Clinical, Cognitive, Faculty, Neuroscience
Dr. Wen Li
Northwestern University, 2004
Associate Professor
Our research goal is to understand sensory and perceptual anomalies in anxiety disorders and to develop novel behavioral and neural interventions targeting sensory/perceptual roots of various anxiety pathologies. Our multi-disciplinary research integrates clinical psychology, cognitive, and affective neuroscience, adopting multi-modal methodologies such as psychophysics, psychophysiology, fMRI, EEG, and transcranial electrical stimulation (tES).
Anxiety disorders, cognition, emotion, and neuroscience
Research Description
How do people extract emotional meaning from an environmental input and respond with fear, anger or joy? Focusing on threat-relevant emotions, we approach this question from a neurosensory perspective (i.e., sensory-cortex-based threat encoding): The sensory cortex stores threat codes and thus supports active, independent encoding of threat cues during sensory processing, initiating defensive responses directly or interactively with the limbic system (Clancy et al., 2017; Li, 2014; Krusemark & Li, 2013). This sensory mechanism provides an additional pathway to threat processing beyond the limbic system, while making clear evolutionary sense by permitting categorization of biological significance of an environmental input in the initial sensory analysis, prompting people to respond with minimal delay. Furthermore, in individuals with high levels of anxiety or anxious predispositions, sensory cortical encoding of threat could be exaggerated, and combined with limbic hyperreactivity to threat and inadequate prefrontal inhibition thereof, these processes can contribute to a vicious cycle, accounting for the genesis and maintenance of pathological anxiety.
Using a combination of tools and techniques (fMRI, EEG/MEG, psychophysiology and psychophysics), our research proceeds in four directions: (1) proposing a neurosensory mechanism of threat encoding (and anxiety) that expands the existing models; (2) identifying the signature of sensory-cortical encoding of threat (in anxiety); (3) identifying sensory cortical plasticity induced by aversive learning as a mechanism underlying the formation and maintenance of threat codes in the sensory cortex; and (4) examining sensory cortical plasticity as a result of perceptual training and transcranial electrical stimulation, thereby rewriting or erasing threat codes or adjusting neural excitability in the sensory cortex to reduce fear responses and anxiety symptoms.
Selected Publications
You, Y., Novak, L. R., Clancy, K., & Li, W. (2022). Pattern differentiation and tuning shift in human sensory cortex underlie long-term threat memory. Current Biology, 32(6).
Clancy, K. J., Andrzejewski, J. A., You, Y., Rosenberg, J. T., Ding, M., & Li, W. (2022). Transcranial stimulation of alpha oscillations up-regulates the default mode network. Proceedings of the National Academy of Sciences, 119(1), e2110868119. doi:10.1073/pnas.2110868119
You, Y., Brown, J., & Li, W. (2021). Human sensory cortical contributes to the long-term storage of aversive conditioning. The Journal of Neuroscience(14), 3222-3233. doi:10.1523/jneurosci.2325-20.2021
Li, W. (2019). Basic Mechanisms in Fear and Anxiety—Perception. In B. Olatunji (Ed.), The Handbook of Anxiety and Related Disorders. New York: Oxford University Press.
Clancy, K., Ding, M., Bernat, E., Schmidt, N. B., & Li, W. (2017). Restless 'rest': intrinsic sensory hyperactivity and disinhibition in post-traumatic stress disorder. Brain, 140(7), 2041-2050. doi:10.1093/brain/awx116
Krusemark, E. A., & Li, W. (2013). From early sensory specialization to later perceptual generalization: dynamic temporal progression in perceiving individual threats. J Neurosci, 33(2), 587-594. doi:10.1523/JNEUROSCI.1379-12.2013
Krusemark, E. A., Novak, L. R., Gitelman, D. R., & Li, W. (2013). When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation. J Neurosci, 33(39), 15324-15332. doi:33/39/15324
Krusemark, E. A., & Li, W. (2011). Do all threats work the same way? Divergent effects of fear and disgust on sensory perception and attention. J Neurosci, 31(9), 3429-3434. doi:10.1523/JNEUROSCI.4394-10.2011
Li, W., Howard, J. D., Parrish, T. B., & Gottfried, J. A. (2008). Aversive learning enhances perceptual and cortical discrimination of indiscriminable odor cues. Science, 319(5871), 1842-1845. doi:10.1126/science.1152837