in performance, based on test administration format (computer or manual) and by age groupings, with older students outperforming younger in spite of age-corrected scores. Analysis of response patterns, particularly the number of trials to complete the second set, and of performance observations suggest that use of a process approach may be helpful in identifying set-shifting and sustained attention difficulties of students not otherwise identified, using the existing WCST scoring procedures. This study suggests that the WCST may offer unique and important insights into the executive function capacities of children and adolescents

Methodological Artefacts in Consciousness Science

Consciousness is scientifically challenging to study because of its subjective aspect. This leads researchers to rely on report-based experimental paradigms in order to discover neural correlates of consciousness (NCCs). I argue that the reliance on reports has biased the search for NCCs, thus creating what I call 'methodological artefacts'. This paper has three main goals: first, describe the measurement problem in consciousness science and argue that this problem led to the emergence of methodological artefacts. Second, provide a critical assessment of the NCCs put forward by the global neuronal workspace theory. Third, provide the means of dissociating genuine NCCs from methodological artefacts

Neurobiological bases of intertemporal choices: A comprehensive review

Intertemporal choices (ICs) are choices that involve trade-off between costs and benefits that take place at differ ent moments in time. The aim of this article is to present a comprehensive literature review on neurobiological bases of IC. We present the functional models of IC and data from neuroimaging studies, namely ALE analysis. With this paper we intended to show the presence of immediate value preference beyond that predicted by a single-parameter exponential discounting model and its mapping to the dual-systems model for brain function. Studies indicate that individuals tend to show inconsistent preferences depending on the time until the rewards are available and support a perspective that intertemporal evaluation reflects neural mechanisms that differ from other forms of choice, although associated value signals are later represented in the context of a common reward system. The IC induces activations in a “nuclear network” and auxiliary areas including inferior prefrontal cortex, medial prefrontal cortex, temporo-parietal cortex, and peri-splenial posterior cingulate. The network of areas sensitive to value is comprised of several regions that include ventral striatum, medial prefrontal cortex, orbitofrontal cortex, and anterior insula. Evidence from neuroimaging and EEG studies corroborates that choices are determined by a dual evaluation system.info:eu-repo/semantics/publishedVersio

rTMS evidence for a dissociation in short-term memory for spoken words and nonwords

Differing patterns of verbal short-term memory (STM) impairment have provided unique insights into the relationship between STM and broader language function. Lexicality effects (i.e., better recall for words than nonwords) are larger in patients with phonological deficits following left temporoparietal lesions, and smaller in patients with semantic impairment and anterior temporal damage, supporting linguistic accounts of STM. However, interpretation of these patient dissociations are complicated by (i) non-focal damage and (ii) confounding factors and secondary impairments. This study addressed these issues by examining the impact of inhibitory transcranial magnetic stimulation (TMS) on auditory-verbal STM performance in healthy individuals. We compared the effects of TMS to left anterior supramarginal gyrus (SMG) and left anterior middle temporal gyrus (ATL) on STM for lists of nonwords and random words. SMG stimulation disrupted nonword recall, in a pattern analogous to that observed in patients, compatible with a role for this site in processing speech sounds without support from long-term lexical-semantic representations. Stimulation of ATL, a semantic site, disrupted the recall of words but not nonwords. A visual pattern memory task indicated that these effects of TMS were restricted to the verbal domain. These data provide convergent evidence for the conclusions of neuropsychological studies that support linguistic accounts of verbal STM

Learning, Arts, and the Brain: The Dana Consortium Report on Arts and Cognition

Reports findings from multiple neuroscientific studies on the impact of arts training on the enhancement of other cognitive capacities, such as reading acquisition, sequence learning, geometrical reasoning, and memory