Diane Swick - US grants

The primary goal of this proposal is to provide further insight into the brain regions responsible for implicit and explicit memory in the verbal domain and lexical-semantic processing at the level of single words. The project will utilize a combined neuropsychological and event-related brain potential (ERP) approach to illuminate controversies surrounding the location and duration of repetition and semantic priming effects, the time course of memory encoding and retrieval, and the nature of conceptual memory stores (i.e., amodal or modality specific). Our previous studies suggested that both left and right inferior temporal- occipital regions are critical for visual word priming. Other results demonstrated that damage to inferior prefrontal cortex and adjacent regions produces significant impairments in lexical-semantic processing and reductions in the amplitude of ERPs observed in a lexical decision task. In the current proposal, we will study groups of patients with defined deficits in memory or language abilities. These patients have focal, MRI-confirmed lesions in subregions of (1) prefrontal cortex, (2) temporal-parietal junction, (3) inferior temporal-occipital extrastriate regions, or (4) hippocampal formation. Two sets of experiments are proposed: (1) Behavioral and ERP studies in controls and patients will systematically examine the neuroanatomical and neurophysiological substrates of implicit and explicit memory; (II) Behavioral and ERP studies of semantic priming for words and pictures will compare lexical and conceptual processing in patients with and without aphasia. This project will provide a wealth of data on the neuroanatomical and elecrophysiological substrates of memory and semantic processing, which are essential for a greater understanding of how these operations are affected by aging, psychiatric and neurodegenerative diseases, and neurological insults. The pattern of spared cognitive abilities in these patients is of great interest with future applications in the development of improved rehabilitation strategies.

Brain Systems for Regulating Responses to Cognitive and Affective Conflict
Abstract
With National Science Foundation support, Dr. Swick will conduct a three-year study using psychological and ERP studies of neurological patients and healthy controls to investigate the roles of lateral preprefrontal, anterior cingulate, and orbitofrontal cortices in regulating responses to cognitive and affective conflict. Attentional control over behavior or executive control, is an important theoretical issue in cognitive neuroscience. Goal-directed behavior requires flexible adjustments of performance tailored to the current context. Our real world environment is saturated with stimuli varying in emotional significance, each associated with different courses of action. One important executive function is control over the response selection process in the face of conflicts among competing alternatives. Another crucial executive function is the ability to inhibit responses when they are no longer appropriate. Separate control systems for cognitive and affective processing can be distinguished, with the former mediated by lateral prefrontal cortex (LAT) and dorsal anterior cingulate cortex (ACC), and the latter by ventromedial prefrontal cortex (orbitofrontal cortex, or OFC, and ventral ACC). Although these systems may be relatively dissociable in the frontal lobes, cognitive and affective control processes typically interact to influence behavior under normal circumstances.
This proposal is guided by four major hypotheses: (1) LAT is essential for detecting response conflicts in cognitive tasks that involve either neutral or emotionally salient stimuli. (2) LAT signals dorsal ACC regions, which are implicated in the resolution (but not detection) of response conflicts. (3) OFC and ventral ACC are recruited only when the cognitive task contains emotional stimuli. (4) LAT is not critical for the regulation of affective conflict in the absence of response conflict. The proposed experiments will use a combined electrophysiological (event-related potential, or ERP) and neuropsychological approach. Patients with focal lesions in either AT, dorsal ACC, or OFC will be tested in a series of attentionally demanding tasks with words and faces that are emotional or neutral in valence. A set of six experiments is proposed to address the three Specific Aims of this project:
(1) To examine whether separate regions of the frontal lobes are specialized for the selection of different classes of stimuli. Exps. 1A-1C will examine different levels of conflict (lexical, semantic, emotional, or response-level) in color word and emotional Stroop interference tasks to ask the following questions: (A) Are separate regions of the frontal lobes specialized for the inhibition of different irrelevant stimulus dimensions, or do the same regions mediate selection regardless of stimulus type? (B) Is the left inferior frontal gyrus critical for suppressing irrelevant semantic input? (C) Is the dorsal ACC specifically associated with response conflict, and the OFC and ventral ACC with emotional conflict? (D) Do OFC patients have an enhanced attentional bias towards threatening faces? (E) Are there any left/right asymmetries of function in patients with unilateral lesions?
(2) To examine the neural substrates of interference effects in response selection tasks, and how these processes may be modulated by the emotional significance of the stimuli. Exps. 2A & 2B will use the flanker interference task with letters, neutral faces, or emotional faces as stimuli to address the following questions: (A) Do response conflicts with non-emotional stimuli engage executive control mechanisms in LAT, but not OFC? (B) Will executive control mechanisms in OFC be recruited when emotionally salient stimuli are used? (C) How does valence exert an influence on cognitive task performance? (D) The relative timing of conflict detection processes will be measured by the N450 ERP component.
(3) To examine the neural substrates of response inhibition and how it may be modulated by the emotional significance of the stimuli. Exp. 3 is a response inhibition (Go/NoGo) task using emotional and neutral words as stimuli that is designed to (A) measure the electrophysiological changes associated with response inhibition; (B) use the NoGo N2 ERP component as a sensitive measure for the time at which valence information is accessed; (C) determine whether separable regions are recruited for the selection (Go) and inhibition (NoGo) of responses to emotional vs. non-emotional stimuli; and (D) assess the effects of focal frontal lesions on the NoGo N2 component.
The broader impacts of this work on society are threefold: (1) The results have the potential to improve rehabilitation techniques in patients with frontal lobe injury. (2) Every effort will be made to include underrepresented minority students as participants in research with rare neurological populations. (3) Community-based talks at hospitals and senior centers will describe, in an accessible way, recent research on human brain function and how strokes and head injuries can affect these processes.