Doctor of Philosophy, Korea Advanced Institute Of Science and Technology (2019)
Ph.D., Korea Advanced Institute of Science and Technology (KAIST), Bio and Brain Engineering (2019)
B.S., Korea Advanced Institute of Science and Technology (KAIST), Electrical Engineering (2011)
Vinod Menon, Postdoctoral Faculty Sponsor
Dopaminergic medication normalizes aberrant cognitive control circuit signalling in Parkinson's disease.
Brain : a journal of neurology
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
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