Hakwan Lau - US grants

DESCRIPTION (provided by applicant): Humans are able to reflect upon ongoing cognition, an ability known as metacognition. Metacognition can be measured as one's ability to introspectively distinguish between effective and ineffective cognitive processing, for instance, by rating confidence to distinguish between correct and incorrect trials in a task. In this project we have two specific aims. First, we try to address the question of whether there is a single common mechanism for metacognition across different task modalities (e.g., memory and vision), or specific independent, domain C specific mechanisms. We take an individual differences approach to investigate the structural brain differences (assessed via structural magnetic resonance imaging, MRI) that facilitate metacognitive efficiency. We develop original psychophysical measurements to quantify an individual s metacognitive efficiency, and investigate the neural bases for metacognition in both verbal memory and visual perception. We measure metacognition in two tasks (memory and vision) and apply structural equation modeling (SEM) to analyze anatomical variability in healthy individuals. We test hypotheses regarding which brain regions facilitate metacognitive efficiency generated from these analyses in patients with lesions in those target regions. Second, we investigate the functional mechanisms supporting metacognition in order to explain, and investigate why normal human subjects often do not perform at optimal levels in metacognitive tasks. There are likely two sources of such suboptimalities. On the sensory side, we test a model according to which perceptual confidence is heuristically based on only part of the perceptual signal. We test this by using intracranial electrocortigraphy (ECoG) in human (surgical epileptic) subjects. On the response output side, one candidate model suggests that subjects evaluate the efficacy of their cognitive processes based on retrospective monitoring of their behavioral response systems. If this model is correct, then subjective confidence may depend on the level of noise or conflict evoked in the motoric response system as perceptual judgments are formed. We test this model by directly injecting noise into the motor system at different times during a perceptual task via transcranial magnetic stimulation (TMS). This project is timely as it involves testing novel hypotheses about metacognitive mechanisms, inspired by recent studies and our own preliminary findings. Some of these tests are also only made possible due to our development of novel psychophysical and modeling approaches, which will be of use to other researchers in the field. Finally, the use of neuropsychology, TMS, and intracranial electrophysiology to test formal models of the functional mechanisms of metacognition will help us to arbitrate between existing views in the literature, which, in human studies, currently remains largely confined to behavioral rather than neurobiological investigations. Our project will help to bridge the gap between these two related fields, fostering the development of a mechanistic account of metacognition that can inform clinical and everyday applications (such as cognitive training).

PROJECT SUMMARY The objective of this application is to use the novel approach of neuro-reinforcement based on decoded fMRI information to reduce fear responses to fearful stimuli (e.g., spiders, heights) in individuals with phobias, directly and unconsciously in the brain, without repeatedly exposing participants to their feared stimuli. The Specific Aims of the R61 Phase are to: (1) confirm that our method engages the neurobiological target (amygdala reactivity to images of a feared object) in a population of individuals with specific phobia; and (2) to determine dosage-response optimization. The Specific Aims of the R33 Phase are to: (1) quantify how changes in amygdala reactivity with neuro-reinforcement covary with changes in behavioral, subjective, and physiological outcomes in the same context as the treatment; and (2) determine how engagement of the neurobiological target and related effects in subjective fear ratings and physiological outcomes generalize to new contexts and clinically relevant outcomes. Pilot Data demonstrate that the proposed method can effectively reduce amygdala reactivity to feared stimuli (target engagement). The R61 Phase will confirm engagement of the neurobiological target (amygdala reactivity to fearful stimuli) by our intervention method in patients suffering from phobia of everyday objects and animals (e.g., spiders). Varying the number of neuro- reinforcement sessions across different subject groups (3 groups of 10 subjects each) and measuring reductions in the amygdala reactivity will demonstrate the robustness and mechanisms of target engagement. This will also enable assessment of the optimal dosage required to balance between maximal target engagement and imaging costs, in order to inform the studies in the R33 Phase. The R33 Phase will utilize the optimal dosage determined in the R61 Phase to test mediation of clinically relevant outcomes (clinical diagnostic interviews, subjective fear ratings, and skin conductance) by engagement of the neurobiological target, both immediately after treatment and after a 4-month period. The R33 Phase will further assess whether the effects generalize to a clinically relevant measure of phobic individuals' readiness to approach the feared objects in a virtual environment (Behavioral Approach Test).