Byeongwook Lee

All Publications

• Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network. Nature communications Menon, V., Cerri, D., Lee, B., Yuan, R., Lee, S. H., Shih, Y. I. 2023; 14 (1): 866

  Abstract

  The salience network (SN) and default mode network (DMN) play a crucial role in cognitive function. The SN, anchored in the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, the causal neural mechanisms underlying changes in DMN activity and its functional connectivity with the SN are poorly understood. Here we combine feedforward optogenetic stimulation with fMRI and computational modeling to dissect the causal role of AI neurons in dynamic functional interactions between SN and DMN nodes in the male rat brain. Optogenetic stimulation of Chronos-expressing AI neurons suppressed DMN activity, and decreased AI-DMN and intra-DMN functional connectivity. Our findings demonstrate that feedforward optogenetic stimulation of AI neurons induces dynamic suppression and decoupling of the DMN and elucidates previously unknown features of rodent brain network organization. Our study advances foundational knowledge of causal mechanisms underlying dynamic cross-network interactions and brain network switching.

  View details for DOI 10.1038/s41467-023-36616-8

  View details for PubMedID 36797303

  View details for PubMedCentralID 2899886

• Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli. Science advances Chao, T. H., Lee, B., Hsu, L. M., Cerri, D. H., Zhang, W. T., Wang, T. W., Ryali, S., Menon, V., Shih, Y. I. 2023; 9 (7): eade5732

  Abstract

  The default mode network (DMN) is critical for self-referential mental processes, and its dysfunction is implicated in many neuropsychiatric disorders. However, the neurophysiological properties and task-based functional organization of the rodent DMN are poorly understood, limiting its translational utility. Here, we combine fiber photometry with functional magnetic resonance imaging (fMRI) and computational modeling to characterize dynamics of putative rat DMN nodes and their interactions with the anterior insular cortex (AI) of the salience network. Our analysis revealed neuronal activity changes in AI and DMN nodes preceding fMRI-derived DMN activations and cyclical transitions between brain network states. Furthermore, we demonstrate that salient oddball stimuli suppress the DMN and enhance AI neuronal activity and that the AI causally inhibits the retrosplenial cortex, a prominent DMN node. These findings elucidate the neurophysiological foundations of the rodent DMN, its spatiotemporal dynamical properties, and modulation by salient stimuli, paving the way for future translational studies.

  View details for DOI 10.1126/sciadv.ade5732

  View details for PubMedID 36791185

• Dopaminergic medication normalizes aberrant cognitive control circuit signalling in Parkinson's disease. Brain : a journal of neurology Cai, W., Young, C. B., Yuan, R., Lee, B., Ryman, S., Kim, J., Yang, L., Henderson, V. W., Poston, K. L., Menon, V. 2022

  Abstract

  Dopaminergic medication is widely used to alleviate motor symptoms of Parkinson's disease (PD), but these medications also impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication impacts cognition and working memory in PD by modulating frontoparietal-basal ganglia cognitive control circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual differences in response to dopaminergic medication. Here we use a novel state-space computational model with ultra-fast (490 msec resolution) fMRI to investigate dynamic causal signalling in frontoparietal-basal ganglia circuits associated with working memory in 44 PD patients ON and OFF dopaminergic medication, as well as matched 36 healthy controls. Our analysis revealed aberrant causal signaling in frontoparietal-basal ganglia circuits in PD patients OFF medication. Importantly, aberrant signaling was normalized by dopaminergic medication and a novel quantitative distance measure predicted individual differences in cognitive change associated with medication in PD patients. These findings were specific to causal signaling measures, as no such effects were detected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal causal signaling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in PD. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working memory load and the strength of load-dependent causal weights was not related to individual differences in working memory task performance in PD patients OFF medication. However, dopaminergic medication in PD patients reinstated the relation with working memory performance. Our findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify mechanisms by which dopaminergic medication normalizes cognitive control circuits.

  View details for DOI 10.1093/brain/awac007

  View details for PubMedID 35357463

• Latent brain state dynamics and cognitive flexibility in older adults. Progress in neurobiology Lee, B., Cai, W., Young, C. B., Yuan, R., Ryman, S., Kim, J., Santini, V., Henderson, V. W., Poston, K. L., Menon, V. 2021: 102180

  Abstract

  Cognitive impairment in older adults is a rapidly growing public health concern as the elderly population dramatically grows worldwide. While it is generally assumed that cognitive deficits in older adults are associated with reduced brain flexibility, quantitative evidence has been lacking. Here, we investigate brain flexibility in healthy older adults (ages 60-85) using a novel Bayesian switching dynamical system algorithm and ultrafast temporal resolution (490msec) whole-brain fMRI data during performance of a Sternberg working memory task. We identify latent brain states and characterize their dynamic temporal properties, including state transitions, associated with encoding, maintenance, and retrieval. Crucially, we demonstrate that brain inflexibility is associated with slower and more fragmented transitions between latent brain states, and that brain inflexibility mediates the relation between age and cognitive inflexibility. Our study provides a novel neurocomputational framework for investigating latent dynamic circuit processes underlying brain flexibility and cognition in the context of aging.

  View details for DOI 10.1016/j.pneurobio.2021.102180

  View details for PubMedID 34627994